The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages

Miskinyte, Migla; Sousa, Ana; Ramiro, Ricardo S.; de Sousa, Jorge A. Moura; Kotlinowski, Jerzy; Caramalho, Iris; Magalhães, Sara; Soares, Miguel P.; Gordo, Isabel

Publication

The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages

2013-11-12Journal article

dc.contributor.author	Miskinyte, Migla
dc.contributor.author	Sousa, Ana
dc.contributor.author	Ramiro, Ricardo S.
dc.contributor.author	de Sousa, Jorge A. Moura
dc.contributor.author	Kotlinowski, Jerzy
dc.contributor.author	Caramalho, Iris
dc.contributor.author	Magalhães, Sara
dc.contributor.author	Soares, Miguel P.
dc.contributor.author	Gordo, Isabel
dc.date.accessioned	2015-11-03T19:00:53Z
dc.date.available	2015-11-03T19:00:53Z
dc.date.issued	2013-11-12
dc.description.abstract	Antagonistic interactions are likely important driving forces of the evolutionary process underlying bacterial genome complexity and diversity. We hypothesized that the ability of evolved bacteria to escape specific components of host innate immunity, such as phagocytosis and killing by macrophages (MΦ), is a critical trait relevant in the acquisition of bacterial virulence. Here, we used a combination of experimental evolution, phenotypic characterization, genome sequencing and mathematical modeling to address how fast, and through how many adaptive steps, a commensal Escherichia coli (E. coli) acquire this virulence trait. We show that when maintained in vitro under the selective pressure of host MΦ commensal E. coli can evolve, in less than 500 generations, virulent clones that escape phagocytosis and MΦ killing in vitro, while increasing their pathogenicity in vivo, as assessed in mice. This pathoadaptive process is driven by a mechanism involving the insertion of a single transposable element into the promoter region of the E. coli yrfF gene. Moreover, transposition of the IS186 element into the promoter of Lon gene, encoding an ATP-dependent serine protease, is likely to accelerate this pathoadaptive process. Competition between clones carrying distinct beneficial mutations dominates the dynamics of the pathoadaptive process, as suggested from a mathematical model, which reproduces the observed experimental dynamics of E. coli evolution towards virulence. In conclusion, we reveal a molecular mechanism explaining how a specific component of host innate immunity can modulate microbial evolution towards pathogenicity.	pt_PT
dc.description.sponsorship	LAO/ITQB, FCT	pt_PT
dc.identifier	10.1371/journal.ppat.1003802
dc.identifier.citation	Miskinyte M, Sousa A, Ramiro RS, de Sousa JAM, Kotlinowski J, et al. (2013) The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages. PLoS Pathog 9(12): e1003802. doi:10.1371/journal.ppat.1003802	pt_PT
dc.identifier.doi	10.1371/journal.ppat.1003802
dc.identifier.uri	http://hdl.handle.net/10400.7/465
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Public Library of Science	pt_PT
dc.relation	Microbial adaptation within ecosystems
dc.relation.publisherversion	http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003802	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	Adaptation, Biological	pt_PT
dc.subject	Escherichia coli	pt_PT
dc.subject	Genetic Variation	pt_PT
dc.subject	Macrophages	pt_PT
dc.title	The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.awardTitle	Microbial adaptation within ecosystems
oaire.awardURI	info:eu-repo/grantAgreement/EC/FP7/260421/EU
oaire.citation.endPage	15	pt_PT
oaire.citation.issue	12	pt_PT
oaire.citation.startPage	1	pt_PT
oaire.citation.title	Plos Pathogens	pt_PT
oaire.citation.volume	9	pt_PT
oaire.fundingStream	FP7
project.funder.identifier	http://doi.org/10.13039/501100008530
project.funder.name	European Commission
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
relation.isProjectOfPublication	1f01df05-f8af-4e76-8dec-0fc6237b41fd
relation.isProjectOfPublication.latestForDiscovery	1f01df05-f8af-4e76-8dec-0fc6237b41fd