A CozE Homolog Contributes to Cell Size Homeostasis of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>

ABSTRACT Control of peptidoglycan assembly is critical to maintain bacterial cell size and morphology. Penicillin-binding proteins (PBPs) are crucial enzymes for the polymerization of the glycan strand and/or their cross-linking via peptide branches. Over the last few years, it has become clear that...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Gro Anita Stamsås, Marine Restelli, Adrien Ducret, Céline Freton, Pierre Simon Garcia, Leiv Sigve Håvarstein, Daniel Straume, Christophe Grangeasse, Morten Kjos
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	cell division morphogenesis penicillin-binding proteins peptidoglycan Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bedf7cb8192d4e2b8674bb24edb4f074
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bedf7cb8192d4e2b8674bb24edb4f074
record_format	dspace
spelling	oai:doaj.org-article:bedf7cb8192d4e2b8674bb24edb4f0742021-11-15T16:19:09ZA CozE Homolog Contributes to Cell Size Homeostasis of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>10.1128/mBio.02461-202150-7511https://doaj.org/article/bedf7cb8192d4e2b8674bb24edb4f0742020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02461-20https://doaj.org/toc/2150-7511ABSTRACT Control of peptidoglycan assembly is critical to maintain bacterial cell size and morphology. Penicillin-binding proteins (PBPs) are crucial enzymes for the polymerization of the glycan strand and/or their cross-linking via peptide branches. Over the last few years, it has become clear that PBP activity and localization can be regulated by specific cognate regulators. The first regulator of PBP activity in Gram-positive bacteria was discovered in the human pathogen Streptococcus pneumoniae. This regulator, named CozE, controls the activity of the bifunctional PBP1a to promote cell elongation and achieve a proper cell morphology. In this work, we studied a previously undescribed CozE homolog in the pneumococcus, which we named CozEb. This protein displays the same membrane organization as CozE but is much more widely conserved among Streptococcaceae genomes. Interestingly, cozEb deletion results in cells that are smaller than their wild-type counterparts, which is the opposite effect of cozE deletion. Furthermore, double deletion of cozE and cozEb results in poor viability and exacerbated cell shape defects. Coimmunoprecipitation further showed that CozEb is part of the same complex as CozE and PBP1a. However, although we confirmed that CozE is required for septal localization of PBP1a, the absence of CozEb has no effect on PBP1a localization. Nevertheless, we found that the overexpression of CozEb can compensate for the absence of CozE in all our assays. Altogether, our results show that the interplay between PBP1a and the cell size regulators CozE and CozEb is required for the maintenance of pneumococcal cell size and shape. IMPORTANCE Penicillin-binding proteins (PBPs), the proteins catalyzing the last steps of peptidoglycan assembly, are critical for bacteria to maintain cell size, shape, and integrity. PBPs are consequently attractive targets for antibiotics. Resistance to antibiotics in Streptococcus pneumoniae (the pneumococcus) are often associated with mutations in the PBPs. In this work, we describe a new protein, CozEb, controlling the cell size of pneumococcus. CozEb is a highly conserved integral membrane protein that works together with other proteins to regulate PBPs and peptidoglycan synthesis. Deciphering the intricate mechanisms by which the pneumococcus controls peptidoglycan assembly might allow the design of innovative anti-infective strategies, for example, by resensitizing resistant strains to PBP-targeting antibiotics.Gro Anita StamsåsMarine RestelliAdrien DucretCéline FretonPierre Simon GarciaLeiv Sigve HåvarsteinDaniel StraumeChristophe GrangeasseMorten KjosAmerican Society for Microbiologyarticlecell divisionmorphogenesispenicillin-binding proteinspeptidoglycanMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell division morphogenesis penicillin-binding proteins peptidoglycan Microbiology QR1-502
spellingShingle	cell division morphogenesis penicillin-binding proteins peptidoglycan Microbiology QR1-502 Gro Anita Stamsås Marine Restelli Adrien Ducret Céline Freton Pierre Simon Garcia Leiv Sigve Håvarstein Daniel Straume Christophe Grangeasse Morten Kjos A CozE Homolog Contributes to Cell Size Homeostasis of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
