Review

Quorum sensing in Acinetobacter: with special emphasis on antibiotic resistance, biofilm formation and quorum quenching

  • Acinetobacter is an important nosocomial, opportunistic human pathogen that is gradually gaining more attention as a major health threat worldwide. Quorum sensing (QS) is a cell-cell communication system in which specific signaling molecules called autoinducers accumulate in the medium as the population density grows and control various physiological processes including production of virulence factors, biofilm and development of antibiotic resistance. The complex QS machinery in Acinetobacter is mediated by a two-component system which is homologous to the typical LuxI/LuxR system found in Gram-negative bacteria. This cell signaling system comprises of a sensor protein that functions as autoinducer synthase and a receptor protein which binds to the signal molecules, acyl homoserine lactones inducing a cascade of reactions. Lately, disruption of QS has emerged as an anti-virulence strategy with great therapeutic potential. Here, we depict the current understanding of the existing QS network in Acinetobacter and describe important anti-virulent strategies developed in order to effectively tackle this pathogen. In addition, the prospects of quorum quenching to control Acinetobacter infections is also been discussed.

    Citation: Bindu Subhadra, Man Hwan Oh, Chul Hee Choi. Quorum sensing in Acinetobacter: with special emphasis on antibiotic resistance, biofilm formation and quorum quenching[J]. AIMS Microbiology, 2016, 2(1): 27-41. doi: 10.3934/microbiol.2016.1.27

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  • Acinetobacter is an important nosocomial, opportunistic human pathogen that is gradually gaining more attention as a major health threat worldwide. Quorum sensing (QS) is a cell-cell communication system in which specific signaling molecules called autoinducers accumulate in the medium as the population density grows and control various physiological processes including production of virulence factors, biofilm and development of antibiotic resistance. The complex QS machinery in Acinetobacter is mediated by a two-component system which is homologous to the typical LuxI/LuxR system found in Gram-negative bacteria. This cell signaling system comprises of a sensor protein that functions as autoinducer synthase and a receptor protein which binds to the signal molecules, acyl homoserine lactones inducing a cascade of reactions. Lately, disruption of QS has emerged as an anti-virulence strategy with great therapeutic potential. Here, we depict the current understanding of the existing QS network in Acinetobacter and describe important anti-virulent strategies developed in order to effectively tackle this pathogen. In addition, the prospects of quorum quenching to control Acinetobacter infections is also been discussed.


    Since the terrorist attacks in the United States at September 11, 2001, great efforts have been made worldwide to improve the safety of public health and people's awareness of security threats. Many countries are increasingly concerned about water security, especially the threat of malicious terrorist attacks on water supplies. Water Distribution Network (WDN) has become one of the most important public facilities that are prone to accidents or deliberate pollution invasion due to its wide coverage and continuous open state [1]. Several large scale incidents of sudden drinking water pollution in recent years have warned us that these contamination incidents may lead to social health problems and have adverse political effects [2]. Therefore, drinking water early warning system is necessary to reduce the impact of sudden pollution incident.

    In a typical drinking water warning system, a large number of water quality monitoring sensors are deployed to detect contaminant [3,4,5]. Based on the sensing data, it is essential to identify the contaminant source, i.e., contaminant source identification [6,7,8]. Last, and also the most important, it is significant to take some actions to isolate the contaminant according to the emergency response policy [9].

    Upon the water pollution, one intuitive way to ensure the safety of people is to cut the supply of water in the whole WDN. However, this will lead to serious social and economic losses, or may even cause social panic. An alternative way is to well schedule the valves and hydrants in the WDN to ensure the contaminants are isolated, without incurring too much negative impact. By scheduling the valves, the contaminant water can be controlled within certain range; Furthermore, by scheduling the hydrants, it is able to discharge the contaminant in the WDN so as to recover the normal water supply as soon as possible. In this case, the problem is on how to schedule the valves and hydrants based on the water quality monitoring sensing data.

    For example, a simple typical water distribution network is shown in Figure 1. When contamination event occurs, there will be serious contamination diffusion if the valve is not timely and reasonably scheduled, as shown in the Figure 1(a). However, when a reasonable scheduling is performed, the contamination situation can be controlled as shown in Figure 1(b).

    Figure 1.  (a) Contaminant spreads without any response action; (b) Contaminant spreads with response actions.

    The scheduling of valves and hydrants for contaminant isolation actually has been widely studied. Various optimization algorithms have been applied [10,11], such as genetic algorithm [12] and ant colony algorithm [13]. These heuristic algorithms have the advantages of easy implementation, but they suffer from complex parameter adjustment, hindering their practical adoption. Most importantly, these heuristic algorithms require precise contamination source information for subsequent scheduling computation, which means that the timeliness of the scheduling is ignored due to the calculation of precise location of contamination source. Fortunately, we notice that the success of AlphaGo [14] has raised many interests in both academic and industry. The core of AlphaGo is deep reinforcement learning, which has been widely applied in vast domains, e.g., intelligent transportation control, computer game, robotics control, etc [15,16]. By studying these applications, we find that deep reinforcement learning is quite appropriate to be applied for the real time scheduling of valves and hydrants for contaminant isolation in WDN. Therefore, we are motivated to investigate this issue in this paper.

    The main contributions of this paper are as follows:

    We accurately model the valve and hydrant scheduling problem to fit the reinforcement learning framework. In particular, we treat the sensing data in the WDN as the state, and the valve and hydrant scheduling as the action. Compared with traditional optimization algorithm, our method can model various uncertain contamination scenarios without accurately characterizing the contamination sources, which obey the timeliness principle of emergency scheduling task. By training the scheduling agent offline and deploying them online, real time scheduling can be achieved. To our best knowledge, this is the first work that applies reinforcement learning in valve and hydrant scheduling.

    We use open source simulator EPANET to evaluate the efficiency of our algorithm. Extensive simulation results show that our reinforcement learning based method can well schedule the valve and hydrant to effectively isolate the contaminant.

    The rest of this paper is structured as follows. Section 2 presents some related work on the scheduling of valves and hydrants in WDN, as well as some preliminaries on reinforcement learning and its applications. Then, Section 3 elaborates and formulates the valves and hydrants scheduling problem. Section 4 gives our reinforcement learning based scheduling algorithm and Section 5 shows simulation based performance evaluation results. Finally, Section 6 concludes the paper.

    The scientific community has devoted a great deal of effort to developing sensor-based contaminant warning systems (CWS) that deploy water quality monitoring sensors in WDN to identify contaminant sources [4,17]. Most of the previous studies focused on improving the ability of CWS to quickly identify the contaminant source and to increase the reliability of the monitoring system. For example, some new forms of sensors are invented and applied in the WDN [18], especially the mobile sensors, which can flow in the water pipes and move very close to leakage point. As a result, it is reported that the detection accuracy is higher than the traditional static sensors [19]. Once the water quality monitoring sensors detect contamination, we shall identify the contaminant source to derive where, when and how much the contaminant are inject into the WDN. Afterwards, emergency response mechanisms will give a series operations on valves and hydrants to evacuate the contaminated water [20]. Once an effective response policy is adopted, the impact of pollution can be minimized and the water supply system can be recovered to normal running status [21].

