Response of Leptospira interrogans to Physiologic Osmolarity: Relevance in Signaling the Environment-to-Host Transition

Abstract

Transmission of pathogenic Leptospira between mammalian hosts usually involves dissemination via soil or water contaminated by the urine of carrier animals. The ability of Leptospira to adapt to the diverse conditions found inside and outside the host is reflected in its relatively large genome size and high percentage of signal transduction genes. An exception is Leptospira borgpetersenii serovar Hardjo, which is transmitted by direct contact and appears to have lost genes necessary for survival outside the mammalian host. Invasion of host tissues by Leptospira interrogans involves a transition from a low osmolar environment outside the host to a higher physiologic osmolar environment within the host. Expression of the lipoprotein LigA and LigB adhesins is strongly induced by an upshift in osmolarity to the level found in mammalian host tissues. These data suggest that Leptospira utilizes changes in osmolarity to regulate virulence characteristics. To better understand how L. interrogans serovar Copenhageni adapts to osmolar conditions that correspond with invasion of a mammalian host, we quantified alterations in transcript levels using whole-genome microarrays. Overnight exposure in leptospiral culture medium supplemented with sodium chloride to physiologic osmolarity significantly altered the transcript levels of 6% of L. interrogans genes. Repressed genes were significantly more likely to be absent or pseudogenes in L. borgpetersenii, suggesting that osmolarity is relevant in studying the adaptation of L. interrogans to host conditions. Genes induced by physiologic osmolarity encoded a higher than expected number of proteins involved in signal transduction. Further, genes predicted to encode lipoproteins and those coregulated by temperature were overrepresented among both salt-induced and salt-repressed genes. In contrast, leptospiral homologues of hyperosmotic or general stress genes were not induced at physiologic osmolarity. These findings suggest that physiologic osmolarity is an important signal for regulation of gene expression by pathogenic leptospires during transition from ambient conditions to the host tissue environment.

Transcriptional Response ofLeptospira interrogansto Iron Limitation and Characterization of a PerR Homolog

“…Expression of the gene encoding LA0572, predicted to be involved in transport of ferrienterobactin (55), and expression of the gene encoding LA2242, a desferrioxamine receptor homolog, were upregulated (Table 2), similar to what was found in L. biflexa (44). Expression of la2242 is also induced by transition from low to physiological osmolarity conditions (48) and exposure to serum (57).…”

Sodium Chloride Affects Helicobacter pylori Growth and Gene Expression

“…For pathogenic bacteria, osmotic stress can also serve as a signal that controls expression of virulence factors. Specifically, it has been suggested that sodium chloride concentration serves as a cue for the regulation of virulence in Listeria monocytogenes (10,20) and Leptospira interrogans (17). In keeping with this, a recent study showed that elevated salt concentrations result in alterations in expression of the virulence factor CagA in H. pylori strain 26695 (16).…”

Multiple Posttranslational Modifications of Leptospira biflexa Proteins as Revealed by Proteomic Analysis

“…No large-scale microarray data or extensive proteomic analyses have been reported for the saprophyte, although Thongboonkerd and colleagues compared total protein lysate of L. biflexa to multiple pathogenic strains to identify potential virulence factors (10). In contrast, extensive microarray and proteomic studies have been performed on various host-associated species (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). These limitations in our basic knowledge of L. biflexa reduce its utility as a model organism, since there are no known protein markers for the outer membrane and no abundantly synthesized proteins have been reported.…”