Comparative Global Gene Expression Profiles of Wild-TypeYersinia pestisCO92 and Its Braun Lipoprotein Mutant at Flea and Human Body Temperatures

Abstract

Braun/murein lipoprotein (Lpp) is involved in inflammatory responses and septic shock. We previously characterized a Δlpp mutant of Yersinia pestis CO92 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 WT Y. pestis and its Δlpp mutant 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 of lpp mutation on the transcriptomes of Y. pestis grown at 37 versus 26°C. While the absence of Lpp resulted mainly in the downregulation of metabolic genes at 26°C, the Y. pestis Δlpp mutant cultured at 37°C exhibited profound alterations in stress response and virulence genes, compared to WT bacteria. We investigated one of the stress-related genes (htrA) downregulated in the Δlpp mutant relative to WT Y. pestis. Indeed, complementation of the Δlpp mutant with the htrA gene restored intracellular survival of the Y. pestis Δlpp mutant. Our results support a role for Lpp in Y. pestis adaptation to the host environment, possibly via transcriptional activation of htrA.

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

“…1). In our previous study, we also demonstrated that the ⌬lpp mutant of Y. pestis was defective in surviving in macrophages, and the defect was related to decreased expression of the gene encoding the global stress protein GsrA (61). Perhaps decreased production of GsrA, or a related stress response protein, is responsible for poor intracellular survival of the ⌬msbB mutants as well.…”

Deletion of Braun Lipoprotein and Plasminogen-Activating Protease-Encoding Genes Attenuates Yersinia pestis in Mouse Models of Bubonic and Pneumonic Plague

“…In our earlier study, we have shown that the ⌬lpp single mutant was also unable to survive within macrophages due to the downregulation of a gene encoding the global stress response protein A (GsrA) (35,51). However, it is unclear how Pla directly or indirectly contributes to bacterial survival in the host cell, but the literature indicates that Pla can enhance bacterial invasion of epithelial cells and mediate the delivery of T3SS effectors into the host (34).…”

New Insights into Autoinducer-2 Signaling as a Virulence Regulator in a Mouse Model of Pneumonic Plague

“…Since orthologs of the Rbs operon are also associated with AI-2 transport, we examined the effect of combinatorial deletion of lpp , msbB , and rbsA on the levels of AI-2 in the culture supernatants of mutants versus the level in the supernatant of WT CO92. At temperatures of both 28°C (flea) and 37°C (human body), representing two lifestyles of Y. pestis (23), there were major aberrations in the patterns of AI-2 in the highly attenuated mutants (the Δ lpp Δ msbB and Δ lpp Δ msbB ΔrbsA mutants) compared to its occurrence in WT CO92 that were independent of the bacterial growth rates (data not shown). Interestingly, deletion of rbsA from the Δ lpp Δ msbB mutant had a potentiating effect on disrupting AI-2 patterns.…”

“…Since the deletion of the lpp and msbB genes from Y. pestis could possibly affect the topology of the bacterial membrane and/or the expression of the stress response genes (23), we evaluated changes in the AI-2 levels of mutants with a deletion in the canonical AI-2 transport system both singly ( lsrA ) and in combination with rbsA . The lsrA gene, which encodes the ATPase component of the Lsr ABC transporter complex, was chosen because of the similarity of its function to that of RbsA, which is also an ATPase for the RbsBAC transporter complex.…”