Antibiotic resistance as a stress response: Recovery of high-level oxacillin resistance in methicillin-resistant Staphylococcus aureus “auxiliary” (fem) mutants by induction of the stringent stress response

Antimicrobial Agents and Chemotherapy

Volumn 61, Issue 8, 2017, Pages

  Kim, Choon Keun ^a,c   Milheiriço, Catarina ^a,b   De Lencastre, Hermínia ^a,b   Tomasza, Alexander ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

^b INSTITUTO DE TECNOLOGIA QUÍMICA E BIOLÓGICA   (Portugal)

^c UNIVERSITY OF NOTRE DAME   (United States)

Author keywords

Auxiliary genes; Oxacillin resistance expression; Stress response

Indexed keywords

OXACILLIN; PENICILLIN BINDING PROTEIN 2A; PSEUDOMONIC ACID; ANTIINFECTIVE AGENT; BACTERIAL PROTEIN; DNA DIRECTED RNA POLYMERASE; FEMA PROTEIN, BACTERIA; MECA PROTEIN, STAPHYLOCOCCUS AUREUS; METICILLIN; PENICILLIN BINDING PROTEIN;

ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GENE; BACTERIUM MUTANT; CELL MEMBRANE; CONTROLLED STUDY; GENE MUTATION; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MINIMUM INHIBITORY CONCENTRATION; MUTAGENESIS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; STRESS; TITRIMETRY; BACTERIAL GENOME; BIOSYNTHESIS; GENETICS; MICROBIAL SENSITIVITY TEST; MULTIDRUG RESISTANCE;

ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; DNA-DIRECTED RNA POLYMERASES; DRUG RESISTANCE, MULTIPLE, BACTERIAL; GENOME, BACTERIAL; METHICILLIN; METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS; MICROBIAL SENSITIVITY TESTS; MUPIROCIN; OXACILLIN; PENICILLIN-BINDING PROTEINS;

EID: 85026408601     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00313-17     Document Type: Article

References (32)

