Macrophage adaptation leads to parallel evolution of genetically diverse Escherichia coli small‐colony variants with increased fitness in vivo and antibiotic collateral sensitivity. (30th June 2016)

• Record Type: Journal Article
• Authors: Ramiro, Ricardo S.; Costa, Henrique; Gordo, Isabel
• Is Part Of: Evolutionary applications. Volume 9:Number 8(2016)
• Page Start: 994
• Page End: 1004
• Publication Date: 2016-06-30
• Subjects: antibiotic resistance -- collateral sensitivity -- experimental evolution -- macrophages -- mouse gut colonization -- small‐colony variants -- whole‐genome sequencing; Evolution (Biology) -- Periodicals; Genetics -- Periodicals; Natural selection -- Periodicals; Ecology -- Periodicals; 576.8
• DOI: 10.1111/eva.12397
• Languages: English
• ISSNs: 1752-4571

Abstract

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.