    By literature survey, we notice that many studies formulate the contaminant source identification and scheduling problems as single objective or multi-objective optimization problems. Regarding the emergency response problem to contamination events in WDNs, the basic optimization goal is to minimize the impact resulting from the contamination. For example, Poulin et al. [22] proposed an emergency response strategy to ensure drinking water safety in which the operational sequence of valves and hydrants was determined with the objective of minimizing the amount of contaminated water consumed. Later on, they further [23] considered the combination of valves and hydrants, and proposed a new operation policy of unidirectional flushing for the contaminated water. In 2012, Gavanelli et al. [24] optimized the scheduling of a set of tasks by genetic algorithm so that the consumed volume of the contaminated water is minimized. In addition to considering the operation of valves and hydrants, there are also some other actions that can be used to minimize the impact on public health. For example, the use of dye injection can act as an alert mechanism, which can discourage the public consumption of potentially contaminated water [25].

    Although much of the research in this field considered the scheduling of valves and hydrants as a single objective optimization problem, it inherently involves multiple objectives such as system design costs, operation costs, water quality, and others. Accordingly, some multi-objective optimization algorithms have been proposed in some recent studies [9,12]. Rasekh et al. [26] proposed a simulation framework via social risk assessment to simulate the dynamics of pollution events by assuming relaxed static, homologous and static responses in traditional engineering methods. They established a multi-objective model and used genetic algorithm approach to trade off the consequences and the probability of occurrence. Afshar et al. [13] propose an ant colony optimization based algorithm, coupled with the WDN simulator EPANET, to minimize the maximum regret and the total regret by selecting the best combination of hydrants and valves. Rasekh et al. [27] propose a contaminant response mechanism where the disposals are optimized using evolutionary algorithms to achieve public health protection with minimum service interruption.

    We notice that the optimization algorithms can achieve good performance under deterministic environment. Otherwise, it is hard to achieve better results in dynamic or uncertain environment. For example, it challenges to design optimization algorithm to schedule valves and hydrants when water demand varies which thus leads to the change of flow speed and direction. In some extreme cases, we even cannot identify the location of contaminant source by little sensor data. In these situations, reinforcement learning can be used to schedule the valves and hydrants by reading the information from the sensors.

    Reinforcement learning has been widely applied to scheduling problems in many other disciplines. For example, Knowles et al [28] use reinforcement learning to improve long term reward for a multistage decision based on feedback given either during or at the end of a sequence of actions. Yau et al [29] present an extensive review on the application of the traditional and enhanced reinforcement learning to various types of scheduling schemes, namely packet, sleep-wake and task schedulers, in wireless networks, as well as the advantages and performance enhancements brought about by reinforcement learning. In order to overcome the challenges of implementing dynamic pricing and energy consumption scheduling, Kim et al. [15] propose a reinforcement learning algorithm that allows each of the service provider and the customers to learn its strategy without a priori information about the micro-grid in electricity grid. Moghadam et al. [16] propose a two-phase reinforcement learning-based algorithm for data-intensive tasks scheduling in cluster-based data grids. These aforementioned studies show that reinforcement learning is an effective alternative for solving scheduling problem. Although with great success in different domains, none of existing studies applies reinforcement learning to solve the contaminant isolation problem via the scheduling of valves and hydrants. We are motivated to address this issue in this paper.

    To ensure the safety of consumers, it is crucial to monitor water quality and operate the valves or the hydrants. In recent years, the SCADA (Supervisory Control And Data Acquisition) system has been widely deployed for water distribution to facilitate water management. Smart water management mainly includes two functions, one is to monitor portable water, the other is aiming to monitor the water supply distribution, which includes control water flow, speed, rate and tubes conditions.

    In a smart water distribution management system, the components includes pipes, valves, reservoirs and clean water pumping stations. The sensors are deployed at any nodes to collect monitoring data of these component. Figure 2 shows a general water distribution architecture, which consists of three layers which are WSN (Wireless Sensor Network) layer, IoT Layer and Cloud layer.

    Figure 2.  A typical architecture of Water distribution management.

    In the WSN layer, sensors are deployed to measure the contaminant concentration and flow data. These continuous level sensors transmit data through a wireless network to a base station. Then, the base station sends the data to the cloud by the Ethernet connection. Programable Logical Controller (PLC) is used to open or close electric valves, thus change the flow direction in WDS.

    IoT layer mainly provides WDS with the connectivity which allow sensors and valves to connect to cloud layer. As a bridge between WSN Layer and Cloud Layer, the IoT layer permits the control between valves and PLC, also send the data captured by sensors to cloud layers.

    In the cloud layer, user can be aware of water quality and avoid accidental contamination. The authority can make a good decision directly by intelligence computation when sudden water incidents happen.

    Water distribution systems, which consist of thousands of pipes, junctions and hydro-valves, may be of loop or branch network topologies, or a combination of both. They are often modelled as a graph $ G = (V, E) $, where vertices in $ V $ represent junctions, tanks, hydrants or other sources, and edges in $ E $ represent pipes and valves. The flow of drinking water depends on demand and pumping capacity, both of which may vary frequently.

    There are $ H $ hydrants, $ N $ valves and $ M $ sensors in WDS. Once any contaminant event occurs, sensors may take an alarm when the contaminated water pass by. We need to give an optimal scheduling policy $ \pi $ of hydrants and valves at a period $ T $, thus to maximize disposal of contaminated water as soon as possible, so the performance index can be formulated as Eq (3.1):

    $ F=maxTt=1Hh=1Dh(π(st)).
    $
    (3.1)

    Here, $ D_h(\pi) $ is the disposal of $ h $-th hydrant under policy $ \pi $ and $ \pi(s_t) $ is the scheduling policy of hydrants and valves for state $ s $ at time $ t $. The disposal $ D $ can be simulated by a open source software named EPANET [30]. $ s_t $ is a state tensor of sensor readings which can be represented by

    $ {e1,e2,,eM}
    $
    (3.2)

    Here, $ e_m $ is a continuous value acquired from sensor $ m $, because real value reading sensors which can get more information of contamination event is used in our algorithm rather than discrete value reading sensors.

    Policy $ \pi $ is a function of state $ s $, and its value is an action $ a $ for a certain state $ s_t $ that can be defined as a tensor:

    $ a={v1,v2,,vN,h1,h2,,hH}
    $
    (3.3)

    where $ v, h\in\{0, 1\} $ is the operation for valve and hydrant respectively in WDN. The action $ a $ for state $ s $ chosen from scheduling policy $ \pi $ is executed to open or close valves and hydrants.

