Edinburgh Napier University

  An editorial which frames the Research Topic's aims and objectives placing its findings in a broader context.

Staphylococcus aureus and coagulase-negative staphylococci are medically important pathogens known for a pronounced phenotypic variability associated with different modes of existence. Although phenotypic transition can be stochastic and perceived as a part of the bacterial life cycle, external pressures such as host-mediated stress also promote the formation of specific bacterial subpopulations characterized by different structural and physiological adaptations. Transition from a normal to a slow-growing or dormant phenotype is considered a bet-hedging strategy to increase the chance of bacterial survival under harsh conditions, thereby saving the population from extinction. Phenotype switching has been linked to persistence in host cells, treatment failure and the development of chronic and recurrent infections. Staphylococcal small colony variants (SCVs) and persister cells (PCs) are among the cell types raising the greatest scientific interest. Although each of these phenotypes is characterised by distinctive features, they can be tied by several common threads which include a quiescent metabolic state, tolerance to antimicrobial agents as well as evasion of the host immune defence mechanisms. Especially when shielded from the immune system, as is the case in biofilms or inside host cells, SCVs and PCs are difficult to eradicate despite prolonged antibiotic treatment. These subpopulations are characterized by variable stability and can revert to rapidly growing cell types (SCVs) or exit dormancy and resume growth (PCs).

This Research Topic contributes to the latest advances in the field of phenotypic heterogeneity and its relation to the pathogenesis of staphylococcal infections. We address novel issues related to mechanisms contributing to the formation and maintenance of bacterial subpopulations with emphasis on their role during infection. Recent findings have undermined the original definition of PCs as dormant and indicate that they are not completely devoid of metabolic activity. Major molecular reprogramming as well as an interplay between multiple metabolic processes have been suggested to be required for the persister phenotype. Profound conversion of the microorganism’s metabolism resulting from mutations and/or originating from regulatory mechanisms has been reported for SCVs and new postulates regarding the mechanisms explaining the increased emergence of SCV selection are being published. Concepts of interest also include phenotypes related to dormancy such as the viable but non-culturable (VBNC) variants in which cells remain viable but are unable to resume growth on normally permissive media unless specifically stimulated. Unravelling mechanisms underlying the existence of phenotypic variants can set the foundations of novel treatment strategies against infections associated with alternative bacterial cell types.