Staphylococcus aureus natural infection model uncovers how toxins contribute to disease

Staphylococcus aureus is the most common pathogen found in skin and soft tissue infections (SSTIs). One particular antibiotic-resistant strain of S. aureus accounts for many, if not most, cases of SSTIs across the U.S., Latin America and the Western Pacific. This strain makes a toxin associated with SSTIs, but the human-specific activity of the toxin makes animal models of disease incompatible. The lack of an appropriate model system to study human-specific S. aureus proteins has hampered understanding and slowed the creation of better therapies and vaccines for this bacterium. To better understand the virulence factors that contribute to S. aureus SSTIs, a study led by Victor Torres, PhD, St. Jude Department of Host-Microbe Interactions chair, used a rodent strain of S. aureus to study infection in a mouse, the strain’s natural host, rather than using human strains artificially adapted to mice. The researchers uncovered the toxin LukMF’ as the primary driver of pathogenesis by the rodent strain, including how it kills neutrophils to increase bacterial survival and related pathology. As LukMF’ is comparable to the human-specific toxin thought to drive SSTI pathogenesis in humans, this study gives insight into how these virulence mechanisms may be addressable in humans. The findings were published in Science Advances.

“Modelling infections in animals has been challenging as many human pathogens produce proteins that selectively target humans,” Torres said. “This host specificity has hampered our ability to identify the key host–pathogen interactions that need to be targeted for novel therapeutics. This new work highlights the power of studying infection in a natural setting, which we hope to capitalize on at St. Jude to advance the development of lifesaving novel anti-S. aureus therapeutics.”

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