Competence remodels the pneumococcal cell wall exposing key surface virulence factors that mediate increased host adherence.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, [2003]-

Streptococcus pneumoniae*/genetics ; Virulence Factors*/genetics ; Virulence Factors*/metabolism; Humans ; N-Acetylmuramoyl-L-alanine Amidase/chemistry ; N-Acetylmuramoyl-L-alanine Amidase/genetics ; N-Acetylmuramoyl-L-alanine Amidase/metabolism ; Choline/metabolism ; Cell Wall/metabolism ; Bacterial Proteins/metabolism

Competence development in the human pathogen Streptococcus pneumoniae controls several features such as genetic transformation, biofilm formation, and virulence. Competent bacteria produce so-called "fratricins" such as CbpD that kill noncompetent siblings by cleaving peptidoglycan (PGN). CbpD is a choline-binding protein (CBP) that binds to phosphorylcholine residues found on wall and lipoteichoic acids (WTA and LTA) that together with PGN are major constituents of the pneumococcal cell wall. Competent pneumococci are protected against fratricide by producing the immunity protein ComM. How competence and fratricide contribute to virulence is unknown. Here, using a genome-wide CRISPRi-seq screen, we show that genes involved in teichoic acid (TA) biosynthesis are essential during competence. We demonstrate that LytR is the major enzyme mediating the final step in WTA formation, and that, together with ComM, is essential for immunity against CbpD. Importantly, we show that key virulence factors PspA and PspC become more surface-exposed at midcell during competence, in a CbpD-dependent manner. Together, our work supports a model in which activation of competence is crucial for host adherence by increased surface exposure of its various CBPs.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Minhas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Microb Pathog. 2006 May;40(5):228-33. (PMID: 16540281)
Cell Host Microbe. 2020 Apr 8;27(4):544-555.e3. (PMID: 32130952)
Cell Microbiol. 2019 Nov;21(11):e13077. (PMID: 31251447)
J Bacteriol. 2008 Apr;190(7):2379-87. (PMID: 18245291)
Nat Genet. 2014 Mar;46(3):305-309. (PMID: 24509479)
PLoS Pathog. 2016 Feb 03;12(2):e1005422. (PMID: 26840404)
Infect Immun. 2018 Feb 20;86(3):. (PMID: 29263108)
J Exp Med. 2017 Jun 5;214(6):1619-1630. (PMID: 28515075)
J Exp Med. 1931 Oct 31;54(5):681-99. (PMID: 19869950)
Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11140-4. (PMID: 7479953)
Infect Immun. 2002 Jan;70(1):412-5. (PMID: 11748210)
Nucleic Acids Res. 2018 Nov 2;46(19):9990-10006. (PMID: 30165663)
Cell. 2000 Sep 15;102(6):827-37. (PMID: 11030626)
Nat Rev Microbiol. 2008 Apr;6(4):288-301. (PMID: 18340341)
Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):6129-6138. (PMID: 32123104)
Genome Biol. 2016 Sep 27;17(1):198. (PMID: 27678244)
J Bacteriol. 2009 Sep;191(18):5859-64. (PMID: 19581359)
J Bacteriol. 1991 Jan;173(1):372-81. (PMID: 1987129)
Proc Natl Acad Sci U S A. 2017 May 30;114(22):5695-5700. (PMID: 28495967)
Mol Microbiol. 1997 Sep;25(5):819-29. (PMID: 9364908)
Microbiology (Reading). 2009 Jul;155(Pt 7):2223-2234. (PMID: 19389766)
Front Immunol. 2019 Apr 09;10:723. (PMID: 31024555)
Nucleic Acids Res. 2018 Nov 2;46(19):9971-9989. (PMID: 30107613)
Cell. 2014 Apr 10;157(2):395-406. (PMID: 24725406)
Cell Host Microbe. 2021 Jan 13;29(1):107-120.e6. (PMID: 33120116)
