IngentaConnect Derepression of Salmonella pathogenicity island 1 genes within ma...

Authors: Akiko Takaya¹; Akiko Suzuki¹; Yuji Kikuchi²; Masahiro Eguchi²; Emiko Isogai³; Toshifumi Tomoyasu¹; Tomoko Yamamoto¹

Source: Cellular Microbiology, Volume 7, Number 1, January 2005 , pp. 79-90(12)

Publisher: Blackwell Publishing

Abstract:

Summary

Salmonella enterica serovar Typhimurium has been reported to induce apoptosis in infected macrophages within 14 h from the time of infection by a caspase-1-dependent mechanism. Here, we demonstrate that depletion of Lon protease in serovar Typhimurium induces rapid and massive apoptosis in macrophages by a mechanism involving both caspases-1 and -3. This excessive induction of apoptosis was abrogated by disruption of invF, which is required for the expression of the Salmonella pathogenicity island 1 (SPI1) genes. Expression of hilA, a central regulator of SPI1 transcription, was repressed in the macrophages after phagocytosis, but this gene was continuously expressed when the Delta

Lon mutant grew within the macrophages, so the SPI1 proteins accumulated. Thus, the increase in macrophage apoptosis induced by the Delta

Lon mutant could result from continued expression of SPI1 genes under conditions where they are normally repressed. Once Salmonella has established a systemic infection, excess apoptosis of macrophages cells upon which the organism is reliant would be detrimental to the pathogen. Therefore, the Lon protease may be required to suppress apoptosis sufficiently to allow time for the bacterium to replicate, escape and invade new macrophages.

Document Type: Research article

DOI: 10.1111/j.1462-5822.2004.00435.x

Affiliations: 1: Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 263-8522, Japan. 2: Department of Infection Control and Immunology, Kitasato Institute for Life Sciences, Kitasato University, Tokyo, 108-8641, Japan. 3: Department of Preventive Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.

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Derepression of Salmonella pathogenicity island 1 genes within macrophages leads to rapid apoptosis via caspase-1- and caspase-3-dependent pathways