Urei is the link between intra-bacterial urease of Helicobacter pylori and gastric survival

Abstract

Despite the available genome sequence, the pathogenesis of gastroduodenal disease associated with the Gram negative, microaerophilic bacterium H pylori remains poorly understood. The full arsenal of weapons which H pylori utilizes during its infective stages to colonize and survive in the hostile environment of the stomach remains unclear, but of those identified (flagella, urease, adhesins, the cytotoxin VacA, the immunodominant antigen CagA, and the outer membrane porins: 1.3), it is unknown how their production is regulated. Recent work has established that diverse bacteria exploit a cell-cell communication device to regulate the transcription of multiple target genes. This communication device, termed 'quorum sensing', depends on the production of one or more diffusible signalling molecules termed' autoinducers ' that enable a bacterium to monitor its own cell population density. Quorum sensing is thus an example of multicellular behaviour in prokaryotes and re§ulates diverse physiological processes in animal, fish and plant pathogens . Analysis of the genome sequence of H pylori revealed that it contained a homologue of one of the identified autoinducer synthases, LuxS • The chemical nature of the autoinducer synthesized by LuxS is unknown, but it appears to play a role in the regulation of the transition from a nonpathogenic existence outside a host to a pathogenic existence inside a host for Salmonel/a, although the precise nature of this regulation is unknown. Given the paucity of regulatory systems identified in H pylori, it therefore follows that LuxSH is likely to play an active role in gene regulation enabling H pylori to su~cessfully establish an infection in the human stomach. We describe the cloning of luxSHp , and demonstrate that it functionally complements the LuxS defective E. coli strain, DH5a. Molecular investigation of the cascade stimulated by the autoinducer will reveal targets for potential blocking agents, offering exciting new strategies for controlling bacterial infection via targets that are not susceptible to conventional antibiotic resistance mechanisms. References I.Berg, D., Hoffman, P.S, Appelmelk, B.1., Kusters, J.G. (1997) TIMS 5:468-474 2.Hardman, A.M., Stewart, G.S.A.B, Williams, P. (1998) Antonie van Leeuwenhoek 74:199-210. 3.Moran, A. (1995) FEMS Immuno. Med. Micro. 10:271 280. 4.Surette, M.G., Miller, M.B, Bassler, B.L. (1999) Proc. Natl. Acad. Sci. 96:1639-1644 5.Tomb, J-F. et al. (1998) Nature 388:539-547