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Targeting Staphylococcus aureus ?-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections.

ABSTRACT: Staphyococcus aureus frequently causes recurrent skin and soft-tissue infection (SSTI). In the pediatric population, elevated serum antibody targeting S. aureus ?-toxin is correlated with a reduced incidence of recurrent SSTI. Using a novel model of recurrent SSTI, we demonstrated that expression of ?-toxin during primary infection increases the severity of recurrent disease. Antagonism of ?-toxin by either a dominant-negative toxin mutant or a small molecule inhibitor of the toxin receptor ADAM10 during primary infection reduces reinfection abscess severity. Early neutralization of ?-toxin activity during S. aureus SSTI therefore offers a new therapeutic strategy to mitigate primary and recurrent disease.

SUBMITTER: Sampedro GR

PROVIDER: S-EPMC4207862 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Targeting Staphylococcus aureus α-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections.

Sampedro Georgia R GR DeDent Andrea C AC Becker Russell E N RE Berube Bryan J BJ Gebhardt Michael J MJ Cao Hongyuan H Bubeck Wardenburg Juliane J

The Journal of infectious diseases 20140416 7

Staphyococcus aureus frequently causes recurrent skin and soft-tissue infection (SSTI). In the pediatric population, elevated serum antibody targeting S. aureus α-toxin is correlated with a reduced incidence of recurrent SSTI. Using a novel model of recurrent SSTI, we demonstrated that expression of α-toxin during primary infection increases the severity of recurrent disease. Antagonism of α-toxin by either a dominant-negative toxin mutant or a small molecule inhibitor of the toxin receptor ADAM ...[more]

PMID: 24740631

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Project description:BackgroundStaphylococcus aureus is one predominant cause of skin and soft-tissue infections (SSTIs), but little information exists regarding the characterization of S. aureus from non-native patients with SSTIs in China.MethodsIn this study, we enrolled 52 non-native patients with S. aureus SSTIs, and 65 native control patients with S. aureus SSTIs in Shanghai. 52 and 65 S. aureus isolates were collected from both groups, respectively. S. aureus isolates were characterized by antimicrobial susceptibility testing, toxin gene detection, and molecular typing with sequence type, spa type, agr group and SCCmec type.ResultsMethicillin-resistant S. aureus (MRSA) was detected in 8 non-native patients and 14 native patients with SSTIs. Overall, antimicrobial susceptibilities of S. aureus isolated from non-native patients were found higher than those from native patients. CC59 (ST338 and ST59) was found in a total of 14 isolates (4 from non-native patients; 10 from native patients), 9 of which were carrying lukS/F-PV (3 from non-native patients; 6 from native patients). ST7 was found in 12 isolates and all 12 isolates were found in native patients. The livestock-associated clone ST398 was found in 11 isolates (6 from non-native patients; 5 from native patients), and 5 ST398 lukS/F-PV-positive methicillin-susceptible S. aureus (MSSA) were all discovered among non-native patients. The molecular epidemiology of S. aureus isolated from non-native patients was quite different from those from native patients. lukS/F-PV was more frequent in isolates originating from non-native patients with SSTIs compared to native patients (31 vs. 7, P <0.0001).ConclusionsCC59 was the most common clonal complex among patients with SSTIs in Shanghai. The other most common sequence types were ST7 and Livestock ST398. The molecular epidemiology of S. aureus isolated from non-native patients was quite different from those from native patients. S. aureus isolated from non-native patients was more likely to carry lukS/F-PV.

Dataset Information

Targeting Staphylococcus aureus ?-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections.

Publications

Targeting Staphylococcus aureus α-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections.

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