    We can know from Eq (3.3) that there are $ 2^{N+H} $ possible actions. If we assume that the step between two actions in scheduling period $ T $ is $ stp $, the time complexity of enumeration method to exhaust the optimal solution of policy $ \pi $ is $ O(2^{(N+H)*T/stp}) $. It's challenging to search the optimal solution in a large WDN with many valves and hydrant.

    For the ease of reading, Table 1 summarizes the abbreviations of above technical terms.

    Table 1.  Notations.
    $G$A graph is modeled by a WDN
    $V$V represents junctions, tanks, hydrants or other sources
    $E$E represents pipes and valves
    $H$Number of hydrant
    $N$Number of valve
    $M$Number of sensor
    $\pi$Scheduling policy function
    $T$Scheduling period
    $s$State acquired from sensors in WDN
    $D$Disposal of contaminant
    $a$Action, a tensor composed of valve operations and hydrant operations

     | Show Table
    DownLoad: CSV

    When a water quality sensor rise an alarm, the control center need to develop an optimal scheduling of valves and hydrants to minimize the impact on the consumers in WDN. Scheduling of hydrant and valve can be carried out according to the monitoring data which collected from sensors. By scheduling valves in an appropriate sequence, we intend to isolate and evacuate contaminated water. Valve can be closed or open, resulting in drinking water-break partly, or limiting movement of contaminated water in WDN. Open hydrant is able to flush contaminants out of WDN. The aim of reducing the concentration of contaminants in WDN can be achieved by scheduling the valves to lead the contaminated water body to the open hydrant. The framework of scheduling algorithm is shown in the Figure 3.

    Figure 3.  Diagram of scheduling problem.

    Control center chooses an action from optimal scheduling policy which is pre-trained by deep learning algorithm proposed in this paper according to the real-time monitoring data collected by water quality sensors in WDN, and applies action to hydrants and valves. Control center will repeat the operation until the reading of water quality sensor shows that it is at the safe level.

    Reinforcement learning, distinguishing from supervised learning and unsupervised learning, focuses on the interaction between the reinforcement learning agent and the environment. Agent, as the core of reinforcement learning, obtains the optimal policy by keep learning through trial and error like humans in the different environments to pursue the optimal action, rather than directly be told what action should be done [31]. The principle of reinforcement learning is to learn how to maximize the long-term rewards through a sequence of trial actions. The challenging problem is that any action for a state not only affects the reward of the current state, but also the next state and the states thereafter in the long run. Therefore, it is essential to carefully choose the action for one state with the consideration of future possible states and rewards. Considering that the reading of the sensor is continuous value, we apply deep reinforcement learning [32] to give an optimal scheduling policy.

    We first represent the problem of scheduling valves and hydrants as a Markov Decision Processes (MDP), which is defined as a tuple $ (s, a, p, r) $. In the valves and hydrants scheduling problem, states $ s $, actions $ a $, transition probabilities $ p $ and rewards $ r $ are defined as follows:

    ● $ s $: a tensor which is made up of sensor readings.

    ● $ a $: a tensor which is made up of the operation of valves and hydrants.

    ● $ p $: a set of state transition probabilities. In this scheduling problem, the transition probability of the next state after an action is executed is unknown, so it is a model-free problem.

    ● $ r $: a reward function: $ r(s, a) $ is a real-valued immediate reward for taking action $ a $ in state $ s $. The goal of reinforcement learning is to enable the agent to continuously interact with the environment to learn an optimal policy, so as to obtain the maximum cumulative reward. We define the mass of contaminant disposal within the time step after each action taken as the reward value, which can be obtained by simulator EPANET.

    A MDP unfolds over a series of steps. At each step, the agent observes the current state, $ s $, chooses an action, $ a $, and then receives an immediate reward $ r(s, a) $ that depends on the state and action. The agent begins in the initial state $ s_0 $, which is assumed to be known. The states transit according to the distribution $ p $, which is hard to directly obtained, especially when the state dimension is large or the state value is continuous. Therefore, we rely on deep reinforcement learning to solve the model-free scheduling problem.

    We regard the control center in scheduling problem as an agent. The goal of the agent is to interact with the emulator (EPANET) by selecting actions in a way that maximises the future rewards (mass of contaminant disposal). We make the standard assumption that future rewards are discounted by a factor of $ \gamma $ per time-step, and define the future discounted return at time $ t $ as $ R_t = \sum^T_{t' = t}\gamma^{t'-t}r_{t'} $, where $ T $ is the scheduling period. We define the optimal action-value function $ Q^*(s, a) $ as the maximum expected return achievable by following any strategy, after seeing some sequence $ s $ and then taking some action $ a $, $ Q^*(s, a) = \max_\pi\mathbb{E}[R_t|s_t = s, a_t = a, \pi] $, where $ \pi $ is a policy mapping sequences to actions (or distributions over actions). The optimal action-value function obeys an important identity known as the $ Bellman \quad equation $. This is based on the following intuition: if the optimal value $ Q^*(s', a') $ of the sequence $ s' $ at the next time-step is known for all possible actions $ a' $, then the optimal strategy is to select the action $ a' $ maximising the expected value of $ r+\gamma Q^*(s', a') $,

    $ Q(s,a)=Esε[r+γmaxaQ(s,a)|s,a]
    $
    (4.1)

    It is common to use a function approximator to estimate the action-value function, $ Q^{(s, a; \theta)} \approx Q^*{(s, a)} $. Here we refer to a neural network function approximator with weights $ \theta $ as a Q-network. A Q-network can be trained by minimising a sequence of loss functions $ L_i(\theta_i) $ that changes at each iteration $ i $,

    $ Li(θi)=Es,aρ()[(yiQ(s,a;θi))2],
    $
    (4.2)

    where $ y_i = \mathbb{E}_{s'\sim\varepsilon}[r+\gamma \max_{a'} Q(s', a'; \theta_{i-1})|s, a] $ is the target for iteration $ i $ and $ \rho(s, a) $ is a probability distribution over sequences $ s $ and actions $ a $ that is generated by an $ \epsilon $-greedy strategy.

    We utilize a technique known as experience replay where we store the experiences of agent at each time-step, $ e_t = (s_t, a_t, r_t, s_{t+1}) $ in a data-set $ D = \{e_1, \ldots, e_N\} $, pooled over many episodes into a replay memory. During the inner loop of the algorithm, we apply Q-learning updates, or mini-batch updates, to samples of experience, $ e\sim D $, drawn at random from the pool of stored samples. After performing experience replay, the agent selects and executes an action according to an $ \epsilon $-greedy policy. It should be noticed that the experience with contamination source not detected is useless, which means we should not store the experience when the all the readings of sensors below safe threshold. In this case, we execute nothing as default if none contamination was detected by sensors within scheduling period $ T $. The customized deep Q-learning algorithm (CDQA), which is used to train a intelligent agent (control center), is presented in Algorithm 1.