1. Hackbarth CJ, Chambers HF. 1993. blaI and blaR1 regulate beta-lactamase and PBP 2a production in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 37:1144–1149. https://doi.org/10.1128/AAC.37.5.1144.
2. Hiramatsu K, Asada K, Suzuki E, Okonogi K, Yokota T. 1992. Molecular cloning and nucleotide sequence determination of the regulator region of mecA gene in methicillin-resistant Staphylococcus aureus (MRSA). FEBS Lett 298:133–136. https://doi.org/10.1016/0014-5793(92)80039-J.
3. de Lencastre H, Tomasz A. 1994. Reassessment of the number of auxiliary genes essential for expression of high-level methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother 38:2590–2598. https://doi.org/10.1128/AAC.38.11.2590.
4. Berger-Bächi B. 1983. Insertional inactivation of staphylococcal methicillin resistance by Tn551. J Bacteriol 154:479–487.
5. Kornblum J, Hartman BJ, Novick RP, Tomasz A. 1986. Conversion of a homogeneously methicillin-resistant strain of Staphylococcus aureus to heterogeneous resistance by Tn551-mediated insertional inactivation. Eur J Clin Microbiol 5:714–718. https://doi.org/10.1007/BF02013311.
6. De Lencastre H, Wu SW, Pinho MG, Ludovice AM, Filipe S, Gardete S, Sobral R, Gill S, Chung M, Tomasz A. 1999. Antibiotic resistance as a stress response: complete sequencing of a large number of chromosomal loci in Staphylococcus aureus strain COL that impact on the expression of resistance to methicillin. Microb Drug Resist 5:163–175. https://doi.org/10.1089/mdr.1999.5.163.
7. Chung M, Antignac A, Kim C, Tomasz A. 2008. Comparative study of the susceptibilities of major epidemic clones of methicillin-resistant Staphylococcus aureus to oxacillin and to the new broad-spectrum cephalo-sporin ceftobiprole. Antimicrob Agents Chemother 52:2709–2717. https://doi.org/10.1128/AAC.00266-08.
8. Tomasz A, Nachman S, Leaf H. 1991. Stable classes of phenotypic expression in methicillin-resistant clinical isolates of staphylococci. Antimicrob Agents Chemother 35:124 –129. https://doi.org/10.1128/AAC.35.1.124.
9. de Lencastre H, Figueiredo AM, Tomasz A. 1993. Genetic control of population structure in heterogeneous strains of methicillin resistant Staphylococcus aureus. Eur J Clin Microbiol Infect Dis 12(Suppl 1): S13–S18. https://doi.org/10.1007/BF02389872.
10. Oliveira DC, Tomasz A, de Lencastre H. 2001. The evolution of pandemic clones of methicillin-resistant Staphylococcus aureus: identification of two ancestral genetic backgrounds and the associated mec elements. Microb Drug Resist 7:349–361. https://doi.org/10.1089/10766290152773365.
11. Kim C, Mwangi M, Chung M, Milheirico C, de Lencastre H, Tomasz A. 2013. The mechanism of heterogeneous beta-lactam resistance in MRSA: key role of the stringent stress response. PLoS One 8:e82814. https://doi.org/10.1371/journal.pone.0082814.
12. Dordel J, Kim C, Chung M, Pardos de la Gandara M, Holden MT, Parkhill J, de Lencastre H, Bentley SD, Tomasz A. 2014. Novel determinants of antibiotic resistance: identification of mutated loci in highly methicillin-resistant subpopulations of methicillin-resistant Staphylococcus aureus. mBio 5(2):e01000-13. https://doi.org/10.1128/mBio.01000-13.
13. Aedo S, Tomasz A. 2016. Role of the stringent stress response in the antibiotic resistance phenotype of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 60:2311–2317. https://doi.org/10.1128/AAC.02697-15.
14. Mwangi MM, Kim C, Chung M, Tsai J, Vijayadamodar G, Benitez M, Jarvie TP, Du L, Tomasz A. 2013. Whole-genome sequencing reveals a link between beta-lactam resistance and synthetases of the alarmone (p)ppGpp in Staphylococcus aureus. Microb Drug Resist 19:153–159. https://doi.org/10.1089/mdr.2013.0053.
15. Dalebroux ZD, Swanson MS. 2012. ppGpp: magic beyond RNA polymerase. Nat Rev Microbiol 10:203–212. https://doi.org/10.1038/nrmicro2720.
16. Shaw LN, Aish J, Davenport JE, Brown MC, Lithgow JK, Simmonite K, Crossley H, Travis J, Potempa J, Foster SJ. 2006. Investigations into sigmaB-modulated regulatory pathways governing extracellular virulence determinant production in Staphylococcus aureus. J Bacteriol 188:6070–6080. https://doi.org/10.1128/JB.00551-06.
