Abstract
SummaryObjectivesWe set out to investigate the impact of common antibiotics on Panton–Valentine Leucocidin (PVL) expression by methicillin-sensitive Staphylococcus aureus (MSSA). PVL expression by methicillin-resistant S. aureus (MRSA) is reportedly enhanced by β-lactams, but inhibited by protein-synthesis inhibitors, a fact that has influenced management of infections associated with PVL. Although PVL is more frequently associated with MSSA than MRSA in the UK, the effect of antibiotics on PVL expression by MSSA has not been fully addressed.MethodsMSSA was cultured in vitro with varying concentrations of flucloxacillin, clindamycin or linezolid and PVL expression measured by qRT-PCR and Western blotting. A murine MSSA abscess model was developed to measure leucocidin expression in vivo following antibiotic treatment.Results9% (27/314) of MSSA isolates from patients with uncomplicated community skin/soft tissue infections were positive for PVL genes (lukFS-PV). PVL expression by MSSA in broth was unaffected by varying concentrations of flucloxacillin, clindamycin or linezolid. In a murine abscess model, treatment with flucloxacillin did, however, enhance in vivo MSSA lukF-PV transcription and this was sustained even when flucloxacillin was combined with clindamycin, or clindamycin plus linezolid. Notwithstanding increased leucocidin transcription, functional leucotoxin activity was not enhanced. Treatment with flucloxacillin plus clindamycin significantly decreased leucotoxin activity, but the addition of a second protein synthesis inhibitor, linezolid, did not confer benefit.ConclusionsOur results suggest flucloxacillin in combination with a single protein-synthesis inhibitor such as clindamycin would give the best treatment outcome.
Highlights
Staphylococcus aureus is a globally important human pathogen that can cause a wide spectrum of diseases attributable to the range of virulence factors it is able to express
In north America and spreading globally, PantoneValentine Leucocidin (PVL) has been mainly associated with strains of community acquired methicillin resistant S. aureus (CA-methicillin-resistant S. aureus (MRSA))[3,4] but UK based studies suggest a more common association with community acquired methicillin sensitive S. aureus (MSSA) strains.[5]
In this work we aimed to explore the effect of the commonly used b-lactam flucloxacillin and two protein synthesis inhibitors, clindamycin and linezolid, on MSSA expression of PVL and other leucocidins
Summary
Staphylococcus aureus is a globally important human pathogen that can cause a wide spectrum of diseases attributable to the range of virulence factors it is able to express. PantoneValentine Leucocidin (PVL) is one of four pore forming bi-component toxins that may be expressed by S. aureus strains. The two co-transcribed components of PVL, LukS-PV and LukF-PV, when combined can lyse human cells expressing C5a receptors, including neutrophils.[1] Strains carrying PVL typically cause suppurative skin and soft tissue infections and severe necrotising pneumonia.[2] In north America and spreading globally, PVL has been mainly associated with strains of community acquired methicillin resistant S. aureus (CA-MRSA)[3,4] but UK based studies suggest a more common association with community acquired methicillin sensitive S. aureus (MSSA) strains.[5]
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