The Autophagy Protein Atg16L1 and Staphylococcus aureus Pathogenesis

Staphylococcus aureus is a gram-positive pathogen that is a major cause of morbidity and mortality in humans, causing diseases such as sepsis, endocarditis, and pneumonia. Rapidly emerging antibiotic resistant strains pose a significant threat to human health; moreover, while many bacterial toxins have been identified, the host factors that contribute to pathogenesis of S. aureus are largely undefined. Components of the autophagy pathway have been shown to be crucial for controlling invading microorganisms during infection, and microbes have also evolved mechanisms to subvert the autophagic machinery for their own survival. Although, the role of autophagy has been shown to contribute to the intracellular life-cycle of S. aureus in vitro, the role of autophagy during in vivo infection has not been investigated. We have found that mice deficient in the essential autophagy gene Atg16L1 are highly susceptible to lethality following systemic infection by methicillin-resistant Staphylococcus aureus (MRSA). Mice deficient in LC3b are similarly susceptible to MRSA suggesting that this function of Atg16L1 is related to autophagy. Remarkably, this increase in lethality was not accompanied by an increase in bacterial burden. Rather, autophagy was necessary to prevent pathologies downstream of a bacterially encoded toxin. Our results suggest a previously unrecognized role for autophagy proteins in protection from MRSA infection and toxin-mediated damage, a ubiquitous virulence strategy utilized by human pathogens.