    Algorithm 1 The customized deep Q-learning algorithm
      Initialize replay memory $D$ to capacity $N$;
      Initialize action-value function $Q$ network with random weights;
      for $episode\in[1, L]$ do
        Sample a random junction from WDN as a contamination source and generate a contamination event $e$;
        Observe the initial state $s_1$ according to the event $e$;
        for $t\in[1, T]$ do
          With probability $\epsilon$ select a random action $a_t$, otherwise select $a_t=\max_a Q^*(s_t, a; \theta)$;
          Execute action $a_t$ in simulator and observe reward $r_t$ and next state $s_{t+1}$;
          if contaminant concentration in $s_t$ is not less than safe threshold $\phi$ then
            Store transition $(s_t, a_t, r_t, s_{t+1})$ in $D$;
            Sample random mini-batch of transition $(s_j, a_j, r_j, s_{j+1})$ from $D$;
            Set $y_j=r_j+\gamma\max_{a'}Q(s_{j+1}, a'; \theta)$ for non-terminal $s_{j+1}$, or $y_j=r_j$ for terminal $s_{j+1}$;
            Perform a gradient descent step on $(y_j-Q(s_j, a_j; \theta))^2$;
          end if
        end for
      end for

    In practice, our algorithm only stores the last $ N $ experience tuples in the replay memory, and samples uniformly at random from $ D $ when performing updates. Our goal is to train an effective and general model which is independent of adjustment of the parameters for minimizing the impact of contaminant event in WDN. In Algorithm 1, the reason why we sample random contamination events from WDN is to train a general agent which is able to work well in most real contamination events. In other words, our agents may perform well without having to locate the source of the contamination, which takes a lot of online time of computation. There are two loops in CDQA, so the time complexity of our algorithm is $ O(L*T) $, where $ T $ is scheduling period and $ L $ is iterations. As the iterations $ L $ increases, the policy $ \pi $ given by agents trained by CDQA can approach the optimal solution. The performance of CDQA may depend on a very large $ L $, but our CDQA requires less time complexity than the enumeration method mentioned in Section 3. Considering the cost of online training is extremely expensive because of severity the of real contamination events, we train agent offline and test it in water quality simulator (EPANET).

    In order to demonstrate the ability of the agent trained by CDQA, two experiments with different number of contaminant scenario are performed. A real-world WDN [6,33] as depicted in Figure 4 are used to simulate in our experiments. The WDN includes 97 nodes, 3 of which are hydrants and 4 of which are sensors, 119 pipes, 3 of which are valves. Assuming that the maximum scheduling period $ T $ is 24 hours; Scheduling step is 30 minutes. The water demand of each hydrant is 400 gallons per minute. For each contamination event, contaminant is continuously injected into the node of WDN at the first hour. Noted valves (blue triangle) and hydrants (black square) are located in the pipelines and nodes respectively, and sensors (red triangle) are deployed at the nodes.

    Figure 4.  Four sensors (red triangle), three valves (blue triangle), and three hydrants (black square) are deployed in the WDN of 97 nodes.

    In the following experiments, initial discount factor $ \gamma $ is set to 0.5 and we use the Adam algorithm with mini-batches of size 32 to train the $ Q $ network. The behavior policy during training was $ \epsilon $-greedy with $ \epsilon $ annealed linearly from 1 to 0.1 over the half of training process and 0.1 over the other training process. We set episode iterations $ L $ to 5000 and capacity $ N $ of replay memory to 1000. Safe concentration $ \phi $ is set to 0.2 mg/L. The structure of $ Q $ network shown in Table 2 is a classical fully-connected network where there are 3 hidden layers, 1 input layer and 1 output layer. The input tensor is concatenation of action tensor $ a $ shown in Eq 3.3 and sensor reading tensor shown in Eq 3.2. The output is prediction of Q value.Gavanelli2012.

    Table 2.  Structure of $Q$ network.
    LayerUnitsActivation Function
    fully connected15ReLU
    fully connected6ReLU
    fully connected6ReLU
    fully connected1Linear

     | Show Table
    DownLoad: CSV

    In order to show the performance of agents in each episode, we apply EPANET to simulate two cases, one is that all the valves and hydrants are open, the other is that all the valves are closed and all the hydrants are open, then we can compute the mass of contamination disposal VOHO and VCHO, respectively.

    In this experiment, we test three single contaminant events which occur at the node SOURCE1, SOURCE2 and SOURCE3, respectively. The locations of contamination sources are marked with blue arrow in Figure 5. It is should be noticed that these test contaminant events are all chosen without deliberation. Each contamination events is evaluated in every episode of the algorithm.

    Figure 5.  Locations of contaminant event at the node SOURCE1, SOURCE2 and SOURCE3.

    Figure 6 shows how the mass of contaminants disposal evolves during training on the contamination events SOURCE1, SOURCE2 and SOURCE3. From the Figure 6, we can see that plots are not stable, but the algorithm tends to converge at the later stage of training. The most important thing is that the performance of our CDQA are much better than VOHO and VCHO performed on these three plots.

    Figure 6.  Plot (a), (b) and (c) show how the mass of contaminants disposal evolves during training on the contamination events SOURCE1, SOURCE2 and SOURCE3, respectively.

    We set the three contamination events used in the last experiment (SOURCE1, SOURCE2, and SOURCE3) to happen simultaneously as a test. Two new contamination events SOURCE4 and SOURCE5 are added as another test. Both tests are evaluated in every episode of the algorithm. The locations of the five contamination sources are marked with arrow in Figure 7.

    Figure 7.  The locations of contamination sources SOURCE1, SOURCE2, and SOURCE3 in the first test are marked with blue arrow and SOURCE4 and SOURCE5 in the second test are marked with red arrow.

    Figure 8 shows how the mass of contaminants disposal evolves during training on the contamination events where SOURCE1, SOURCE2 and SOURCE3 occur simultaneously and SOURCE4 and SOURCE5 occur simultaneously. As shown in the figure, the CDQA still has advantages over VOHO and VCHO because most of the points on the CDQA are above VOHO and VCHO.

    Figure 8.  The plot (a) shows the variation of the mass of contaminants disposal during training process when contamination events SOURCE1, SOURCE2 and SOURCE3 occur simultaneously. The plot (b) shows the variation of the mass of contaminants disposal when SOURCE4 and SOURCE5 occur simultaneously.

    In order to further explore the final performance of the agent trained by CDQA, we recorded the state within a scheduling period at the last episode of training process of CDQA, which is shown in Table 3. In this table, the mass of contaminant disposal is 23648 gram and the contamination event is that three contamination sources SOURCE1, SOURCE2 and SOURCE3 occur simultaneously. The locations of sensors, valves and hydrants were shown in Figure 4. The reading of Sensor2 is 264.842 at time 1 and readings of all the sensors are below safe concentration after time 33, which determine that the scheduling period with scheduling step 30 minutes of this contamination event is 16 hours. Scheduled by our agent, the contaminant concentration drops from 264.842 (reading of Sensor2) to 0.201 (reading of Sensor4). Table 3 has shown that hydrants are open in most situations that the readings of sensors are greater than the safe concentration threshold, which is consistent with common sense, because we always expect to discharge as much contaminants as possible, which indirectly shows that our method is feasible and effective.