description	ABSTRACT Control of peptidoglycan assembly is critical to maintain bacterial cell size and morphology. Penicillin-binding proteins (PBPs) are crucial enzymes for the polymerization of the glycan strand and/or their cross-linking via peptide branches. Over the last few years, it has become clear that PBP activity and localization can be regulated by specific cognate regulators. The first regulator of PBP activity in Gram-positive bacteria was discovered in the human pathogen Streptococcus pneumoniae. This regulator, named CozE, controls the activity of the bifunctional PBP1a to promote cell elongation and achieve a proper cell morphology. In this work, we studied a previously undescribed CozE homolog in the pneumococcus, which we named CozEb. This protein displays the same membrane organization as CozE but is much more widely conserved among Streptococcaceae genomes. Interestingly, cozEb deletion results in cells that are smaller than their wild-type counterparts, which is the opposite effect of cozE deletion. Furthermore, double deletion of cozE and cozEb results in poor viability and exacerbated cell shape defects. Coimmunoprecipitation further showed that CozEb is part of the same complex as CozE and PBP1a. However, although we confirmed that CozE is required for septal localization of PBP1a, the absence of CozEb has no effect on PBP1a localization. Nevertheless, we found that the overexpression of CozEb can compensate for the absence of CozE in all our assays. Altogether, our results show that the interplay between PBP1a and the cell size regulators CozE and CozEb is required for the maintenance of pneumococcal cell size and shape. IMPORTANCE Penicillin-binding proteins (PBPs), the proteins catalyzing the last steps of peptidoglycan assembly, are critical for bacteria to maintain cell size, shape, and integrity. PBPs are consequently attractive targets for antibiotics. Resistance to antibiotics in Streptococcus pneumoniae (the pneumococcus) are often associated with mutations in the PBPs. In this work, we describe a new protein, CozEb, controlling the cell size of pneumococcus. CozEb is a highly conserved integral membrane protein that works together with other proteins to regulate PBPs and peptidoglycan synthesis. Deciphering the intricate mechanisms by which the pneumococcus controls peptidoglycan assembly might allow the design of innovative anti-infective strategies, for example, by resensitizing resistant strains to PBP-targeting antibiotics.
format	article
author	Gro Anita Stamsås Marine Restelli Adrien Ducret Céline Freton Pierre Simon Garcia Leiv Sigve Håvarstein Daniel Straume Christophe Grangeasse Morten Kjos
author_facet	Gro Anita Stamsås Marine Restelli Adrien Ducret Céline Freton Pierre Simon Garcia Leiv Sigve Håvarstein Daniel Straume Christophe Grangeasse Morten Kjos
author_sort	Gro Anita Stamsås
title	A CozE Homolog Contributes to Cell Size Homeostasis of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_short	A CozE Homolog Contributes to Cell Size Homeostasis of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_full	A CozE Homolog Contributes to Cell Size Homeostasis of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_fullStr	A CozE Homolog Contributes to Cell Size Homeostasis of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_full_unstemmed	A CozE Homolog Contributes to Cell Size Homeostasis of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_sort	coze homolog contributes to cell size homeostasis of <named-content content-type="genus-species">streptococcus pneumoniae</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/bedf7cb8192d4e2b8674bb24edb4f074
work_keys_str_mv	AT groanitastamsas acozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT marinerestelli acozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT adrienducret acozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT celinefreton acozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT pierresimongarcia acozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT leivsigvehavarstein acozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT danielstraume acozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT christophegrangeasse acozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT mortenkjos acozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT groanitastamsas cozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT marinerestelli cozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT adrienducret cozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT celinefreton cozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT pierresimongarcia cozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT leivsigvehavarstein cozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT danielstraume cozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT christophegrangeasse cozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent AT mortenkjos cozehomologcontributestocellsizehomeostasisofnamedcontentcontenttypegenusspeciesstreptococcuspneumoniaenamedcontent
_version_	1718426928816324608

A CozE Homolog Contributes to Cell Size Homeostasis of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>

Ejemplares similares