Review

An overview of the antimicrobial resistance mechanisms of bacteria

  • Received: 18 April 2018 Accepted: 13 June 2018 Published: 26 June 2018
  • Resistance to antimicrobial agents has become a major source of morbidity and mortality worldwide. When antibiotics were first introduced in the 1900’s, it was thought that we had won the war against microorganisms. It was soon discovered however, that the microorganisms were capable of developing resistance to any of the drugs that were used. Apparently most pathogenic microorganisms have the capability of developing resistance to at least some antimicrobial agents. The main mechanisms of resistance are: limiting uptake of a drug, modification of a drug target, inactivation of a drug, and active efflux of a drug. These mechanisms may be native to the microorganisms, or acquired from other microorganisms. Understanding more about these mechanisms should hopefully lead to better treatment options for infective diseases, and development of antimicrobial drugs that can withstand the microorganisms attempts to become resistant.

    Citation: Wanda C Reygaert. An overview of the antimicrobial resistance mechanisms of bacteria[J]. AIMS Microbiology, 2018, 4(3): 482-501. doi: 10.3934/microbiol.2018.3.482

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  • Resistance to antimicrobial agents has become a major source of morbidity and mortality worldwide. When antibiotics were first introduced in the 1900’s, it was thought that we had won the war against microorganisms. It was soon discovered however, that the microorganisms were capable of developing resistance to any of the drugs that were used. Apparently most pathogenic microorganisms have the capability of developing resistance to at least some antimicrobial agents. The main mechanisms of resistance are: limiting uptake of a drug, modification of a drug target, inactivation of a drug, and active efflux of a drug. These mechanisms may be native to the microorganisms, or acquired from other microorganisms. Understanding more about these mechanisms should hopefully lead to better treatment options for infective diseases, and development of antimicrobial drugs that can withstand the microorganisms attempts to become resistant.


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    [1] World Health Organization (2014) World Health Statistics 2014.
    [2] World Health Organization (2015) Global action plan on antimicrobial resistance.
    [3] Griffith M, Postelnick M, Scheetz M (2012) Antimicrobial stewardship programs: methods of operation and suggested outcomes. Expert Rev Anti-Infe 10: 63–73. doi: 10.1586/eri.11.153
    [4] Yu VL (2011) Guidelines for hospital-acquired pneumonia and health-care-associated pneumonia: a vulnerability, a pitfall, and a fatal flaw. Lancet Infect Dis 11: 248–252. doi: 10.1016/S1473-3099(11)70005-6
    [5] Goossens H (2009) Antibiotic consumption and link to resistance. Clin Microbiol Infec 15 3:12–15.
    [6] Pakyz AL, MacDougall C, Oinonen M, et al. (2008) Trends in antibacterial use in US academic health centers: 2002 to 2006. Arch Intern Med 168: 2254–2260. doi: 10.1001/archinte.168.20.2254
    [7] Tacconelli E (2009) Antimicrobial use: risk driver of multidrug resistant microorganisms in healthcare settings. Curr Opin Infect Dis 22: 352–358. doi: 10.1097/QCO.0b013e32832d52e0
    [8] Landers TF, Cohen B, Wittum TE, et al. (2012) A review of antibiotic use in food animals: perspective, policy, and potential. Public Health Rep 127: 4–22. doi: 10.1177/003335491212700103
    [9] Wegener HC (2012) Antibiotic resistance-Linking human and animal health, In: Improving food safety through a One Health approach, Washington: National Academy of Sciences, 331–349.
    [10] Centers for Disease Control and Prevention (CDC) (2013) Antibiotic resistance threats in the United States, 2013, U.S, Department of Health and Human Services, CS239559-B.
