Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in <named-content content-type="genus-species">Listeria monocytogenes</named-content>

ABSTRACT Rod-shaped bacteria have two modes of peptidoglycan synthesis: lateral synthesis and synthesis at the cell division site. These two processes are controlled by two macromolecular protein complexes, the elongasome and divisome. Recently, it has been shown that the Bacillus subtilis RodA prot...

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Autores principales:	Jeanine Rismondo, Sven Halbedel, Angelika Gründling
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	FtsW Listeria monocytogenes RodA SEDS antibiotic resistance cell division Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1d67ac05b4914edfb122a52761f8f062
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spelling	oai:doaj.org-article:1d67ac05b4914edfb122a52761f8f0622021-11-15T16:22:10ZCell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in <named-content content-type="genus-species">Listeria monocytogenes</named-content>10.1128/mBio.01448-192150-7511https://doaj.org/article/1d67ac05b4914edfb122a52761f8f0622019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01448-19https://doaj.org/toc/2150-7511ABSTRACT Rod-shaped bacteria have two modes of peptidoglycan synthesis: lateral synthesis and synthesis at the cell division site. These two processes are controlled by two macromolecular protein complexes, the elongasome and divisome. Recently, it has been shown that the Bacillus subtilis RodA protein, which forms part of the elongasome, has peptidoglycan glycosyltransferase activity. The cell division-specific RodA homolog FtsW fulfils a similar role at the divisome. The human pathogen Listeria monocytogenes carries genes that encode up to six FtsW/RodA homologs; however, their functions have not yet been investigated. Analysis of deletion and depletion strains led to the identification of the essential cell division-specific FtsW protein, FtsW1. Interestingly, L. monocytogenes carries a gene that encodes a second FtsW protein, FtsW2, which can compensate for the lack of FtsW1, when expressed from an inducible promoter. L. monocytogenes also possesses three RodA homologs, RodA1, RodA2, and RodA3, and their combined absence is lethal. Cells of a rodA1 rodA3 double mutant are shorter and have increased antibiotic and lysozyme sensitivity, probably due to a weakened cell wall. Results from promoter activity assays revealed that expression of rodA3 and ftsW2 is induced in the presence of antibiotics targeting penicillin binding proteins. Consistent with this, a rodA3 mutant was more susceptible to the β-lactam antibiotic cefuroxime. Interestingly, overexpression of RodA3 also led to increased cefuroxime sensitivity. Our study highlights that L. monocytogenes genes encode a multitude of functional FtsW and RodA enzymes to produce its rigid cell wall and that their expression needs to be tightly regulated to maintain growth, cell division, and antibiotic resistance. IMPORTANCE The human pathogen Listeria monocytogenes is usually treated with high doses of β-lactam antibiotics, often combined with gentamicin. However, these antibiotics only act bacteriostatically on L. monocytogenes, and the immune system is needed to clear the infection. Therefore, individuals with a compromised immune system are at risk to develop a severe form of Listeria infection, which can be fatal in up to 30% of cases. The development of new strategies to treat Listeria infections is necessary. Here we show that the expression of some of the FtsW and RodA enzymes of L. monocytogenes is induced by the presence of β-lactam antibiotics, and the combined absence of these enzymes makes bacteria more susceptible to this class of antibiotics. The development of antimicrobial agents that inhibit the activity or production of FtsW and RodA enzymes might therefore help to improve the treatment of Listeria infections and thereby lead to a reduction in mortality.Jeanine RismondoSven HalbedelAngelika GründlingAmerican Society for MicrobiologyarticleFtsWListeria monocytogenesRodASEDSantibiotic resistancecell divisionMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	FtsW Listeria monocytogenes RodA SEDS antibiotic resistance cell division Microbiology QR1-502
spellingShingle	FtsW Listeria monocytogenes RodA SEDS antibiotic resistance cell division Microbiology QR1-502 Jeanine Rismondo Sven Halbedel Angelika Gründling Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in <named-content content-type="genus-species">Listeria monocytogenes</named-content>
description	ABSTRACT Rod-shaped bacteria have two modes of peptidoglycan synthesis: lateral synthesis and synthesis at the cell division site. These two processes are controlled by two macromolecular protein complexes, the elongasome and divisome. Recently, it has been shown that the Bacillus subtilis RodA protein, which forms part of the elongasome, has peptidoglycan glycosyltransferase activity. The cell division-specific RodA homolog FtsW fulfils a similar role at the divisome. The human pathogen Listeria monocytogenes carries genes that encode up to six FtsW/RodA homologs; however, their functions have not yet been investigated. Analysis of deletion and depletion strains led to the identification of the essential cell division-specific FtsW protein, FtsW1. Interestingly, L. monocytogenes carries a gene that encodes a second FtsW protein, FtsW2, which can compensate for the lack of FtsW1, when expressed from an inducible promoter. L. monocytogenes also possesses three RodA homologs, RodA1, RodA2, and RodA3, and their combined absence is lethal. Cells of a rodA1 rodA3 double mutant are shorter and have increased antibiotic and lysozyme sensitivity, probably due to a weakened cell wall. Results from promoter activity assays revealed that expression of rodA3 and ftsW2 is induced in the presence of antibiotics targeting penicillin binding proteins. Consistent with this, a rodA3 mutant was more susceptible to the β-lactam antibiotic cefuroxime. Interestingly, overexpression of RodA3 also led to increased cefuroxime sensitivity. Our study highlights that L. monocytogenes genes encode a multitude of functional FtsW and RodA enzymes to produce its rigid cell wall and that their expression needs to be tightly regulated to maintain growth, cell division, and antibiotic resistance. IMPORTANCE The human pathogen Listeria monocytogenes is usually treated with high doses of β-lactam antibiotics, often combined with gentamicin. However, these antibiotics only act bacteriostatically on L. monocytogenes, and the immune system is needed to clear the infection. Therefore, individuals with a compromised immune system are at risk to develop a severe form of Listeria infection, which can be fatal in up to 30% of cases. The development of new strategies to treat Listeria infections is necessary. Here we show that the expression of some of the FtsW and RodA enzymes of L. monocytogenes is induced by the presence of β-lactam antibiotics, and the combined absence of these enzymes makes bacteria more susceptible to this class of antibiotics. The development of antimicrobial agents that inhibit the activity or production of FtsW and RodA enzymes might therefore help to improve the treatment of Listeria infections and thereby lead to a reduction in mortality.
format	article
author	Jeanine Rismondo Sven Halbedel Angelika Gründling
author_facet	Jeanine Rismondo Sven Halbedel Angelika Gründling
author_sort	Jeanine Rismondo
title	Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in <named-content content-type="genus-species">Listeria monocytogenes</named-content>
title_short	Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in <named-content content-type="genus-species">Listeria monocytogenes</named-content>
title_full	Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in <named-content content-type="genus-species">Listeria monocytogenes</named-content>
title_fullStr	Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in <named-content content-type="genus-species">Listeria monocytogenes</named-content>
title_full_unstemmed	Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in <named-content content-type="genus-species">Listeria monocytogenes</named-content>
title_sort	cell shape and antibiotic resistance are maintained by the activity of multiple ftsw and roda enzymes in <named-content content-type="genus-species">listeria monocytogenes</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/1d67ac05b4914edfb122a52761f8f062
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Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in <named-content content-type="genus-species">Listeria monocytogenes</named-content>

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