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Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance

2015-05-07Journal article Open access
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dc.contributor.authorReed, Patricia
dc.contributor.authorAtilano, Magda L.
dc.contributor.authorAlves, Renato
dc.contributor.authorHoiczyk, Egbert
dc.contributor.authorSher, Xinwei
dc.contributor.authorReichmann, Nathalie T.
dc.contributor.authorPereira, Pedro M.
dc.contributor.authorRoemer, Terry
dc.contributor.authorFilipe, Sérgio R.
dc.contributor.authorPereira-Leal, José B.
dc.contributor.authorLigoxygakis, Petros
dc.contributor.authorPinho, Mariana G.
dc.date.accessioned2015-10-15T14:26:17Z
dc.date.available2015-10-15T14:26:17Z
dc.date.issued2015-05-07
dc.description.abstractMany important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus.pt_PT
dc.description.sponsorshipFCT grant: (PEst-OE/EQB/LA0004/2011), National Institute of General Medical Sciences grant: (GM85024), FCT fellowships: (SFRH/BPD/23812/2005, SFRH/BD/41119/2007, SFRH/BD/28440/2006), European Molecular Biology Organization long-term fellowship: (ALTF 782–2012).pt_PT
dc.identifier10.1371/journal.ppat.1004891
dc.identifier.citationReed P, Atilano ML, Alves R, Hoiczyk E, Sher X, Reichmann NT, et al. (2015) Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. PLoS Pathog 11(5): e1004891. doi:10.1371/journal.ppat.1004891pt_PT
dc.identifier.doi10.1371/journal.ppat.1004891
dc.identifier.urihttp://hdl.handle.net/10400.7/402
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relationThe cell wall synthetic machinery of Staphylococcus aureus and its response to the presence of antibiotics
dc.relationFinding New Mechanisms for Protein Localization in Bacteria
dc.relationTracking the synthesis of the Chlamydia cell wall - a biological paradox in intracellular and evasive bacteria
dc.relation.publisherversionhttp://www.plospathogens.org/article/Authors/info:doi/10.1371/journal.ppat.1004891pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectStaphylococcus aureuspt_PT
dc.subjectAntibiotic Resistancept_PT
dc.titleStaphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistancept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleThe cell wall synthetic machinery of Staphylococcus aureus and its response to the presence of antibiotics
oaire.awardTitleFinding New Mechanisms for Protein Localization in Bacteria
oaire.awardTitleTracking the synthesis of the Chlamydia cell wall - a biological paradox in intracellular and evasive bacteria
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-MIC%2F099151%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/310987/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-MIC%2F100747%2F2008/PT
oaire.citation.endPage19pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePlos Pathogenspt_PT
oaire.citation.volume11pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamFP7
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication45df7208-9576-4995-bb11-ff6eb2473f22
relation.isProjectOfPublication84d520c3-3f82-4c26-b9d0-7449d4d58dfc
relation.isProjectOfPublicationea86ab53-e4db-4ebd-802c-4d0e66434fbe
relation.isProjectOfPublication.latestForDiscovery84d520c3-3f82-4c26-b9d0-7449d4d58dfc

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