Microb Drug Resist. 2012 Jun;18(3):344-58. (PMID: 22432701)
FEMS Microbiol Rev. 2009 May;33(3):572-86. (PMID: 19396958)
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7681-6. (PMID: 12032343)
Elife. 2020 Sep 23;9:. (PMID: 32965219)
Mol Microbiol. 1996 Aug;21(4):863-9. (PMID: 8878047)
Microb Drug Resist. 2012 Jun;18(3):240-55. (PMID: 22432711)
Nat Rev Microbiol. 2017 Oct;15(10):621-629. (PMID: 28690319)
Mol Syst Biol. 2017 May 10;13(5):931. (PMID: 28490437)
J Bacteriol. 2019 Jun 10;201(13):. (PMID: 30885934)
Mol Microbiol. 2006 Feb;59(4):1297-307. (PMID: 16430701)
Lancet Glob Health. 2018 Jul;6(7):e744-e757. (PMID: 29903376)
Nat Commun. 2017 Nov 20;8(1):1621. (PMID: 29158515)
Int J Mol Sci. 2021 Jan 18;22(2):. (PMID: 33477538)
Nat Rev Microbiol. 2018 Jun;16(6):355-367. (PMID: 29599457)
PLoS Pathog. 2022 Jun 22;18(6):e1010516. (PMID: 35731836)
Infect Immun. 2006 Feb;74(2):821-9. (PMID: 16428724)
Microbiology (Reading). 2017 Jan;163(1):9-21. (PMID: 27902435)
Nat Commun. 2017 Dec 12;8(1):2093. (PMID: 29233962)
Nat Microbiol. 2016 Jun 20;1(7):16077. (PMID: 27572972)
J Vis Exp. 2011 Jul 28;(53):. (PMID: 21841760)
Mol Microbiol. 2004 Feb;51(4):1051-70. (PMID: 14763980)
Elife. 2019 Apr 09;8:. (PMID: 30964003)
Microbiol Resour Announc. 2019 May 9;8(19):. (PMID: 31072896)
FEMS Microbiol Rev. 2009 May;33(3):643-56. (PMID: 19228200)
PeerJ. 2022 Oct 25;10:e14041. (PMID: 36312750)
Infect Immun. 2011 Nov;79(11):4550-8. (PMID: 21875962)
Nat Protoc. 2022 Feb;17(2):252-281. (PMID: 34997243)
J Biol Chem. 2004 Feb 20;279(8):6296-304. (PMID: 14660617)
Infect Immun. 2020 Mar 23;88(4):. (PMID: 31988172)
J Bacteriol. 1999 Aug;181(16):5004-16. (PMID: 10438773)
J Infect Dis. 2013 Feb 1;207(3):439-49. (PMID: 23175765)
Infect Immun. 1979 Feb;23(2):545-8. (PMID: 33904)
PLoS Pathog. 2019 Jul 29;15(7):e1007987. (PMID: 31356624)
Mol Microbiol. 2008 Jul;69(1):245-53. (PMID: 18485065)
EMBO J. 2011 Sep 30;30(24):4931-41. (PMID: 21964069)
J Biol Chem. 1975 Aug 10;250(15):6072-6. (PMID: 238995)
Infect Immun. 2000 Oct;68(10):5690-5. (PMID: 10992472)
Mol Microbiol. 1996 Aug;21(4):853-62. (PMID: 8878046)
PLoS Pathog. 2011 Sep;7(9):e1002241. (PMID: 21909280)
Nat Rev Microbiol. 2008 Apr;6(4):276-87. (PMID: 18327271)
Mol Microbiol. 2004 Feb;51(4):1071-86. (PMID: 14763981)
Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27608-27619. (PMID: 33087560)
J Bacteriol. 2005 Jul;187(13):4338-45. (PMID: 15968042)
Cell Surf. 2018 Jun 12;2:24-37. (PMID: 32743129)
PLoS Pathog. 2016 Feb 03;12(2):e1005413. (PMID: 26840124)
Genes (Basel). 2019 May 22;10(5):. (PMID: 31121970)
Nat Rev Microbiol. 2014 Mar;12(3):181-96. (PMID: 24509783)
Mol Microbiol. 2017 Jan;103(1):99-116. (PMID: 27684385)
Front Microbiol. 2018 Jun 13;9:1199. (PMID: 29951042)
Mol Microbiol. 2013 Jan;87(2):394-411. (PMID: 23216914)
Science. 1967 Aug 11;157(3789):694-7. (PMID: 4381896)
PLoS Pathog. 2018 Oct 11;14(10):e1007328. (PMID: 30308062)
Cell Rep. 2022 Dec 20;41(12):111851. (PMID: 36543127)
Mol Microbiol. 2010 Mar;75(6):1513-28. (PMID: 20180906)
Science. 2011 Jan 28;331(6016):430-4. (PMID: 21273480)
Mol Microbiol. 2010 May;76(4):905-17. (PMID: 20384696)
mBio. 2021 May 4;12(3):. (PMID: 33947761)

0 (Virulence Factors)
EC 3.5.1.28 (N-Acetylmuramoyl-L-alanine Amidase)
N91BDP6H0X (Choline)
0 (Bacterial Proteins)

Date Created: 20230130 Date Completed: 20230213 Latest Revision: 20230224

20250114

PMC9910801

10.1371/journal.pbio.3001990

36716340