Comparative Global Gene Expression Profiles of Wild-TypeYersinia pestisCO92 and Its Braun Lipoprotein Mutant at Flea and Human Body Temperatures
Braun/murein lipoprotein (Lpp) is involved in inflammatory responses and septic shock. We previously characterized aΔlppmutant ofYersinia pestisCO92 and found that this mutant was defective in surviving in macrophages and was attenuated in a mouse inhalation model of plague when compared to the highly virulent wild-type (WT) bacterium. We performed global transcriptional profiling of WTY. pestisand itsΔlppmutant using microarrays. The organisms were cultured at 26 and 37 degrees Celsius to simulate the flea vector and mammalian host environments, respectively. Our data revealed vastly different effects oflppmutation on the transcriptomes ofY. pestisgrown at 37 versus26C. While the absence of Lpp resulted mainly in the downregulation of metabolic genes at26C, theY. pestis Δlppmutant cultured at37Cexhibited profound alterations in stress response and virulence genes, compared to WT bacteria. We investigated one of the stress-related genes (htrA) downregulated in theΔlppmutant relative to WTY. pestis. Indeed, complementation of theΔlppmutant with thehtrAgene restored intracellular survival of theY. pestis Δlppmutant. Our results support a role for Lpp inY. pestisadaptation to the host environment, possibly via transcriptional activation ofhtrA.