    Table 3.  State within a scheduling period at the last episode of training process of CDQA. 0 or 1 means open or closed for a valve respectively, while 0 or 1 means closed or open for a hydrant respectively.
    TimeSensor1Sensor2Sensor3Sensor4Valve1Valve2Valve3Hydrant1Hydrant2Hydrant3
    10264.84200000000
    2064.09300001010
    3021.28300100110
    40197.59373.6430100110
    5057.5862.1130001111
    6099.784129.7513.506100110
    7013.6641.4882.045001100
    800190.99192.851100111
    90083.131131.996100111
    10002.71783.362001100
    1100090.745010101
    12027.993090.888010100
    13047.11069.01001101
    1407.576060.77000011
    15056.247053.248100001
    160.2514.56236.00513.280100111
    17022.85536.4927.804100111
    18019.99237.5521.577100111
    190038.8710100111
    2009.32118.86521.84100111
    21015.72225.55843.041100111
    22012.691.89622.235000100
    2305.26913.39827.858111101
    240010.0965.447110111
    250015.7224.598110111
    26005.6533.12110111
    270000.234110111
    280000.234110111
    290000.219110111
    300000.216110111
    310000.212110111
    320000.208110111
    330000.201110111

     | Show Table
    DownLoad: CSV

    In each episode of CDQA of training process, we use contamination scenes of a single source, but the experiment show that we can also get a desired result in multiple source scenes, which indicates that agent trained by CDQA algorithm have certain generalization for other contamination scenes without sampled in algorithm. In other words, we obtain a general agent which can solve the scheduling problem of uncertain contaminant event. Moreover, the trained agent receive the real time state and give a action instantly for scheduling of valves and hydrants, which saves lots of expensive computing time after contaminant event occurs.

    In this paper, we investigate the problem of valve and hydrant scheduling for contaminant water evacuation and water supply recovery in WDNs. We first give a comprehensive survey on existing solutions to this problem and notice that all previous studies need to precisely locate the contamination source before scheduling and then cost some time to search scheduling strategy. We therefore are motivated to propose a customized deep Q-learning based algorithm, with well design of the state, action and reward, to address this issue. This is the first time that deep reinforcement learning has been used to solve such problems as a real time scheduling problem. To evaluate the performance of our algorithm, we adopt EPANET to simulate various contaminant injection incidents in a typical WDN. The experiment results show that our algorithm can not only achieve good experimental results in single contamination source events, but also perform well in multiple contamination source events. Our work proves the feasibility and efficiency of applying deep reinforcement learning for valve and hydrant scheduling for contaminant water evacuation in WDNs.

    This research was partially supported by NSF of China (Grant No. 61673354) and National Key Research and Development Project(Grant No. 2016YFE0104400) and the State Key Lab of Digital Manufacturing Equipment and Technology, Huazhong University of Science and Technology (DMETKF2018020, DMETKF2019018). This paper has been subjected to Hubei Key Laboratory of Intelligent Geo-Information Processing, China University of Geosciences, Wuhan 430074, China.

    All authors declare no conflicts of interest in this paper.

