dc.contributor.author	Ramiro, Ricardo S.
dc.contributor.author	Costa, Henrique
dc.contributor.author	Gordo, Isabel
dc.date.accessioned	2016-10-17T16:19:26Z
dc.date.available	2016-10-17T16:19:26Z
dc.date.issued	2016-06-30
dc.description.abstract	Small-colony variants (SCVs) are commonly observed in evolution experiments and clinical isolates, being associated with antibiotic resistance and persistent infections. We recently observed the repeated emergence of Escherichia coli SCVs during adaptation to the interaction with macrophages. To identify the genetic targets underlying the emergence of this clinically relevant morphotype, we performed whole-genome sequencing of independently evolved SCV clones. We uncovered novel mutational targets, not previously associated with SCVs (e.g. cydA, pepP) and observed widespread functional parallelism. All SCV clones had mutations in genes related to the electron-transport chain. As SCVs emerged during adaptation to macrophages, and often show increased antibiotic resistance, we measured SCV fitness inside macrophages and measured their antibiotic resistance profiles. SCVs had a fitness advantage inside macrophages and showed increased aminoglycoside resistance in vitro, but had collateral sensitivity to other antibiotics (e.g. tetracycline). Importantly, we observed similar results in vivo. SCVs had a fitness advantage upon colonization of the mouse gut, which could be tuned by antibiotic treatment: kanamycin (aminoglycoside) increased SCV fitness, but tetracycline strongly reduced it. Our results highlight the power of using experimental evolution as the basis for identifying the causes and consequences of adaptation during host-microbe interactions.	pt_PT
dc.description.sponsorship	European Research Council under the European Community’ Seventh Framework Programme grant:(FP7/2007-2013); German Science Foundation grants: (G-410861, SFB-680); EMMA; InfrafrontierI3.	pt_PT
dc.identifier.citation	Ramiro, R. S., Costa, H. and Gordo, I. (2016), Macrophage adaptation leads to parallel evolution of genetically diverse Escherichia coli small-colony variants with increased fitness in vivo and antibiotic collateral sensitivity. Evol Appl, 9: 994–1004. doi:10.1111/eva.12397	pt_PT
dc.identifier.doi	10.1111/eva.12397	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.7/701
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Wiley	pt_PT
dc.relation	Microbial adaptation within ecosystems
dc.relation	Adaptation of commensal bacteria to the mammalian gut
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	antibiotic resistance	pt_PT
dc.subject	collateral sensitivity	pt_PT
dc.subject	experimental evolution	pt_PT
dc.subject	macrophages	pt_PT
dc.subject	mouse gut colonization	pt_PT
dc.subject	small‐colony variants	pt_PT
dc.subject	whole‐genome sequencing	pt_PT
dc.title	Macrophage adaptation leads to parallel evolution of genetically diverseEscherichia colismall-colony variants with increased fitness in vivo and antibiotic collateral sensitivity	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.awardTitle	Microbial adaptation within ecosystems
oaire.awardTitle	Adaptation of commensal bacteria to the mammalian gut
oaire.awardURI	info:eu-repo/grantAgreement/EC/FP7/260421/EU
oaire.awardURI	info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-EVF%2F118075%2F2010/PT
oaire.awardURI	info:eu-repo/grantAgreement/FCT/3599-PPCDT/RECI%2FIMI-IMU%2F0038%2F2012/PT
oaire.citation.endPage	1004	pt_PT
oaire.citation.issue	8	pt_PT
oaire.citation.startPage	994	pt_PT
oaire.citation.title	Evolutionary Applications	pt_PT
oaire.citation.volume	9	pt_PT
oaire.fundingStream	FP7
oaire.fundingStream	3599-PPCDT
oaire.fundingStream	3599-PPCDT
project.funder.identifier	http://doi.org/10.13039/501100008530
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.name	European Commission
project.funder.name	Fundação para a Ciência e a Tecnologia
project.funder.name	Fundação para a Ciência e a Tecnologia
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
relation.isProjectOfPublication	1f01df05-f8af-4e76-8dec-0fc6237b41fd
relation.isProjectOfPublication	8a096e46-5521-429a-b9e8-8a7901fe8b30
relation.isProjectOfPublication	1470c3e4-1d23-40cc-9500-9f8843b0e35d
relation.isProjectOfPublication.latestForDiscovery	1f01df05-f8af-4e76-8dec-0fc6237b41fd

Macrophage adaptation leads to parallel evolution of genetically diverseEscherichia colismall-colony variants with increased fitness in vivo and antibiotic collateral sensitivity

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