Abstract
Staphylococcus aureus can undergo phenotypic switching between a normal colony phenotype (NCP) and a small colony variant (SCV). The SCV phenotype confers increased antibiotic resistance and the capacity to persist within human tissues and cells, and because these cells can revert back to the NCP they cause chronic and/or recurrent infections that are very difficult to treat. A complete picture of the genetic events that can lead to phenotypic switching in S. aureus is currently lacking. We describe the selection of an SCV with a previously unreported genetic alteration leading to an ochre mutation of aroD. In addition to the known mechanisms of phenotypic switching between the SCV and the NCP we describe a previously unreported mechanism involving tRNA ochre suppressors arising. The ochre suppressor strains had wild-type growth rates and restored antibiotic sensitivity, similar to the wild-type strain. However, whilst they had increased virulence compared to the SCV parent strain, their virulence was not restored to that of the NCP parental strain. These findings establish that phenotypic switching between the NCP and SCV states can give rise to strains with different pathogenic potential.
Highlights
Staphylococcus aureus small colony variants (SCVs) are a naturally arising slow-growing subpopulation of S. aureus
Studies on S. aureus SCVs have focused on hemin or menadione auxotrophs, mainly using stable defined hemB and menD
S. aureus SCVs are frequently isolated from patients, but the genetic basis of SCV phenotypes is not often characterized (Kahl et al, 2003; Yagci et al, 2013)
Summary
Staphylococcus aureus small colony variants (SCVs) are a naturally arising slow-growing subpopulation of S. aureus. S. aureus SCVs are frequently associated with persistent and recurrent infections, such as osteomyelitis, implant infections and airway infections in cystic fibrosis patients (von Eiff et al, 2006), or patients receiving long-term antibiotic treatment (Proctor et al, 1995; von Eiff et al, 1997a, 2001). This is in part because SCVs can persist within non-phagocytic host cells such as epithelial cells (Atalla et al, 2010), endothelial cells (von Eiff et al, 1997b) and bone cells (Wright and Nair, 2010). In addition genes responsible for adhesion and biofilm formation are generally upregulated in SCVs (Proctor et al, 2006), enhancing the capacity of the bacterium to persist in implant infections, cystic fibrosis patients, and osteomyelitis
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