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Enhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophages

2016-09Journal article Open access
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dc.contributor.authorDurão, Paulo
dc.contributor.authorGülereşi, Daniela
dc.contributor.authorProença, João
dc.contributor.authorGordo, Isabel
dc.date.accessioned2018-05-18T12:00:05Z
dc.date.available2018-05-18T12:00:05Z
dc.date.issued2016-09
dc.descriptionThe deposited article is a post-print version and has been submitted to peer review.pt_PT
dc.descriptionThis deposit is composed by the main article plus the supplementary materials of the publication.pt_PT
dc.description.abstractThe evolution of multiple-antibiotic-resistant bacteria is an increasing global problem. Even though mutations causing resistance usually incur a fitness cost in the absence of antibiotics, the magnitude of such costs varies across environments and genomic backgrounds. We studied how the combination of mutations that confer resistance to rifampin (Rif(r)) and streptomycin (Str(r)) affects the fitness of Escherichia coli when it interacts with cells from the immune system, i.e., macrophages (Mϕs). We found that 13 Rif(r) Str(r) doubly resistant genotypes, of the 16 tested, show a survival advantage inside Mϕs, indicating that double resistance can be highly beneficial in this environment. Our results suggest that there are multiple paths to acquire multiple-drug resistance in this context, i.e., if a clone carrying Rif(r) allele H526 or S531 acquires a second mutation conferring Str(r), the resulting double mutant has a high probability of showing increased survival inside Mϕs. On the other hand, we found two cases of sign epistasis between mutations, leading to a significant decrease in bacterial survival. Remarkably, infection of Mϕs with one of these combinations, K88R+H526Y, resulted in an altered pattern of gene expression in the infected Mϕs. This indicates that the fitness effects of resistance may depend on the pattern of gene expression of infected host cells. Notwithstanding the benefits of resistance found inside Mϕs, the Rif(r) Str(r) mutants have massive fitness costs when the bacteria divide outside Mϕs, indicating that the maintenance of double resistance may depend on the time spent within and outside phagocytic cells.pt_PT
dc.description.sponsorshipThis study received funding from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement 260421-ECOADAPT. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationDurão P, Güleres¸i D, Proença J, Gordo I. 2016. Enhanced survival of rifampin- and streptomycin-resistant Escherichia coli inside macrophages. Antimicrob Agents Chemother 60:4324 –4332. doi:10.1128/AAC.00624-16.pt_PT
dc.identifier.doi10.1128/AAC.00624-16pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/871
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationMicrobial adaptation within ecosystems
dc.relation.publisherversionhttp://aac.asm.org/content/60/7/4324.longpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAnimalspt_PT
dc.subjectAnti-Bacterial Agentspt_PT
dc.subjectDrug Resistance, Bacterialpt_PT
dc.subjectDrug Resistance, Multiple, Bacterialpt_PT
dc.subjectEscherichia colipt_PT
dc.subjectMacrophagespt_PT
dc.subjectMicept_PT
dc.subjectRAW 264.7 Cellspt_PT
dc.subjectReal-Time Polymerase Chain Reactionpt_PT
dc.subjectReverse Transcriptase Polymerase Chain Reactionpt_PT
dc.subjectRifampinpt_PT
dc.subjectStreptomycinpt_PT
dc.titleEnhanced Survival of Rifampin- and Streptomycin-Resistant Escherichia coli Inside Macrophagespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMicrobial adaptation within ecosystems
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/260421/EU
oaire.citation.endPage4332pt_PT
oaire.citation.issue7pt_PT
oaire.citation.startPage4324pt_PT
oaire.citation.titleAntimicrobial Agents and Chemotherapypt_PT
oaire.citation.volume60pt_PT
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication1f01df05-f8af-4e76-8dec-0fc6237b41fd
relation.isProjectOfPublication.latestForDiscovery1f01df05-f8af-4e76-8dec-0fc6237b41fd

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