17. Stapleton MR, Horsburgh MJ, Hayhurst EJ, Wright L, Jonsson IM, Tarkowski A, Kokai-Kun JF, Mond JJ, Foster SJ. 2007. Characterization of IsaA and SceD, two putative lytic transglycosylases of Staphylococcus aureus. J Bacteriol 189:7316–7325. https://doi.org/10.1128/JB.00734-07.
18. Singh VK, Schmidt JL, Jayaswal RK, Wilkinson BJ. 2003. Impact of sigB mutation on Staphylococcus aureus oxacillin and vancomycin resistance varies with parental background and method of assessment. Int J Antimicrob Agents 21:256 –261. https://doi.org/10.1016/S0924-8579(02)00359-X.
19. Wu S, de Lencastre H, Tomasz A. 1996. Sigma-B, a putative operon encoding alternate sigma factor of Staphylococcus aureus RNA polymerase: molecular cloning and DNA sequencing. J Bacteriol 178: 6036–6042. https://doi.org/10.1128/jb.178.20.6036-6042.1996.
20. Poole K. 2012. Bacterial stress responses as determinants of antimicrobial resistance. J Antimicrob Chemother 67:2069–2089. https://doi.org/10.1093/jac/dks196.
21. de Jonge BL, Chang YS, Gage D, Tomasz A. 1992. Peptidoglycan composition in heterogeneous Tn551 mutants of a methicillin-resistant Staphylococcus aureus strain. J Biol Chem 267:11255–11259.
22. de Jonge BL, Sidow T, Chang YS, Labischinski H, Berger-Bachi B, Gage DA, Tomasz A. 1993. Altered muropeptide composition in Staphylococcus aureus strains with an inactivated femA locus. J Bacteriol 175: 2779–2782. https://doi.org/10.1128/jb.175.9.2779-2782.1993.
23. Kim C, Mwangi M, Chung M, Milheirco C, de Lencastre H, Tomasz A. 2013. The mechanism of heterogeneous beta-lactam resistance in MRSA: key role of the stringent stress response. PLoS One 8:e82814. https://doi.org/10.1371/journal.pone.0082814.
24. García-Álvarez L, Holden MT, Lindsay H, Webb CR, Brown DF, Curran MD, Walpole E, Brooks K, Pickard DJ, Teale C, Parkhill J, Bentley SD, Edwards GF, Girvan EK, Kearns AM, Pichon B, Hill RL, Larsen AR, Skov RL, Peacock SJ, Maskell DJ, Holmes MA. 2011. Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study. Lancet Infect Dis 11:595– 603. https://doi.org/10.1016/S1473-3099(11)70126-8.
25. Couto I, Wu SW, Tomasz A, de Lencastre H. 2003. Development of methicillin resistance in clinical isolates of Staphylococcus sciuri by transcriptional activation of the mecA homologue native to S. sciuri. J Bacteriol 185:645–653. https://doi.org/10.1128/JB.185.2.645-653.2003.
26. Zhou Y, Antignac A, Wu SW, Tomasz A. 2008. Penicillin-binding proteins and cell wall composition in beta-lactam-sensitive and -resistant strains of Staphylococcus sciuri. J Bacteriol 190:508–514. https://doi.org/10.1128/JB.01549-07.
27. Rolo J, Worning P, Boye Nielsen J, Sobral R, Bowden R, Bouchami O, Damborg P, Guardabassi L, Perreten V, Westh H, Tomasz A, de Lencastre H, Miragaia M. 2017. Evidence for the evolutionary steps leading to mecA-mediated beta-lactam resistance in staphylococci. PLoS Genet 13:e1006674. https://doi.org/10.1371/journal.pgen.1006674.
28. Pinho MG, de Lencastre H, Tomasz A. 2000. Cloning, characterization, and inactivation of the gene pbpC, encoding penicillin-binding protein 3 of Staphylococcus aureus. J Bacteriol 182:1074–1079. https://doi.org/10.1128/JB.182.4.1074-1079.2000.
29. Tonin E, Tomasz A. 1986. Beta-lactam-specific resistant mutants of Staphylococcus aureus. Antimicrob Agents Chemother 30:577–583. https://doi.org/10.1128/AAC.30.4.577.
30. Roemer T, Schneider T, Pinho MG. 2013. Auxiliary factors: a chink in the armor of MRSA resistance to beta-lactam antibiotics. Curr Opin Microbiol 16:538 –548. https://doi.org/10.1016/j.mib.2013.06.012.
31. Sivakumari N, Chiranjeevi P, RPradhan D, Umamaheswari A. 2015. Discovery of potent inhibitors against GTP pyrophosphokinase of Neisseria meningitidis serogroup B. Int J Sci Eng Res 6:273–278.
32. Oshida T, Tomasz A. 1992. Isolation and characterization of a Tn551-autolysis mutant of Staphylococcus aureus. J Bacteriol 174:4952–4959. https://doi.org/10.1128/jb.174.15.4952-4959.1992.