pH Sensing by Intracellular Salmonella Induces Effector Translocation

• Published in: Science (American Association for the Advancement of Science) 2010-05, Vol.328 (5981), p.1040-1043
• Main Authors: Yu, Xiu-Jun, McGourty, Kieran, Liu, Mei, Unsworth, Kate E, Holden, David W
• Format: Article
• Language: English
• Subjects: Bacteria; Bacterial Physiological Phenomena; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Cell membranes; Cytosol - chemistry; Epithelial cells; Fundamental and applied biological sciences. Psychology; Genomic Islands; HeLa Cells; Humans; Hydrogen-Ion Concentration; Immunoblotting; Microbiology; Molecular Chaperones - metabolism; Multiprotein Complexes - metabolism; Mutation; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Plasmids; Proteins; Salmonella; Salmonella enterica; Salmonella typhimurium - genetics; Salmonella typhimurium - growth & development; Salmonella typhimurium - metabolism; Salmonella typhimurium - pathogenicity; Secretion; Vacuoles - metabolism; Vacuoles - microbiology; Virulence Factors - metabolism
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1189000

Salmonella enterica is an important intracellular bacterial pathogen of humans and animals. It replicates within host-cell vacuoles by delivering virulence (effector) proteins through a vacuolar membrane pore made by the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (T3SS). T3SS assembly follows vacuole acidification, but when bacteria are grown at low pH, effector secretion is negligible. We found that effector secretion was activated at low pH from mutant strains lacking a complex of SPI-2-encoded proteins SsaM, SpiC, and SsaL. Exposure of wild-type bacteria to pH 7.2 after growth at pH 5.0 caused dissociation and degradation of SsaM/SpiC/SsaL complexes and effector secretion. In infected cells, loss of the pH 7.2 signal through acidification of host-cell cytosol prevented complex degradation and effector translocation. Thus, intravacuolar Salmonella senses host cytosolic pH, resulting in the degradation of regulatory complex proteins and effector translocation.