Haem toxicity provides a competitive advantage to the clinically relevant Staphylococcus aureus small colony variant phenotype.

Brittany E Herrin,Catherine A Wakeman,Shariful Islam,Stephanie P Kopanski,Lauren H Pert,Kaitlin N Rentschler

doi:10.1099/mic.0.001044

Brittany E Herrin, Catherine A Wakeman + Show 4 more

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https://doi.org/10.1099/mic.0.001044

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Abstract

Microorganisms encounter toxicities inside the host. Many pathogens exist as subpopulations to maximize survivability. Subpopulations of Staphylococcus aureus include antibiotic-tolerant small colony variants (SCVs). These mutants often emerge following antibiotic treatment but can be present in infections prior to antibiotic exposure. We hypothesize that haem toxicity in the host selects for respiration-deficient S. aureus SCVs in the absence of antibiotics. We demonstrate that some but not all respiration-deficient SCV phenotypes are more protective than the haem detoxification system against transient haem exposure, indicating that haem toxicity in the host may contribute to the dominance of menaquinone-deficient and haem-deficient SCVs prior to antibiotic treatment.

Highlights

Staphylococcus aureus is a common human commensal, infecting approximately one-third of the human population, primarily colonizing the nasopharynx [1]
It has been previously demonstrated that the small colony variants (SCVs) phenotype can be enriched by exposure to antimicrobials produced by Pseudomonas aeruginosa, host-derived antimicrobial peptides or aminoglycoside antibiotics [11,12,13,14]
The data presented demonstrate that the clinically relevant menaquinone-deficient SCV experiences a competitive advantage over respiring S. aureus when exposed to transient haem toxicity representative of conditions which may be experienced upon entry into the bloodstream prior to dissemination to sites of infection

Summary

Introduction

Staphylococcus aureus is a common human commensal, infecting approximately one-third of the human population, primarily colonizing the nasopharynx [1]. S. aureus adopts several mechanisms to survive and persist in the host environment in response to these pressures One such adaptation is the small colony variant (SCV) subpopulation [2,3,4]. The SCV of S. aureus has several phenotypic differences from its wild-type (WT) counterparts, such as slow growth rate, lack of carotenoid pigmentation and reduced haemolysis [5]. These traits result in suppression of several virulence factors, yet this phenotype is often observed in chronic infections, such as cystic fibrosis and osteomyelitis [6,7,8]. Both osteomyelitis and device-related infections often are associated with microbial dissemination through the bloodstream [17]

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