    [1] Forster DH, Daschner FD (1998) Acinetobacter species as nosocomial pathogens. Eur J Clin Microbiol Infect Dis 17: 73–77. doi: 10.1007/BF01682159
    [2] Cisneros JM, Rodriguez-Bano J (2002) Nosocomial bacteremia due to Acinetobacter baumannii: epidemiology, clinical features and treatment. Clin Microbiol Infect 8: 687–693. doi: 10.1046/j.1469-0691.2002.00487.x
    [3] Bonomo RA, Szabo D (2006) Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin Infect Dis 43 Suppl 2: S49–56.
    [4] Devaud M, Kayser FH, Bächi B (1982) Transposon-mediated multiple antibiotic resistance in Acinetobacter strains. Antimicrob Agents Chemother 22: 323–329. doi: 10.1128/AAC.22.2.323
    [5] Chu YW, Leung CM, Houang ET, et al. (1999) Skin carriage of Acinetobacters in Hong Kong. J Clin Microbiol 37: 2962–2967.
    [6] Jawad A, Snelling AM, Heritage J, et al. (1998) Exceptional desiccation tolerance of Acinetobacter radioresistens. J Hosp Infect 39: 235–240. doi: 10.1016/S0195-6701(98)90263-8
    [7] Dijkshoorn L, Nemec A, Seifert H (2007) An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol 5: 939–951. doi: 10.1038/nrmicro1789
    [8] Lopes JM, Goulart EM, Starling CE (2007) Pediatric mortality due to nosocomial infection: a critical approach. Braz J Infect Dis 11: 515–519.
    [9] Kurcik-Trajkovska B (2009) Acinetobacter spp. - A serious enemy threatening hospitals worldwide. Maced J Med Sci 2: 157–162.
    [10] La Scola B, Fournier PE, Brouqui P, et al. (2001) Detection and culture of Bartonella quintana, Serratia marcescens, and Acinetobacter spp. from decontaminated human body lice. J Clin Microbiol 39: 1707–1709.
    [11] Tomaras AP, Dorsey CW, Edelmann RE, et al. (2003) Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology 149: 3473–3484. doi: 10.1099/mic.0.26541-0
    [12] Lee JC, Koerten H, van den Broek P, et al. (2006) Adherence of Acinetobacter baumannii strains to human bronchial epithelial cells. Res Microbiol 157: 360–366. doi: 10.1016/j.resmic.2005.09.011
    [13] Gospodarek E, Grzanka A, Dudziak Z, et al. (1998) Electron-microscopic observation of adherence of Acinetobacter baumannii to red blood cells. Acta Microbiol Pol 47: 213–217.
    [14] Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284: 1318–1322. doi: 10.1126/science.284.5418.1318
    [15] Rao RS, Karthika RU, Singh SP, et al. (2008) Correlation between biofilm production and multiple drug resistance in imipenem resistant clinical isolates of Acinetobacter baumannii. Indian J Med Microbiol 26: 333–337. doi: 10.4103/0255-0857.43566
    [16] Carpentier B, Cerf O (1993) Biofilms and their consequences, with particular reference to hygiene in the food industry. J Appl Bacteriol 75: 499–511. doi: 10.1111/j.1365-2672.1993.tb01587.x
    [17] Gilbert P, Brown MR (1998) Biofilms and beta-lactam activity. J Antimicrob Chemother 41: 571–572. doi: 10.1093/jac/41.5.571
    [18] Hausner M, Wuertz S (1999) High rates of conjugation in bacterial biofilms as determined by quantitative in situ analysis. Appl Environ Microbiol 65: 3710–3713.
    [19] Otto M (2009) Staphylococcus epidermidis--the 'accidental' pathogen. Nat Rev Microbiol 7: 555–567. doi: 10.1038/nrmicro2182
    [20] Peleg AY, Seifert H, Paterson DL (2008) Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 21: 538–582. doi: 10.1128/CMR.00058-07
    [21] Choi CH, Lee EY, Lee YC, et al. (2005) Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells. Cell Microbiol 7: 1127–1138. doi: 10.1111/j.1462-5822.2005.00538.x
    [22] Loehfelm TW, Luke NR, Campagnari AA (2008) Identification and characterization of an Acinetobacter baumannii biofilm-associated protein. J Bacteriol 190: 1036–1044. doi: 10.1128/JB.01416-07
    [23] Choi AH, Slamti L, Avci FY, et al. (2009) The pgaABCD locus of Acinetobacter baumannii encodes the production of poly-beta-1-6-N-acetylglucosamine, which is critical for biofilm formation. J Bacteriol 191: 5953–5963. doi: 10.1128/JB.00647-09
    [24] Gaddy JA, Tomaras AP, Actis LA (2009) The Acinetobacter baumannii 19606 OmpA protein plays a role in biofilm formation on abiotic surfaces and in the interaction of this pathogen with eukaryotic cells. Infect Immun 77: 3150–3160. doi: 10.1128/IAI.00096-09
    [25] Kim SW, Choi CH, Moon DC, et al. (2009) Serum resistance of Acinetobacter baumannii through the binding of factor H to outer membrane proteins. FEMS Microbiol Lett 301: 224–231. doi: 10.1111/j.1574-6968.2009.01820.x
    [26] Cabral MP, Soares NC, Aranda J, et al. (2011) Proteomic and functional analyses reveal a unique lifestyle for Acinetobacter baumannii biofilms and a key role for histidine metabolism. J Proteome Res 10: 3399–3417. doi: 10.1021/pr101299j
    [27] Choi CH, Lee JS, Lee YC, et al. (2008) Acinetobacter baumannii invades epithelial cells and outer membrane protein A mediates interactions with epithelial cells. BMC Microbiol 8: 216. doi: 10.1186/1471-2180-8-216
    [28] Clemmer KM, Bonomo RA, Rather PN (2011) Genetic analysis of surface motility in Acinetobacter baumannii. Microbiology 157: 2534–2544. doi: 10.1099/mic.0.049791-0
    [29] Itoh Y, Rice JD, Goller C, et al. (2008) Roles of pgaABCD genes in synthesis, modification, and export of the Escherichia coli biofilm adhesin poly-beta-1,6-N-acetyl-D-glucosamine. J Bacteriol 190: 3670–3680. doi: 10.1128/JB.01920-07
    [30] Cramton SE, Gerke C, Schnell NF, et al. (1999) The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect Immun 67: 5427–5433.
    [31] Kropec A, Maira-Litran T, Jefferson KK, et al. (2005) Poly-N-acetylglucosamine production in Staphylococcus aureus is essential for virulence in murine models of systemic infection. Infect Immun 73: 6868–6876. doi: 10.1128/IAI.73.10.6868-6876.2005
    [32] Lewis K (2001) Riddle of biofilm resistance. Antimicrob Agents Chemother 45: 999–1007. doi: 10.1128/AAC.45.4.999-1007.2001
    [33] Tomaras AP, Flagler MJ, Dorsey CW, et al. (2008) Characterization of a two-component regulatory system from Acinetobacter baumannii that controls biofilm formation and cellular morphology. Microbiology 154: 3398–3409. doi: 10.1099/mic.0.2008/019471-0
    [34] Luo LM, Wu LJ, Xiao YL, et al. (2015) Enhancing pili assembly and biofilm formation in Acinetobacter baumannii ATCC19606 using non-native acyl-homoserine lactones. BMC Microbiol 15: 62. doi: 10.1186/s12866-015-0397-5
    [35] Mussi MA, Limansky AS, Viale AM (2005) Acquisition of resistance to carbapenems in multidrug-resistant clinical strains of Acinetobacter baumannii: natural insertional inactivation of a gene encoding a member of a novel family of beta-barrel outer membrane proteins. Antimicrob Agents Chemother 49: 1432–1440. doi: 10.1128/AAC.49.4.1432-1440.2005