    [11] Maragakis LL, Perencevich EN, Cosgrove SE (2008) Clinical and economic burden of antimicrobial resistance. Expert Rev Anti-Infe 6: 751–763. doi: 10.1586/14787210.6.5.751
    [12] Filice GA, Nyman JA, Lexau C, et al. (2010) Excess costs and utilization associated with methicillin resistance for patients with Staphylococcus aureus infection. Infect Cont Hosp Ep 31: 365–373. doi: 10.1086/651094
    [13] Hübner C, Hübner NO, Hopert K, et al. (2014) Analysis of MRSA-attributed costs of hospitalized patients in Germany. Eur J Clin Microbiol 33: 1817–1822. doi: 10.1007/s10096-014-2131-x
    [14] Macedo-Viñas M, De Angelis G, Rohner P, et al. (2013) Burden of methicillin-resistant Staphylococcus aureus infections at a Swiss University hospital: excess length of stay and costs. J Hosp Infect 84: 132–137. doi: 10.1016/j.jhin.2013.02.015
    [15] Pakyz A, Powell JP, Harpe SE, et al. (2008) Diversity of antimicrobial use and resistance in 42 hospitals in the United States. Pharmacotherapy 28: 906–912. doi: 10.1592/phco.28.7.906
    [16] Sandiumenge A, Diaz E, Rodriguez A, et al. (2006) Impact of diversity of antibiotic use on the development of antimicrobial resistance. J Antimicrob Chemoth 57: 1197–1204. doi: 10.1093/jac/dkl097
    [17] Wood TK, Knabel SJ, Kwan BW (2013) Bacterial persister cell formation and dormancy. Appl Environ Microbiol 79: 7116–7121. doi: 10.1128/AEM.02636-13
    [18] Keren I, Kaldalu N, Spoering A, et al. (2004) Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett 230: 13–18. doi: 10.1016/S0378-1097(03)00856-5
    [19] Coculescu BI (2009) Antimicrobial resistance induced by genetic changes. J Med Life 2: 114–123.
    [20] Martinez JL (2014) General principles of antibiotic resistance in bacteria. Drug Discov Today 11: 33–39. doi: 10.1016/j.ddtec.2014.02.001
    [21] Cox G, Wright GD (2013) Intrinsic antibiotic resistance: mechanisms, origins, challenges and solutions. Int J Med Microbiol 303: 287–292. doi: 10.1016/j.ijmm.2013.02.009
    [22] Fajardo A, Martinez-Martin N, Mercadillo M, et al. (2008) The neglected intrinsic resistome of bacterial pathogens. PLoS One 3: e1619. doi: 10.1371/journal.pone.0001619
    [23] Davies J, Davies D (2010) Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 74: 417–433. doi: 10.1128/MMBR.00016-10
    [24] Reygaert WC (2009) Methicillin-resistant Staphylococcus aureus (MRSA): molecular aspects of antimicrobial resistance and virulence. Clin Lab Sci 22: 115–119.
    [25] Blázquez J, Couce A, Rodríguez-Beltrán J, et al. (2012) Antimicrobials as promoters of genetic variation. Curr Opin Microbiol 15: 561–569. doi: 10.1016/j.mib.2012.07.007
    [26] Chancey ST, Zähner D, Stephens DS (2012) Acquired inducible antimicrobial resistance in Gram-positive bacteria. Future Microbiol 7: 959–978. doi: 10.2217/fmb.12.63
    [27] Mahon CR, Lehman DC, Manuselis G (2014) Antimicrobial agent mechanisms of action and resistance, In: Textbook of Diagnostic Microbiology, St. Louis: Saunders, 254–273.
    [28] Blair JM, Richmond GE, Piddock LJ (2014) Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. Future Microbiol 9: 1165–1177. doi: 10.2217/fmb.14.66
    [29] Kumar A, Schweizer HP (2005) Bacterial resistance to antibiotics: active efflux and reduced uptake. Adv Drug Deliver Rev 57: 1486–1513. doi: 10.1016/j.addr.2005.04.004
    [30] Lambert PA (2002) Cellular impermeability and uptake of biocides and antibiotics in gram-positive bacteria and mycobacteria. J Appl Microbiol 92: 46S–54S. doi: 10.1046/j.1365-2672.92.5s1.7.x
    [31] Bébéar CM, Pereyre S (2005) Mechanisms of drug resistance in Mycoplasma pneumoniae. Curr Drug Targets 5: 263–271. doi: 10.2174/1568005054880109
    [32] Miller WR, Munita JM, Arias CA (2014) Mechanisms of antibiotic resistance in enterococci. Expert Rev Anti-Infe 12: 1221–1236. doi: 10.1586/14787210.2014.956092
    [33] Gill MJ, Simjee S, Al-Hattawi K, et al. (1998) Gonococcal resistance to β-lactams and tetracycline involves mutation in loop 3 of the porin encoded at the penB locus. Antimicrob Agents Ch 42: 2799–2803.
