Phenotypic heterogeneity in persisters: a novel ‘hunker’ theory of persistence

Author:

Urbaniec J1,Xu Ye1,Hu Y2,Hingley-Wilson S1ORCID,McFadden J13ORCID

Affiliation:

1. Department of Microbial Sciences and University of Surrey, Guildford, Surrey, GU27XH, UK

2. Farnborough Sensonic limited, Farnborough road, GU14 7NA, UK

3. Quantum biology doctoral training centre, University of Surrey, Guildford, Surrey, GU27XH, UK

Abstract

ABSTRACT Persistence has been linked to treatment failure since its discovery over 70 years ago and understanding formation, nature and survival of this key antibiotic refractory subpopulation is crucial to enhancing treatment success and combatting the threat of antimicrobial resistance (AMR). The term ‘persistence’ is often used interchangeably with other terms such as tolerance or dormancy. In this review we focus on ‘antibiotic persistence’ which we broadly define as a feature of a subpopulation of bacterial cells that possesses the non-heritable character of surviving exposure to one or more antibiotics; and persisters as cells that possess this characteristic. We discuss novel molecular mechanisms involved in persister cell formation, as well as environmental factors which can contribute to increased antibiotic persistence in vivo, highlighting recent developments advanced by single-cell studies. We also aim to provide a comprehensive model of persistence, the ‘hunker’ theory which is grounded in intrinsic heterogeneity of bacterial populations and a myriad of ‘hunkering down’ mechanisms which can contribute to antibiotic survival of the persister subpopulation. Finally, we discuss antibiotic persistence as a ‘stepping-stone’ to AMR and stress the urgent need to develop effective anti-persister treatment regimes to treat this highly clinically relevant bacterial sub-population.

Funder

MRC

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology

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