    [36] Poirel L, Lebessi E, Héritier C, et al. (2006) Nosocomial spread of OXA-58-positive carbapenem-resistant Acinetobacter baumannii isolates in a paediatric hospital in Greece. Clin Microbiol Infect 12: 1138–1141. doi: 10.1111/j.1469-0691.2006.01537.x
    [37] Aranda J, Bardina C, Beceiro A, et al. (2011) Acinetobacter baumannii RecA protein in repair of DNA damage, antimicrobial resistance, general stress response, and virulence. J Bacteriol 193: 3740–3747. doi: 10.1128/JB.00389-11
    [38] Diggle SP, Crusz SA, Camara M (2007) Quorum sensing. Curr Biol 17: R907–910. doi: 10.1016/j.cub.2007.08.045
    [39] Uroz S, Dessaux Y, Oger P (2009) Quorum sensing and quorum quenching: the yin and yang of bacterial communication. Chembiochem 10: 205–216. doi: 10.1002/cbic.200800521
    [40] Whitehead NA, Barnard AM, Slater H, et al. (2001) Quorum-sensing in Gram-negative bacteria. FEMS Microbiol Rev 25: 365–404. doi: 10.1111/j.1574-6976.2001.tb00583.x
    [41] Holden I, Swift I, Williams I (2000) New signal molecules on the quorum-sensing block. Trends Microbiol 8: 101–104; discussion 103–104. doi: 10.1016/S0966-842X(00)01718-2
    [42] Irie Y, Parsek MR (2008) Quorum sensing and microbial biofilms. Curr Top Microbiol Immunol 322: 67–84.
    [43] Williams P (2006) Quorum sensing. Int J Med Microbiol 296: 57–59. doi: 10.1016/j.ijmm.2006.01.034
    [44] Schaefer AL, Hanzelka BL, Eberhard A, et al. (1996) Quorum sensing in Vibrio fischeri: probing autoinducer-LuxR interactions with autoinducer analogs. J Bacteriol 178: 2897–2901.
    [45] González RH, Nusblat A, Nudel BC (2001) Detection and characterization of quorum sensing signal molecules in Acinetobacter strains. Microbiol Res 155: 271–277. doi: 10.1016/S0944-5013(01)80004-5
    [46] González RH, Dijkshoorn L, Van den Barselaar M, et al. (2009) Quorum sensing signal profile of Acinetobacter strains from nosocomial and environmental sources. Rev Argent Microbiol 41: 73–78.
    [47] Prashanth K, Vasanth T, Saranathan R, et al. (2012) Antibiotic resistance, biofilms and quorum 487 sensing in Acinetobacter species, In: Antibiotic resistant bacteria - A coninuous challenge in the 488 new millennium, Dr. Marina Pana (Ed.); Croatia : InTech, 179–212.
    [48] Niu C, Clemmer KM, Bonomo RA, et al. (2008) Isolation and characterization of an autoinducer synthase from Acinetobacter baumannii. J Bacteriol 190: 3386–3392. doi: 10.1128/JB.01929-07
    [49] Stevens AM, Dolan KM, Greenberg EP (1994) Synergistic binding of the Vibrio fischeri LuxR transcriptional activator domain and RNA polymerase to the lux promoter region. Proc Natl Acad Sci U S A 91: 12619–12623. doi: 10.1073/pnas.91.26.12619
    [50] Egland KA, Greenberg EP (2001) Quorum sensing in Vibrio fischeri: analysis of the LuxR DNA binding region by alanine-scanning mutagenesis. J Bacteriol 183: 382–386. doi: 10.1128/JB.183.1.382-386.2001
    [51] Latifi A, Winson MK, Foglino M, et al. (1995) Multiple homologues of LuxR and LuxI control expression of virulence determinants and secondary metabolites through quorum sensing in Pseudomonas aeruginosa PAO1. Mol Microbiol 17: 333–343. doi: 10.1111/j.1365-2958.1995.mmi_17020333.x
    [52] Gray KM, Garey JR (2001) The evolution of bacterial LuxI and LuxR quorum sensing regulators. Microbiology 147: 2379–2387. doi: 10.1099/00221287-147-8-2379
    [53] Bhargava N, Sharma P, Capalash N (2010) Quorum sensing in Acinetobacter: an emerging pathogen. Crit Rev Microbiol 36: 349-360. doi: 10.3109/1040841X.2010.512269
    [54] Surette MG, Miller MB, Bassler BL (1999) Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: a new family of genes responsible for autoinducer production. Proc Natl Acad Sci U S A 96: 1639–1644. doi: 10.1073/pnas.96.4.1639
    [55] Young DM, Parke D, Ornston LN (2005) Opportunities for genetic investigation afforded by Acinetobacter baylyi, a nutritionally versatile bacterial species that is highly competent for natural transformation. Annu Rev Microbiol 59: 519–551. doi: 10.1146/annurev.micro.59.051905.105823
    [56] Smith MG, Gianoulis TA, Pukatzki S, et al. (2007) New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis. Genes Dev 21: 601–614. doi: 10.1101/gad.1510307
    [57] Oh MH, Choi CH (2015) Role of LuxIR homologue AnoIR in Acinetobacter nosocomialis and the effect of virstatin on the expression of anoR Gene. J Microbiol Biotechnol 25: 1390–1400. doi: 10.4014/jmb.1504.04069
    [58] Taccone FS, Rodriguez-Villalobos H, De Backer D, et al. (2006) Successful treatment of septic shock due to pan-resistant Acinetobacter baumannii using combined antimicrobial therapy including tigecycline. Eur J Clin Microbiol Infect Dis 25: 257–260. doi: 10.1007/s10096-006-0123-1
    [59] Valencia R, Arroyo LA, Conde M, et al. (2009) Nosocomial outbreak of infection with pan-drug-resistant Acinetobacter baumannii in a tertiary care university hospital. Infect Control Hosp Epidemiol 30: 257–263. doi: 10.1086/595977
    [60] Amaral L, Martins A, Spengler G, et al. (2014) Efflux pumps of Gram-negative bacteria: what they do, how they do it, with what and how to deal with them. Front Pharmacol 4: 168.
    [61] Balaban N, Cirioni O, Giacometti A, et al. (2007) Treatment of Staphylococcus aureus biofilm infection by the quorum-sensing inhibitor RIP. Antimicrob Agents Chemother 51: 2226–2229. doi: 10.1128/AAC.01097-06
    [62] Hoffman LR, D'Argenio DA, MacCoss MJ, et al. (2005) Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 436: 1171–1175. doi: 10.1038/nature03912
    [63] Henikoff S, Wallace JC, Brown JP (1990) Finding protein similarities with nucleotide sequence databases. Methods Enzymol 183: 111–132. doi: 10.1016/0076-6879(90)83009-X
    [64] Rahmati S, Yang S, Davidson AL, et al. (2002) Control of the AcrAB multidrug efflux pump by quorum-sensing regulator SdiA. Mol Microbiol 43: 677–685. doi: 10.1046/j.1365-2958.2002.02773.x
    [65] Maseda H, Sawada I, Saito K, et al. (2004) Enhancement of the mexAB-oprM efflux pump expression by a quorum-sensing autoinducer and its cancellation by a regulator, MexT, of the mexEF-oprN efflux pump operon in Pseudomonas aeruginosa. Antimicrob Agents Chemother 48: 1320–1328. doi: 10.1128/AAC.48.4.1320-1328.2004
    [66] Chu YW, Chau SL, Houang ET (2006) Presence of active efflux systems AdeABC, AdeDE and AdeXYZ in different Acinetobacter genomic DNA groups. J Med Microbiol 55: 477–478. doi: 10.1099/jmm.0.46433-0
    [67] Nemec A, Maixnerova M, van der Reijden TJ, et al. (2007) Relationship between the AdeABC efflux system gene content, netilmicin susceptibility and multidrug resistance in a genotypically diverse collection of Acinetobacter baumannii strains. J Antimicrob Chemother 60: 483–489. doi: 10.1093/jac/dkm231
