Heterogeneity in populations of enterohaemorrhagic Escherichia coli undergoing d -serine adaptation
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MINI-REVIEW
Heterogeneity in populations of enterohaemorrhagic Escherichia coli undergoing d‑serine adaptation Nicky O’Boyle1 · Andrew J. Roe1 Received: 15 October 2020 / Revised: 2 November 2020 / Accepted: 4 November 2020 © The Author(s) 2020
Abstract Phenotypic and genetic heterogeneities are conserved features of prokaryotic populations. During periods of stress, this programmed diversity increases the likelihood that variants within the population will survive the adverse conditions, allowing for proliferation. Phenotypic heterogeneity can have a mutational or indeed a non-mutational basis as observed in bet-hedging strategies adopted by antibiotic-tolerant persister cells. Genetic variants can arise by phase variation (slip-strand mispairing, promoter inversions etc.), nucleotide polymorphisms resulting from replication errors or larger rearrangements such as deletions and insertions. In the face of selective pressures, these alterations may be neutral, beneficial or deleterious. We recently described the genetic basis of tolerance to a normally toxic metabolite, d-serine (d-ser) in enterohaemorrhagic E. coli (EHEC). Here we summarize our work in the context of population dynamics, provide further discussion on the distinction between these tolerance mechanisms and the importance of heterogeneity for maximising adaptive potential. Keywords Adaptive evolution · EHEC · Mutation · Pathogenesis · Metabolism Enterohaemorrhagic E. coli displays significant growth arrest upon exposure to millimolar concentrations of d-ser and this is associated with activation of an unusual SOSlike response characterized by induction of RecA expression (Connolly and Roe 2016). Moreover, its primary colonization apparatus—the locus of enterocyte effacement (LEE)-encoded type 3 secretion system is transcriptionally repressed by D-ser (Connolly et al. 2015), further supporting the notion that EHEC has evolved to become particularly incompatible with exposure to this amino acid (Fig. 1a). In our recent work (O’Boyle et al. 2020), we examined the effect of repeated exposure of EHEC to physiological concentrations of d-ser that were able to inhibit growth, thereby promoting adaptive evolution and the development of tolerance to d-ser. Whole-genome sequencing (WGS) and
Communicated by M. Kupiec. * Nicky O’Boyle [email protected] * Andrew J. Roe [email protected] 1
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK
transcriptomics were then used to reveal the genetic basis of tolerance. Complete d-ser tolerance was obtained through two distinct adaptive strategies: either by “zipping the cell envelope shut (Fig. 1b)” (blocking cytoplasmic accumulation of D-ser via the disruption of inner membrane transporters) or “eating the poison (Fig. 1c)” (constitutive activation of a d-ser deaminase that was normally locked in a silent state) (Fig. 1). “Zipping the envelope shut” was achieved primarily through inactivating single nucleotide polymorphisms (SNPs) in the d-ser transpo
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