    [34] Cornaglia G, Mazzariol A, Fontana R, et al. (1996) Diffusion of carbapenems through the outer membrane of enterobacteriaceae and correlation of their activities with their periplasmic concentrations. Microb Drug Resist 2: 273–276. doi: 10.1089/mdr.1996.2.273
    [35] Chow JW, Shlaes DM (1991) Imipenem resistance associated with the loss of a 40 kDa outer membrane protein in Enterobacter aerogenes. J Antimicrob Chemoth 28: 499–504. doi: 10.1093/jac/28.4.499
    [36] Thiolas A, Bornet C, Davin-Régli A, et al. (2004) Resistance to imipenem, cefepime, and cefpirome associated with mutation in Omp36 osmoporin of Enterobacter aerogenes. Biochem Bioph Res Co 317: 851–856. doi: 10.1016/j.bbrc.2004.03.130
    [37] Mah TF (2012) Biofilm-specific antibiotic resistance. Future Microbiol 7: 1061–1072. doi: 10.2217/fmb.12.76
    [38] Soto SM (2013) Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm. Virulence 4: 223–229. doi: 10.4161/viru.23724
    [39] Van Acker H, Van Dijck P, Coenye T (2014) Molecular mechanisms of antimicrobial tolerance and resistance in bacterial and fungal biofilms. Trends Microbiol 22: 326–333. doi: 10.1016/j.tim.2014.02.001
    [40] Beceiro A, Tomás M, Bou G (2013) Antimicrobial resistance and virulence: a successful or deleterious association in the bacterial world? Clin Microbiol Rev 26: 185–230. doi: 10.1128/CMR.00059-12
    [41] Randall CP, Mariner KR, Chopra I, et al. (2013) The target of daptomycin is absent form Escherichia coli and other gram-negative pathogens. Antimicrob Agents Ch 57: 637–639. doi: 10.1128/AAC.02005-12
    [42] Yang SJ, Kreiswirth BN, Sakoulas G, et al. (2009) Enhanced expression of dltABCD is associated with development of daptomycin nonsusceptibility in a clinical endocarditis isolate of Staphylococcus aureus. J Infect Dis 200: 1916–1920. doi: 10.1086/648473
    [43] Mishra NN, Bayer AS, Weidenmaier C, et al. (2014) Phenotypic and genotypic characterization of daptomycin-resistant methicillin-resistant Staphylococcus aureus strains: relative roles of mprF and dlt operons. PLoS One 9: e107426. doi: 10.1371/journal.pone.0107426
    [44] Stefani S, Campanile F, Santagati M, et al. (2015) Insights and clinical perspectives of daptomycin resistance in Staphylococcus aureus: a review of the available evidence. Int J Antimicrob Agents 46: 278–289. doi: 10.1016/j.ijantimicag.2015.05.008
    [45] Kumar S, Mukherjee MM, Varela MF (2013) Modulation of bacterial multidrug resistance efflux pumps of the major facilitator superfamily. Int J Bacteriol.
    [46] Roberts MC (2003) Tetracycline therapy: update. Clin Infect Dis 36: 462–467. doi: 10.1086/367622
    [47] Roberts MC (2004) Resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics. Mol Biotechnol 28: 47–62. doi: 10.1385/MB:28:1:47
    [48] Hawkey PM (2003) Mechanisms of quinolone action and microbial response. J Antimicrob Chemoth 1: 28–35.
    [49] Redgrave LS, Sutton SB, Webber MA, et al. (2014) Fluoroquinolone resistance: mechanisms, impact on bacteria, and role in evolutionary success. Trends Microbiol 22: 438–445. doi: 10.1016/j.tim.2014.04.007
    [50] Huovinen P, Sundström L, Swedberg G, et al. (1995) Trimethoprim and sulfonamide resistance. Antimicrob Agents Ch 39: 279–289. doi: 10.1128/AAC.39.2.279
    [51] Vedantam G, Guay GG, Austria NE, et al. (1998) Characterization of mutations contributing to sulfathiazole resistance in Escherichia coli. Antimicrob Agents Ch 42: 88–93.