    [68] Yoon EJ, Courvalin P, Grillot-Courvalin C (2013) RND-type efflux pumps in multidrug-resistant clinical isolates of Acinetobacter baumannii: major role for AdeABC overexpression and AdeRS mutations. Antimicrob Agents Chemother 57: 2989–2995. doi: 10.1128/AAC.02556-12
    [69] Coyne S, Courvalin P, Périchon B (2011) Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 55: 947–953. doi: 10.1128/AAC.01388-10
    [70] He X, Lu F, Yuan F, et al. (2015) Biofilm formation caused by clinical Acinetobacter baumannii isolates is associated with overexpression of the AdeFGH Efflux pump. Antimicrob Agents Chemother 59: 4817–4825. doi: 10.1128/AAC.00877-15
    [71] Kayama S, Murakami K, Ono T, et al. (2009) The role of rpoS gene and quorum-sensing system in ofloxacin tolerance in Pseudomonas aeruginosa. FEMS Microbiol Lett 298: 184–192. doi: 10.1111/j.1574-6968.2009.01717.x
    [72] Que YA, Hazan R, Strobel B, et al. (2013) A quorum sensing small volatile molecule promotes antibiotic tolerance in bacteria. PLoS One 8: e80140. doi: 10.1371/journal.pone.0080140
    [73] Khan MS, Zahin M, Hasan S, et al. (2009) Inhibition of quorum sensing regulated bacterial functions by plant essential oils with special reference to clove oil. Lett Appl Microbiol 49: 354–360. doi: 10.1111/j.1472-765X.2009.02666.x
    [74] Sperandio V (2007) Novel approaches to bacterial infection therapy by interfering with bacteria-to-bacteria signaling. Expert Rev Anti Infect Ther 5: 271–276. doi: 10.1586/14787210.5.2.271
    [75] Stacy DM, Welsh MA, Rather PN, et al. (2012) Attenuation of quorum sensing in the pathogen Acinetobacter baumannii using non-native N-Acyl homoserine lactones. ACS Chem Biol 7: 1719–1728. doi: 10.1021/cb300351x
    [76] Saroj SD, Rather PN (2013) Streptomycin inhibits quorum sensing in Acinetobacter baumannii. Antimicrob Agents Chemother 57: 1926–1929. doi: 10.1128/AAC.02161-12
    [77] Chabane YN, Mlouka MB, Alexandre S, et al. (2014) Virstatin inhibits biofilm formation and motility of Acinetobacter baumannii. BMC Microbiol 14: 62. doi: 10.1186/1471-2180-14-62
    [78] Choo JH, Rukayadi Y, Hwang JK (2006) Inhibition of bacterial quorum sensing by vanilla extract. Lett Appl Microbiol 42: 637–641.
    [79] Rasmussen TB, Bjarnsholt T, Skindersoe ME, et al. (2005) Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J Bacteriol 187: 1799–1814. doi: 10.1128/JB.187.5.1799-1814.2005
    [80] Cady NC, McKean KA, Behnke J, et al. (2012) Inhibition of biofilm formation, quorum sensing and infection in Pseudomonas aeruginosa by natural products-inspired organosulfur compounds. PLoS One 7: e38492. doi: 10.1371/journal.pone.0038492
    [81] Sambanthamoorthy K, Luo C, Pattabiraman N, et al. (2014) Identification of small molecules inhibiting diguanylate cyclases to control bacterial biofilm development. Biofouling 30: 17–28. doi: 10.1080/08927014.2013.832224
    [82] Dong YH, Wang LH, Xu JL, et al. (2001) Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase. Nature 411: 813–817. doi: 10.1038/35081101
    [83] Chow JY, Yang Y, Tay SB, et al. (2014) Disruption of biofilm formation by the human pathogen Acinetobacter baumannii using engineered quorum-quenching lactonases. Antimicrob Agents Chemother 58: 1802–1805. doi: 10.1128/AAC.02410-13
    [84] Hoang TT, Schweizer HP (1999) Characterization of Pseudomonas aeruginosa enoyl-acyl carrier protein reductase (FabI): a target for the antimicrobial triclosan and its role in acylated homoserine lactone synthesis. J Bacteriol 181: 5489–5497.
    [85] Jarrett CO, Deak E, Isherwood KE, et al. (2004) Transmission of Yersinia pestis from an infectious biofilm in the flea vector. J Infect Dis 190: 783–792. doi: 10.1086/422695
    [86] Czajkowski R, Jafra S (2009) Quenching of acyl-homoserine lactone-dependent quorum sensing by enzymatic disruption of signal molecules. Acta Biochim Pol 56: 1–16.
    [87] Lin YH, Xu JL, Hu J, et al. (2003) Acyl-homoserine lactone acylase from Ralstonia strain XJ12B represents a novel and potent class of quorum-quenching enzymes. Mol Microbiol 47: 849–860. doi: 10.1046/j.1365-2958.2003.03351.x
    [88] Romero M, Diggle SP, Heeb S, et al. (2008) Quorum quenching activity in Anabaena sp. PCC 7120: identification of AiiC, a novel AHL-acylase. FEMS Microbiol Lett 280: 73–80.
    [89] Uroz S, Oger PM, Chapelle E, et al. (2008) A Rhodococcus qsdA-encoded enzyme defines a novel class of large-spectrum quorum-quenching lactonases. Appl Environ Microbiol 74: 1357–1366. doi: 10.1128/AEM.02014-07
    [90] Chow JY, Xue B, Lee KH, et al. (2010) Directed evolution of a thermostable quorum-quenching lactonase from the amidohydrolase superfamily. J Biol Chem 285: 40911–40920. doi: 10.1074/jbc.M110.177139
    [91] Kiran S (2011) Enzymatic quorum quenching increases antibiotic susceptibility of multidrug resistant Pseudomonas aeruginosa. Irani J Microbiol 3: 1–12.
    [92] Limsuwan S, Subhadhirasakul S, Voravuthikunchai PS (2009) Medicinal plants with significant activity against important pathogenic bacteria. Pharm Biol 47: 683–689. doi: 10.1080/13880200902930415
    [93] Babić F, Venturi V, Maravić-Vlahoviček G (2010) Tobramycin at subinhibitory concentration inhibits the RhlI/R quorum sensing system in a Pseudomonas aeruginosa environmental isolate. BMC Infect Dis 10: 148. doi: 10.1186/1471-2334-10-148
    [94] Defoirdt T, Boon N, Bossier P (2010) Can bacteria evolve resistance to quorum sensing disruption? PLoS Pathog 6: e1000989. doi: 10.1371/journal.ppat.1000989
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    9. Xingwang Shen, Shimin Liu, Bin Zhou, Tao Wu, Qi Zhang, Jinsong Bao, Digital Twin-Driven Reinforcement Learning Method for Marine Equipment Vehicles Scheduling Problem, 2024, 21, 1545-5955, 2173, 10.1109/TASE.2023.3289915
    10. Xingwang Shen, Shimin Liu, Bin Zhou, Yu Zheng, Jinsong Bao, 2022, Digital twin-based scheduling method for marine equipment material transportation vehicles, 978-1-6654-9042-9, 100, 10.1109/CASE49997.2022.9926428
    11. Roberto Ortega, Dana Carciumaru, Alexandra D. Cazares-Moreno, Reinforcement learning for watershed and aquifer management: a nationwide view in the country of Mexico with emphasis in Baja California Sur, 2024, 6, 2624-9375, 10.3389/frwa.2024.1384595
    12. Tymoteusz Miller, Grzegorz Michoński, Irmina Durlik, Polina Kozlovska, Paweł Biczak, Artificial Intelligence in Aquatic Biodiversity Research: A PRISMA-Based Systematic Review, 2025, 14, 2079-7737, 520, 10.3390/biology14050520
    13. Yu Zheng, Qianyue Hao, Jingwei Wang, Changzheng Gao, Jinwei Chen, Depeng Jin, Yong Li, A Survey of Machine Learning for Urban Decision Making: Applications in Planning, Transportation, and Healthcare, 2025, 57, 0360-0300, 1, 10.1145/3695986
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