Endopeptidase-Mediated Beta Lactam Tolerance

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Inhibition of bacterial cell wall synthesis by antibiotics such as penicillin can lead to unbalanced activity of a poorly defined set of lytic enzymes, termed ‘autolysins,’ which degrade the cell wall and typically cause cell lysis. Here, we report that in Vibrio cholerae (the cause of cholera), inhibition of cell wall synthesis results in the formation of viable spheres rather than cell lysis. Paradoxically, sphere formation requires the activity of cell wall degradative enzymes. Inhibition of cell wall synthesis in additional pathogens also leads to sphere formation. These findings expand our understanding of the cellular responses to cell wall acting antibiotics, demonstrating that cell wall degradative enzymes not only function as autolysins, but can also mediate cell survival in the face of cell wall insufficiency.

Vyšlo v časopise: Endopeptidase-Mediated Beta Lactam Tolerance. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004850
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004850

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Zdroje

1. Typas A, Banzhaf M, Gross CA, Vollmer W (2011) From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat Rev Microbiol 10: 123–136. doi: 10.1038/nrmicro2677 22203377

2. Tomasz A (1979) From penicillin-binding proteins to the lysis and death of bacteria: a 1979 view. Rev Infect Dis 1: 434–467. 45147

3. Tomasz A, Waks S (1975) Mechanism of action of penicillin: triggering of the pneumococcal autolytic enzyme by inhibitors of cell wall synthesis. Proc Natl Acad Sci U S A 72: 4162–4166. 674

4. Kitano K, Tomasz A (1979) Triggering of autolytic cell wall degradation in Escherichia coli by beta-lactam antibiotics. Antimicrob Agents Chemother 16: 838–848. 93877

5. Scheurwater E, Reid CW, Clarke AJ (2008) Lytic transglycosylases: bacterial space-making autolysins. Int J Biochem Cell Biol 40: 586–591. 17468031

6. Lee TK, Huang KC (2013) The role of hydrolases in bacterial cell-wall growth. Curr Opin Microbiol 16: 760–766. doi: 10.1016/j.mib.2013.08.005 24035761

7. Uehara T, Bernhardt TG (2011) More than just lysins: peptidoglycan hydrolases tailor the cell wall. Curr Opin Microbiol 14: 698–703. doi: 10.1016/j.mib.2011.10.003 22055466

8. Wyckoff TJ, Taylor JA, Salama NR Beyond growth: novel functions for bacterial cell wall hydrolases. Trends Microbiol 20: 540–547. doi: 10.1016/j.tim.2012.08.003 22944244

9. Kitano K, Tuomanen E, Tomasz A (1986) Transglycosylase and endopeptidase participate in the degradation of murein during autolysis of Escherichia coli. J Bacteriol 167: 759–765. 2875060

10. Chung HS, Yao Z, Goehring NW, Kishony R, Beckwith J, et al. (2009) Rapid beta-lactam-induced lysis requires successful assembly of the cell division machinery. Proc Natl Acad Sci U S A 106: 21872–21877. doi: 10.1073/pnas.0911674106 19995973

11. Yao Z, Kahne D, Kishony R (2012) Distinct single-cell morphological dynamics under beta-lactam antibiotics. Mol Cell 48: 705–712. doi: 10.1016/j.molcel.2012.09.016 23103254

12. Heidrich C, Templin MF, Ursinus A, Merdanovic M, Berger J, et al. (2001) Involvement of N-acetylmuramyl-L-alanine amidases in cell separation and antibiotic-induced autolysis of Escherichia coli. Mol Microbiol 41: 167–178. 11454209

13. Bonis M, Williams A, Guadagnini S, Werts C, Boneca IG (2012) The effect of bulgecin A on peptidoglycan metabolism and physiology of Helicobacter pylori. Microb Drug Resist 18: 230–239. doi: 10.1089/mdr.2011.0231 22432710

14. Templin MF, Edwards DH, Holtje JV (1992) A murein hydrolase is the specific target of bulgecin in Escherichia coli. J Biol Chem 267: 20039–20043. 1400320

15. Meisel U, Holtje JV, Vollmer W (2003) Overproduction of inactive variants of the murein synthase PBP1B causes lysis in Escherichia coli. J Bacteriol 185: 5342–5348. 12949085

16. Finley RL, Collignon P, Larsson DG, McEwen SA, Li XZ, et al. (2013) The scourge of antibiotic resistance: the important role of the environment. Clin Infect Dis 57: 704–710. doi: 10.1093/cid/cit355 23723195

17. Gerdes K, Maisonneuve E (2012) Bacterial persistence and toxin-antitoxin loci. Annu Rev Microbiol 66: 103–123. doi: 10.1146/annurev-micro-092611-150159 22994490

18. Keren I, Shah D, Spoering A, Kaldalu N, Lewis K (2004) Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli. J Bacteriol 186: 8172–8180. 15576765