    [52] Blair JM, Webber MA, Baylay AJ, et al. (2015) Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol 13: 42–51. doi: 10.1038/nrmicro3380
    [53] Ramirez MS, Tolmasky ME (2010) Aminoglycoside modifying enzymes. Drug Resist Update 13: 151–171. doi: 10.1016/j.drup.2010.08.003
    [54] Robicsek A, Strahilevitz J, Jacoby GA, et al. (2006) Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nat Med 12: 83–88. doi: 10.1038/nm1347
    [55] Schwarz S, Kehrenberg C, Doublet B, et al. (2004) Molecular basis of bacterial resistance to chloramphenicol and florfenicol. FEMS Microbiol Rev 28: 519–542. doi: 10.1016/j.femsre.2004.04.001
    [56] Pfeifer Y, Cullik A, Witte W (2010) Resistance to cephalosporins and carbapenems in Gram-negative bacterial pathogens. Int J Med Microbiol 300: 371–379. doi: 10.1016/j.ijmm.2010.04.005
    [57] Bush K, Bradford PA (2016) β-Lactams and β-lactamase inhibitors: an overview. CSH Perspect Med 6: a02527.
    [58] Bush K, Jacoby GA (2010) Updated functional classification of β-lactamases. Antimicrob Agents Ch 54: 969–976. doi: 10.1128/AAC.01009-09
    [59] Schultsz C, Geerlings S (2012) Plasmid-mediated resistance in Enterobacteriaceae. Drugs 72: 1–16.
    [60] Bush K (2013) Proliferation and significance of clinically relevant β-lactamases. Ann NY Acad Sci 1277: 84–90. doi: 10.1111/nyas.12023
    [61] Reygaert WC (2013) Antimicrobial resistance mechanisms of Staphylococcus aureus, In: Microbial pathogens and strategies for combating them: science, technology and education, Spain: Formatex, 297–310.
    [62] Toth M, Antunes NT, Stewart NK, et al. (2016) Class D β-lactamases do exist in Gram-positive bacteria. Nat Chem Biol 12: 9–14. doi: 10.1038/nchembio.1950
    [63] Jacoby GA (2009) AmpC β-lactamases. Clin Microbiol Rev 22: 161–182. doi: 10.1128/CMR.00036-08
    [64] Thomson KS (2010) Extended-spectrum-β-lactamase, AmpC, and carbapenemase issues. J Clin Microbiol 48: 1019–1025. doi: 10.1128/JCM.00219-10
    [65] Lahlaoui H, Khalifa ABH, Mousa MB (2014) Epidemiology of Enterobacteriaceae producing CTX-M type extended spectrum β-lactamase (ESBL). Med Maladies Infect 44: 400–404. doi: 10.1016/j.medmal.2014.03.010
    [66] Bevan ER, Jones AM, Hawkey PM (2017) Global epidemiology of CTX-M β-lactamases: temporal and geographical shifts in genotype. J Antimicrob Chemoth 72: 2145–2155. doi: 10.1093/jac/dkx146
    [67] Bajaj P, Singh NS, Virdi JS (2016) Escherichia coli β-lactamases: what really matters. Front Microbiol 7: 417.
