The low-Ca2+ response virulence regulon of human-pathogenic Yersiniae.

The Lcr is thought to function when the yersiniae infect their mammalian host (see Fig. 2). At present, all evidence points to roles of the Lcr in protecting the bacteria in extracellular niches. We can speculate that early in infection, the yersiniae experience a 37 degrees C extracellular, Ca(2+)-containing environment. Temperature-induction and down-modulation by Ca2+ would occur for Lcr genes, resulting in a cytotoxic and weakly anti-phagocytic surface on the bacteria. Yersiniae that are taken up into macrophages may find a low-Ca2+, inductive environment for expression and release of Yops and V antigen. Upon release from macrophages, the accumulated Yops may render the bacteria sufficiently anti-phagocytic to resist ingestion by neutrophils, and Lcr virulence proteins such as YopM, and perhaps V antigen and other Yops might act to dampen the inflammatory response and prevent secondary influxes of phagocytes. The abundant nucleotides from necrotic host cells undergoing nucleic acid breakdown might then promote extracellular growth. Even though Lcr virulence genes would be expressed at an intermediate level under these conditions, this may be sufficient for the continued undermining of the host natural defenses. It also is possible that there are additional environmental signals, not yet identified, that modulate Lcr virulence gene expression and permit strong expression in extracellular microenvironments that arise as a result of the host-yersiniae interactions.