leukotoxin and Abscess

We 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.. MSSA 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.. 9% (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.. Our results suggest flucloxacillin in combination with a single protein-synthesis inhibitor such as clindamycin would give the best treatment outcome.

Topics: Abscess; Animals; Anti-Bacterial Agents; Bacterial Toxins; Blotting, Western; Clindamycin; Disease Models, Animal; Exotoxins; Female; Humans; Leukocidins; Mice, Inbred BALB C; Microbial Sensitivity Tests; Real-Time Polymerase Chain Reaction; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus

To determine the efficacy of leukotoxin-based Fusobacterium necrophorum vaccines and dietary tylosin in providing protection against experimentally induced hepatic abscesses in steers.. 30 steers assigned randomly to 6 treatment groups of 5 steers each: 1, phosphate-buffered saline solution (PBSS; control); 2, PBSS control, fed tylosin (100 mg/steer) daily; 3, inactivated whole-cell culture with oil emulsion adjuvant; 4, culture supernatant (crude toxoid) with oil emulsion adjuvant; 5, semipurified leukotoxoid with oil emulsion adjuvant; and 6, semipurified leukotoxoid with saponin adjuvant.. Steers were inoculated SC with emulsified antigen or PBSS on days 0 and 21. Blood samples were collected at weekly intervals to monitor serum antileukotoxin antibody titer. On day 42, all steers were challenge exposed intraportally with F necrophorum culture. Three weeks later (day 63), steers were euthanatized and necropsied to examine liver and assess protection.. Antileukotoxin antibody titers of all vaccinated groups markedly increased from baseline values, and mean titers of vaccinated groups were higher than those of the control and tylosin-treated groups. Steers vaccinated with culture supernatant with oil emulsion adjuvant or semipurified leukotoxoid with saponin adjuvant had the highest mean antibody titers. All 5 steers in the control group developed liver abscesses. Tylosin feeding did not protect steers challenge exposed with F necrophorum intraportally.. Culture supernatant was more protective than whole-cell culture or semipurified leukotoxin against experimentally induced hepatic abscesses. Partial purification of leukotoxin appeared to reduce its protective immunity.

Topics: Abscess; Adjuvants, Immunologic; Animal Feed; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Antibody Formation; Bacterial Toxins; Bacterial Vaccines; Cattle; Cattle Diseases; Exotoxins; Fusobacterium Infections; Fusobacterium necrophorum; Liver; Liver Diseases; Liver Function Tests; Male; Neutralization Tests; Orchiectomy; Tylosin; Vaccination