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Antibiotic treatment selects for cooperative virulence of Salmonella typhimurium.
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2014 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 24, no 17Article in journal (Refereed) Published
Abstract [en]

Antibiotics are powerful therapeutics but are not equally effective against all cells in bacterial populations. Bacteria that express an antibiotic-tolerant phenotype ("persisters") can evade treatment [1]. Persisters can cause relapses of the infection after the end of the therapy [2]. It is still poorly understood whether persistence affects the evolution of bacterial virulence. During infections, persisters have been found preferentially at particular sites within the host [3, 4]. If bacterial virulence factors are required to reach such sites, treatment with antibiotics could impose selection on the expression of virulence genes, in addition to their well-established effects on bacterial resistance. Here, we report that treatment with antibiotics selects for virulence and fosters transmissibility of Salmonella Typhimurium. In a mouse model for Salmonella diarrhea, treatment with the broad-spectrum antibiotic ciprofloxacin reverses the outcome of competition between wild-type bacteria and avirulent mutants that can spontaneously arise during within-host evolution [5]. While avirulent mutants take over the gut lumen and abolish disease transmission in untreated mice, ciprofloxacin tilts the balance in favor of virulent, wild-type bacteria. This is explained by the need for virulence factors to invade gut tissues and form a persistent reservoir. Avirulent mutants remain in the gut lumen and are eradicated. Upon cessation of antibiotic treatment, tissue-lodged wild-type pathogens reseed the gut lumen and thereby facilitate disease transmissibility to new hosts. Our results suggest a general principle by which antibiotic treatment can promote cooperative virulence during within-host evolution, increase duration of transmissibility, and thereby enhance the spread of an infectious disease.

Place, publisher, year, edition, pages
2014. Vol. 24, no 17
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-309866DOI: 10.1016/j.cub.2014.07.028PubMedID: 25131673OAI: oai:DiVA.org:uu-309866DiVA: diva2:1053048
Available from: 2016-12-08 Created: 2016-12-08 Last updated: 2017-11-29

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