Staphylococcus aureus induces formation of tubular structures decorated with the autophagic protein LC3.

LÓPEZ DE ARMENTIA, M.M.; COLOMBO M.I.

Puerto Natales

Workshop; EMBO Workshop: Current advances in membrane trafficking: Implications for polarity and diseases.; 2014

EMBO

Staphylococcus aureus is a pathogen that causes serious infectious diseases eventually leading to septic and toxic shock. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. After S. aureus is phagocytosed resides in a phagosome containing the autophagic protein LC3.We have shown that the pore-forming toxin α-hemolysin (Hla) is the S. aureus?secreted factor responsible for the activation of the autophagic pathway. Autophagy defends the mammalian cytosol against bacterial invasion. However, it has been previously shown that this pathogen subverts the autophagy pathway. Recent results from our laboratory indicate that S. aureus at early times post-infection generates tubular dynamic structures marked with LC3 protein. We determined that these tubular structures correspond also to the endocytic pathway, as they recruited Rab7. Furthermore, we demonstrate that the formation of these filaments depends on the integrity of microtubules, as their elongation was inhibited by Nocodazole treatment. In the endo-lysosomal system, various small GTPases of the Rab family facilitate transport by recruitment of relevant motor proteins from the dynein and kinesin families. The Rab7-interacting lysosomal protein (RILP) is a cytosolic protein that can be recruited to membrane by Rab7 to regulate late endo-lysosomal traffic. Based on these data, we demonstrated that the motor protein Kinesin1 (Kif5B) and RILP protein are necessary for S. aureus-induced filaments elongation. When these tubular structures were inhibited we observed a marked decrease in S. aureus replication, suggesting these structures are necessary for an efficient bacterial replication.