Autophagy mediates tolerance to staphylococcus aureus alpha-toxin

Katie Maurer, Tamara Reyes-Robles, Francis Alonzo, Joan Durbin, Victor J. Torres, Ken Cadwell

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Resistance and tolerance are two defense strategies employed by the host against microbial threats. Autophagy-mediated degradation of bacteria has been extensively described as a major resistance mechanism. Here we find that the dominant function of autophagy proteins during infections with the epidemic community-associated methicillin-resistant Staphylococcus aureus USA300 is to mediate tolerance rather than resistance. Atg16L1 hypomorphic mice (Atg16L1HM), which have reduced autophagy, were highly susceptible to lethality in both sepsis and pneumonia models of USA300 infection. Autophagy confers protection by limiting the damage caused by α-toxin, particularly to endothelial cells. Remarkably, Atg16L1HM mice display enhanced survival rather than susceptibility upon infection with α-toxin-deficient S. aureus. These results identify an essential role for autophagy in tolerance to Staphylococcal disease and highlight how a single virulence factor encoded by a pathogen can determine whether a given host factor promotes tolerance or resistance.

Original languageEnglish (US)
Pages (from-to)429-440
Number of pages12
JournalCell Host and Microbe
Volume17
Issue number4
DOIs
StatePublished - Apr 8 2015

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

Fingerprint

Dive into the research topics of 'Autophagy mediates tolerance to staphylococcus aureus alpha-toxin'. Together they form a unique fingerprint.

Cite this