Francisella species are found throughout the Northern Hemisphere and infect a variety of vertebrate and invertebrate hosts [5, 6]. Infections with FT can be contracted from blood sucking insects, such as the deer fly [5, 7], mosquitoes [8, 9], and ticks [5, 7, 10], and by open-wound contact

with infected animal tissue [5, 11, 12]. Upon entry into a susceptible vertebrate host, FT is readily phagocytized by resident macrophages and dendritic cells and quickly escapes into the cytoplasm [13, 14] where it multiplies. selleck screening library Late in its replicative cycle, FT induces apoptotic death of the host phagocyte, resulting in release of progeny bacteria that can infect new host cells. Recent studies have shown that significant numbers of FT are found in the acellular plasma fraction of mice infected intradermally or intranasally with either FT Live Vaccine Strain (LVS) (Type B) or FT Schu S4 (Type A) [15], and intranasally with FT novicida [16]. These findings suggest that, in addition to utilizing the intracellular cytoplasmic niche for replication and protection CAL-101 cell line from humoral immunity, FT may also have a significant extracellular phase. Several studies have shown that deposition of host complement

component C3 on the surface of FT is required for opsonophagocytosis by activating CR3 and CR4-mediated phagocytosis by macrophages and dendritic cells [14, 17, 18]. It is also known that FT is relatively resistant to complement-mediated lysis [19]. A recent report suggested that resistance of FT to membrane attack complex-mediated lysis may be due (at least in part) to its ability to bind to factor H from host plasma [20]. Cediranib (AZD2171) It is possible that the ability of FT to bind to factor H and potentially to other host plasma components plays a significant role in its pathogenesis. It has been long established that a broad spectrum of both gram-positive and gram-negative bacterial pathogens gain a survival advantage by interacting

with components of the host coagulation/fibrinolytic system in humans [21–24]. For instance, the ability to acquire surface-associated plasmin has been documented as an important virulence mechanism in Group A Ralimetinib order streptococci [25], Borrelia burgdorferi [26], and Yersinia pestis [27] by aiding in the organism’s ability to penetrate the extracellular matrix and to disseminate to distal sites in the host. Plasminogen (PLG) is a 92-kDa glycoprotein zymogen that is involved in fibrinolysis. This precursor protein is converted to an active serine protease (plasmin) by cleavage of the peptide bond between residues R560and V561 in vivo via urokinase-type (uPA) and/or tissue-type (tPA) PLG activators. Plasmin has an important role in blood clot resolution because of its role in the degradation of fibrin polymers.