While the biogenesis of OMVs is poorly understood, it is thought that expansion of the outer leaflet of the membrane relative to the inner leaflet induces membrane curvature that forces the outer membrane to bud away from the cell. OMV production can be detected in bacterial communities growing under a variety of conditions, including planktonic cultures as well as in surface-attached biofilm communities. OMVs are produced by both pathogenic and non-pathogenic bacteria. OMVs released by pathogens can contain multiple components that interact with the host, including LPS, virulence factors, and other antigens. Pathogen-derived OMVs may contribute to virulence by modulating the innate immune response, delivering toxins to cells, dispersing antigens and virulence factors away from the bacterium, trafficking signaling molecules between bacteria, and more. Microscopic examination of tissues has detected the presence of OMVs near host cells or within host tissues, suggesting an interaction between OMVs and the host during infection. Further, OMVs have been found to deliver active toxins to host cells, including the enterotoxigenic E. coli heat-labile enterotoxin, the enterohemorrhagic E.coli pore-forming cytotoxin ClyA, and the H. pylori VacA protein. Environmental stresses contribute to the production of OMVs, suggesting that, as bacteria encounter stressors such as those found within the infected host, the production of OMVs may not only manipulate interactions with the host but also aid in the survival of the bacterium. The Gram-negative bacterium Yersinia pestis, a pathogen of both insects and mammals, can be transmitted to humans via the bite of hematophagous insects or through the inhalation of respiratory droplets or aerosols containing the bacteria, and can cause bubonic, pneumonic, or septicemic plague. Temperature is a major regulator of gene expression in Y. pestis, controlling both transcriptional and post-transcriptional responses. At lower temperatures, Y. pestis produces factors that maximize survival and colonization in the flea, such as biofilms, while at higher temperatures, the bacterium expresses genes required for mammalian infection, including the adhesin Ail, the F1 fimbrial antigen, the outer membrane protease Pla, and the Yop-Ysc type III secretion system. Thus, Y. pestis possesses a variety of virulence factors, including a PF-4217903 number of outer membrane-associated factors, which are necessary for interacting with its hosts to ultimately cause disease. Among these, the Pla protease is necessary for the progression of both bubonic and pneumonic plague, but is dispensable during septicemic plague. Pla is known to cleave a number of mammalian host proteins, including the zymogen plasminogen, the plasmin inhibitor a2-antiplasmin, and the recently identified substrate Fas ligand, a major inducer of host cell death via apoptosis.