Hybrid Histidine Kinase Hk1 Is Part of a Two-Component System That Is Essential for Survival of Borrelia burgdorferi in Feeding Ixodes scapularis Ticks
Two-component signal transduction systems (TCS) are a principal mechanism used by bacteria to survey and adapt to perturbations in their surroundings. The Lyme disease spirochete, Borrelia burgdorferi, encodes only two TCS. Caimano et al. (p. 3117–3130) describe the two-component system comprised of Hk1, a hybrid histidine kinase, and Rrp1, a response regulator with diguanylate cyclase activity. Spirochetes lacking Hk1 are virulent in mice and able to migrate into ticks during feeding but are killed in the midgut following acquisition. hk1 mutants survive for prolonged periods within the midguts of unfed nymphs but are destroyed at the onset of the blood meal, indicating that the protective function(s) mediated by the Hk1/Rrp1 TCS is not tick life stage specific. Thus, spirochetes require the adaptive response initiated by bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) for survival within the tick during both acquisition and transmission.
Intracellular Pathogen Assay Identifies HSP82 as Important for Histoplasma Virulence
Histoplasma capsulatum is an intracellular fungal pathogen with few known virulence factors. To facilitate discovery of additional virulence factors by using forward genetics, Edwards et al. (p. 3348–3357) have developed an efficient, quantitative macrophage lethality screen based on activity of an enzymatic reporter transgene. This assay is applicable to a range of intracellular pathogens. Through this screen, they identify the HSP82 gene as required for full virulence of Histoplasma and demonstrate that expression of HSP82 enables yeast cells to tolerate infection-associated conditions, including thermal and oxidative stresses.
On and Off Switch of the Pneumococcal Pilus
The pneumococcal type 1 pilus is involved in virulence, adherence, inflammatory responses, and biofilm formation but is present in only a minority of strains, suggesting that this structure imparts fitness costs. Basset et al. (p. 2974–2983) show bistability of pilus expression (a reversible switch between on and off expression states) under the negative regulation of one of its structural components, the RrgA protein. This is the first demonstration of bistability within the pneumococcus as a mechanism to introduce heterogeneity within an isogenic population. Bistable expression of the pilus could provide a selective advantage for a subset of bacteria under different environmental conditions.
Postvaccination Antibodies Kill Salmonella enterica Serovar Typhi by Two Independent Mechanisms
Food- and waterborne spread of Salmonella enterica serovar Typhi causes approximately 21 million cases of typhoid fever annually. Although most people generate antibodies following typhoid infections or vaccination, the role of antibodies in clearance of S. Typhi has not been characterized. Lindow et al. (p. 3188–3194) define functional roles for human S. Typhi-specific antibodies produced postvaccination in the killing of wild-type S. Typhi by macrophages or complement.
Clostridium perfringens Enterotoxin Produces Systemic Effects and Lethality in Mice
Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of the second most commonly identified type of bacterial food poisoning. While this disease is usually self-limiting, severe outbreaks have involved deaths. To study systemic effects of CPE, Caserta et al. (p. 3020–3027) developed a model where CPE was inoculated into ligated small intestinal loops of mice. Dose-dependent intestinal damage, serum CPE, serum potassium, and lethality were observed. CPE was also found in the liver and kidney. These data suggest that CPE can be absorbed from the intestine into the circulation and then bind to internal organs to induce potassium leakage, which can cause death.
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