Role of endopeptidases in peptidoglycan synthesis mediated by alternative cross-linking enzymes in Escherichia coli.
Anti-Bacterial Agents
/ pharmacology
Catalysis
Endopeptidases
/ chemistry
Enzyme Activation
Escherichia coli
/ drug effects
Escherichia coli Proteins
/ chemistry
Gene Expression Regulation, Bacterial
Gene Expression Regulation, Enzymologic
Hydrolysis
Mass Spectrometry
Membrane Proteins
/ genetics
Mutation
Peptidoglycan
/ biosynthesis
Peptidyl Transferases
/ genetics
beta-Lactam Resistance
Escherichia coli
L,D-transpeptidase
endopeptidase
peptidoglycan
β-lactam
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
revised:
22
07
2021
received:
26
02
2021
accepted:
24
07
2021
pubmed:
13
8
2021
medline:
15
12
2021
entrez:
12
8
2021
Statut:
ppublish
Résumé
Bacteria resist to the turgor pressure of the cytoplasm through a net-like macromolecule, the peptidoglycan, made of glycan strands connected via peptides cross-linked by penicillin-binding proteins (PBPs). We recently reported the emergence of β-lactam resistance resulting from a bypass of PBPs by the YcbB L,D-transpeptidase (LdtD), which form chemically distinct 3→3 cross-links compared to 4→3 formed by PBPs. Here we show that peptidoglycan expansion requires controlled hydrolysis of cross-links and identify among eight endopeptidase paralogues the minimum enzyme complements essential for bacterial growth with 4→3 (MepM) and 3→3 (MepM and MepK) cross-links. Purified Mep endopeptidases unexpectedly displayed a 4→3 and 3→3 dual specificity implying recognition of a common motif in the two cross-link types. Uncoupling of the polymerization of glycan chains from the 4→3 cross-linking reaction was found to facilitate the bypass of PBPs by YcbB. These results illustrate the plasticity of the peptidoglycan polymerization machinery in response to the selective pressure of β-lactams.
Identifiants
pubmed: 34382698
doi: 10.15252/embj.2021108126
pmc: PMC8488565
doi:
Substances chimiques
Anti-Bacterial Agents
0
Blr protein, E coli
0
Escherichia coli Proteins
0
Membrane Proteins
0
Peptidoglycan
0
Peptidyl Transferases
EC 2.3.2.12
YcbB protein, E coli
EC 2.3.2.12
Endopeptidases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e108126Informations de copyright
© 2021 The Authors.
Références
Elife. 2018 Oct 16;7:
pubmed: 30324906
Nucleic Acids Res. 2017 Apr 20;45(7):3615-3626
pubmed: 28334756
EMBO J. 2021 Oct 1;40(19):e108126
pubmed: 34382698
PLoS Genet. 2017 Jul 27;13(7):e1006934
pubmed: 28749938
J Bacteriol. 2008 Jul;190(13):4782-5
pubmed: 18456808
Proc Natl Acad Sci U S A. 2019 Apr 16;116(16):7825-7830
pubmed: 30940749
J Bacteriol. 1999 Jul;181(13):3981-93
pubmed: 10383966
Mol Microbiol. 2020 Dec;114(6):966-978
pubmed: 32866331
J Bacteriol. 2008 Jun;190(11):3914-22
pubmed: 18390656
Mol Microbiol. 2012 Dec;86(5):1036-51
pubmed: 23062283
J Bacteriol. 1997 Oct;179(19):6112-21
pubmed: 9324260
J Bacteriol. 2009 Aug;191(16):5094-107
pubmed: 19525345
Mol Microbiol. 1992 May;6(9):1105-14
pubmed: 1375309
FEMS Microbiol Rev. 2021 Jan 8;45(1):
pubmed: 32897324
mBio. 2020 Mar 3;11(2):
pubmed: 32127458
Cell. 2014 Dec 4;159(6):1300-11
pubmed: 25480295
Mol Syst Biol. 2006;2:2006.0008
pubmed: 16738554
Biochemistry. 2007 Jan 9;46(1):120-8
pubmed: 17198381
J Bacteriol. 1985 Jan;161(1):238-42
pubmed: 3881387
Nature. 2000 Jan 20;403(6767):335-8
pubmed: 10659856
Biochimie. 2001 Jan;83(1):103-8
pubmed: 11254982
Mol Microbiol. 1992 May;6(9):1219-29
pubmed: 1375310
mBio. 2016 Feb 23;7(1):e00047-16
pubmed: 26908573
J Biol Chem. 1991 Feb 25;266(6):3760-7
pubmed: 1899866
Nat Commun. 2019 Apr 23;10(1):1849
pubmed: 31015395
J Bacteriol. 2011 Dec;193(24):6887-94
pubmed: 22001512
EMBO J. 2020 Mar 2;39(5):e102246
pubmed: 32009249
Mol Microbiol. 1991 Mar;5(3):675-84
pubmed: 2046551
Subcell Biochem. 2019;92:127-168
pubmed: 31214986
FEMS Microbiol Rev. 2008 Mar;32(2):234-58
pubmed: 18266856
mBio. 2019 Feb 5;10(1):
pubmed: 30723128
J Bacteriol. 2002 Nov;184(22):6093-9
pubmed: 12399477
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
pubmed: 10829079
J Bacteriol. 2005 Mar;187(5):1591-603
pubmed: 15716429
Microbiol Mol Biol Rev. 2011 Dec;75(4):636-63
pubmed: 22126997
J Bacteriol. 1979 Sep;139(3):770-4
pubmed: 383691
Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):10956-61
pubmed: 26283368
mBio. 2017 Oct 17;8(5):
pubmed: 29042497
Bioinformatics. 2009 Oct 15;25(20):2741-2
pubmed: 19740912
Ann N Y Acad Sci. 2013 Jan;1277:54-75
pubmed: 23163477
Mol Microbiol. 2012 Dec;86(5):1031-5
pubmed: 23066944
J Biol Chem. 2005 Nov 18;280(46):38146-52
pubmed: 16144833
J Biol Chem. 1988 Jul 25;263(21):10088-95
pubmed: 3292521
Appl Microbiol Biotechnol. 1992 Sep;37(6):772-83
pubmed: 1369491
Eur J Biochem. 1994 Sep 1;224(2):597-604
pubmed: 7925376
Elife. 2016 Oct 21;5:
pubmed: 27767957
Mol Microbiol. 2010 Nov;78(4):809-19
pubmed: 20815828
J Bacteriol. 1989 Nov;171(11):5783-94
pubmed: 2681142
Mol Microbiol. 2014 Mar;91(5):862-74
pubmed: 24405365
Antimicrob Agents Chemother. 2015 May;59(5):2785-90
pubmed: 25733506
Microbiology (Reading). 2013 Sep;159(Pt 9):1842-1852
pubmed: 23832002
J Am Soc Mass Spectrom. 2021 Apr 7;32(4):1138-1141
pubmed: 33683899
FEMS Microbiol Rev. 2008 Mar;32(2):386-408
pubmed: 18266857
Curr Opin Microbiol. 2017 Apr;36:55-61
pubmed: 28214390
Methods Mol Biol. 2014;1151:165-88
pubmed: 24838886