Autophagy mediates tolerance to Staphylococcus aureus alpha-toxin

Cell Host Microbe. 2015 Apr 8;17(4):429-40. doi: 10.1016/j.chom.2015.03.001. Epub 2015 Mar 26.


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 (Atg16L1(HM)), 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, Atg16L1(HM) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Proteins
  • Bacterial Toxins / immunology*
  • Carrier Proteins / genetics
  • Hemolysin Proteins / immunology*
  • Immune Tolerance*
  • Methicillin-Resistant Staphylococcus aureus / immunology*
  • Mice, Knockout
  • Pneumonia, Staphylococcal / immunology
  • Pneumonia, Staphylococcal / microbiology
  • Sepsis / immunology
  • Sepsis / microbiology
  • Survival Analysis


  • Atg16l1 protein, mouse
  • Autophagy-Related Proteins
  • Bacterial Toxins
  • Carrier Proteins
  • Hemolysin Proteins
  • staphylococcal alpha-toxin