A8: Hypoxia shapes Salmonella virulence
A8: Hypoxia shapes Salmonella virulence
Low oxygen (O2) tension is a signature environmental cue of host tissues sensed by bacterial pathogens like Salmonella enterica serovar Typhimurium (S. Typhimurium). Hypoxia is integrated together with other signals present in the intestinal tract such as microbiota-derived short-chain fatty acids (SCFAs) and acidic pH, to regulate virulence functions in a precise spatio-temporal manner. Salmonella is particularly exposed to drastic environmental changes when approaching host cells. There is a zone of relative oxygenation due to oxygen diffusion from arterial blood and acidic pH gets neutralized by mucins overlaying the surface of enterocytes. Under conditions mimicking these changes, we found increased activity of the Salmonella Pathogenicity Island 1 encoded Type 3 Secretion System (T3SS-1) leading to elevated bacterial invasion. Here, hypoxia-dependent incapacitation of the repressor HilE enhanced the activity of the T3SS-1 master regulator HilD.
In the next funding period, we want to characterize these adaptation processes on the levels of transcription, post-translational modification and population heterogeneity using sophisticated infection models. A detailed knowledge of these mechanisms would significantly expand our knowledge how Salmonella recognizes host cells and might lead to the identification of novel targets for anti-infective therapies.
Supervisors
Dr. rer. nat. Roman Gerlach
91054 Erlangen
- Phone number: +49 9131 85-35991
- Email: roman.gerlach@uk-erlangen.de