    [68] Friedman ND, Tomkin E, Carmeli Y (2016) The negative impact of antibiotic resistance. Clin Microbiol Infect 22: 416–422. doi: 10.1016/j.cmi.2015.12.002
    [69] Zhanel GG, Lawson CD, Adam H, et al. (2013) Ceftazidime-Avibactam: a novel cephalosporin/β-lactamase inhibitor combination. Drugs 73: 159–177. doi: 10.1007/s40265-013-0013-7
    [70] Bush K (2018) Game changers: new β-lactamase inhibitor combinations targeting antibiotic resistance in gram-negative bacteria. ACS Infect Dis 4: 84–87. doi: 10.1021/acsinfecdis.7b00243
    [71] Docquier JD, Mangani S (2018) An update on β-lactamase inhibitor discovery and development. Drug Resist Update 36: 13–29. doi: 10.1016/j.drup.2017.11.002
    [72] Villagra NA, Fuentes JA, Jofré MR, et al. (2012) The carbon source influences the efflux pump-mediated antimicrobial resistance in clinically important Gram-negative bacteria. J Antimicrob Chemoth 67: 921–927. doi: 10.1093/jac/dkr573
    [73] Piddock LJ (2006) Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev 19: 382–402. doi: 10.1128/CMR.19.2.382-402.2006
    [74] Poole K (2007) Efflux pumps as antimicrobial resistance mechanisms. Ann Med 39: 162–176. doi: 10.1080/07853890701195262
    [75] Tanabe M, Szakonyi G, Brown KA, et al. (2009) The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a dimer in vitro. Biochem Bioph Res Co 380: 338–342. doi: 10.1016/j.bbrc.2009.01.081
    [76] Jo I, Hong S, Lee M, et al. (2017) Stoichiometry and mechanistic implications of the MacAB-TolC tripartite efflux pump. Biochem Bioph Res Co 494: 668–673. doi: 10.1016/j.bbrc.2017.10.102
    [77] Jonas BM, Murray BE, Weinstock GM (2001) Characterization of emeA, a norA homolog and multidrug resistance efflux pump, in Enterococcus faecalis. Antimicrob Agents Ch 45: 3574–3579. doi: 10.1128/AAC.45.12.3574-3579.2001
    [78] Truong-Bolduc QC, Dunman PM, Strahilevitz J, et al. (2005) MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J Bacteriol 187: 2395–2405. doi: 10.1128/JB.187.7.2395-2405.2005
    [79] Kourtesi C, Ball AR, Huang YY, et al. (2013) Microbial efflux systems and inhibitors: approaches to drug discovery and the challenge of clinical implementation. Open Microbiol J 7: 34–52. doi: 10.2174/1874285801307010034
    [80] Costa SS, Viveiros M, Amaral L, et al. (2013) Multidrug efflux pumps in Staphylococcus aureus: an update. Open Microbiol J 7: 59–71. doi: 10.2174/1874285801307010059
    [81] Lubelski J, Konings WN, Driessen AJ (2007) Distribution and physiology of ABC-type transporters contributing to multidrug resistance in bacteria. Microbiol Mol Biol Rev 71: 463–476. doi: 10.1128/MMBR.00001-07
    [82] Putman M, van Veen HW, Konings WN (2000) Molecular properties of bacterial multidrug transporters. Microbiol Mol Biol Rev 64: 672–693. doi: 10.1128/MMBR.64.4.672-693.2000
    [83] Kuroda T, Tsuchiya T (2009) Multidrug efflux transporters in the MATE family. BBA-Proteins Proteom 1794: 763–768. doi: 10.1016/j.bbapap.2008.11.012
    [84] Rouquette-Loughlin, C, Dunham SA, Kuhn M, et al. (2003) The NorM efflux pump of Neisseria gonorrhoeae and Neisseria meningitidis recognizes antimicrobial cationic compounds. J Bacteriol 185: 1101–1106. doi: 10.1128/JB.185.3.1101-1106.2003
    [85] Bay DC, Rommens KL, Turner RJ (2008) Small multidrug resistance proteins: a multidrug transporter family that continues to grow. BBA-Biomembranes 1778: 1814–1838. doi: 10.1016/j.bbamem.2007.08.015
    [86] Yerushalmi H, Lebendiker M, Schuldiner S (1995) EmrE, an Escherichia coli 12-kDa multidrug transporter, exchanges toxic cations and H+ and is soluble in organic solvents. J Biol Chem 270: 6856–6863. doi: 10.1074/jbc.270.12.6856
    [87] Collu F, Cascella M (2013) Multidrug resistance and efflux pumps: insights from molecular dynamics simulations. Curr Top Med Chem 13: 3165–3183. doi: 10.2174/15680266113136660224
    [88] Martinez JL, Sánchez MB, Martinez-Solano L, et al. (2009) Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. FEMS Microbiol Rev 33: 430–449. doi: 10.1111/j.1574-6976.2008.00157.x
    [89] Deak D, Outterson K, Powers JH, et al. (2016) Progress in the fight against multidrug-resistant bacteria? A review of U.S. Food and Drug Administration-approved antibiotics, 2010-2015. Ann Intern Med 165: 363–372.
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