19. Lewis K (2010) Persister cells. Annu Rev Microbiol 64: 357–372. doi: 10.1146/annurev.micro.112408.134306 20528688

20. Tuomanen E, Gilbert K, Tomasz A (1986) Modulation of bacteriolysis by cooperative effects of penicillin-binding proteins 1a and 3 in Escherichia coli. Antimicrob Agents Chemother 30: 659–663. 3541782

21. Errington J (2013) L-form bacteria, cell walls and the origins of life. Open Biol 3: 120143. doi: 10.1098/rsob.120143 23303308

22. Billings G, Ouzounov N, Ursell T, Desmarais SM, Shaevitz J, et al. (2014) De novo morphogenesis in L-forms via geometric control of cell growth. Mol Microbiol 93: 883–896. doi: 10.1111/mmi.12703 24995493

23. Kuru E, Hughes HV, Brown PJ, Hall E, Tekkam S, et al. (2012) In Situ probing of newly synthesized peptidoglycan in live bacteria with fluorescent D-amino acids. Angew Chem Int Ed Engl 51: 12519–12523. doi: 10.1002/anie.201206749 23055266

24. Cava F, de Pedro MA, Lam H, Davis BM, Waldor MK (2011) Distinct pathways for modification of the bacterial cell wall by non-canonical D-amino acids. EMBO J 30: 3442–3453. doi: 10.1038/emboj.2011.246 21792174

25. Dorr T, Cava F, Lam H, Davis BM, Waldor MK (2013) Substrate specificity of an elongation-specific peptidoglycan endopeptidase and its implications for cell wall architecture and growth of Vibrio cholerae. Mol Microbiol 89: 949–962. doi: 10.1111/mmi.12323 23834664

26. Dorr T, Moll A, Chao MC, Cava F, Lam H, et al. (2014) Differential requirement for PBP1a and PBP1b in in vivo and in vitro fitness of Vibrio cholerae. Infect Immun 82: 2115–2124. doi: 10.1128/IAI.00012-14 24614657

27. Dorr T, Lam H, Alvarez L, Cava F, Davis BM, et al. (2014) A novel peptidoglycan binding protein crucial for PBP1A-mediated cell wall biogenesis in Vibrio cholerae. PLoS Genet 10: e1004433. doi: 10.1371/journal.pgen.1004433 24945690

28. Moll A, Dorr T, Alvarez L, Chao MC, Davis BM, et al. (2014) Cell separation in Vibrio cholerae is mediated by a single amidase whose action is modulated by two non-redundant activators. J Bacteriol.

29. Peters NT, Dinh T, Bernhardt TG (2011) A fail-safe mechanism in the septal ring assembly pathway generated by the sequential recruitment of cell separation amidases and their activators. J Bacteriol 193: 4973–4983. doi: 10.1128/JB.00316-11 21764913

30. Uehara T, Parzych KR, Dinh T, Bernhardt TG (2010) Daughter cell separation is controlled by cytokinetic ring-activated cell wall hydrolysis. EMBO J 29: 1412–1422. doi: 10.1038/emboj.2010.36 20300061

31. Cho H, Uehara T, Bernhardt TG (2014) Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery. Cell 159: 1300–1311. doi: 10.1016/j.cell.2014.11.017 25480295

32. Jorgenson MA, Chen Y, Yahashiri A, Popham DL, Weiss DS (2014) The bacterial septal ring protein RlpA is a lytic transglycosylase that contributes to rod shape and daughter cell separation in Pseudomonas aeruginosa. Mol Microbiol 93: 113–128. doi: 10.1111/mmi.12643 24806796

33. Heidrich C, Ursinus A, Berger J, Schwarz H, Holtje JV (2002) Effects of multiple deletions of murein hydrolases on viability, septum cleavage, and sensitivity to large toxic molecules in Escherichia coli. J Bacteriol 184: 6093–6099. 12399477

34. Monahan LG, Turnbull L, Osvath SR, Birch D, Charles IG, et al. (2014) Rapid conversion of Pseudomonas aeruginosa to a spherical cell morphotype facilitates tolerance to carbapenems and penicillins but increases susceptibility to antimicrobial peptides. Antimicrob Agents Chemother 58: 1956–1962. doi: 10.1128/AAC.01901-13 24419348

35. Roberts D, Higgs E, Rutman A, Cole P (1984) Isolation of spheroplastic forms of Haemophilus influenzae from sputum in conventionally treated chronic bronchial sepsis using selective medium supplemented with N-acetyl-D-glucosamine: possible reservoir for re-emergence of infection. Br Med J (Clin Res Ed) 289: 1409–1412. 6437576

36. Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA 3rd, et al. (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 6: 343–345. doi: 10.1038/nmeth.1318 19363495

37. Ritchie JM, Rui H, Bronson RT, Waldor MK (2010) Back to the future: studying cholera pathogenesis using infant rabbits. MBio 1.