It is reasonable selleckchem to suspect that modification of the PV microenvironment by additional secretion systems is also important in C. burnetii host cell parasitism. Gram-negative bacteria can employ several secretion systems to translocate proteins into the extracellular milieu . However, bioinformatic analysis of the C. burnetii genome reveals canonical components of only a type I secretion system with the presence of a tolC homolog [18, 19]. Type I secretion is typically a one step process that transports proteins directly from the bacterial cytoplasm
into the surrounding environment . However, a small number of proteins, such as heat-stable enterotoxins I and II of Nutlin-3a cost Escherichia coli[21, 22], and an ankyrin repeat protein of Rickettsia typhi, appear to access TolC via the periplasm after transport across the inner membrane by the Sec translocase. C. burnetii lacks typical constituents of a type II secretion system . However, the organism encodes several genes involved in type IV pili (T4P) assembly, several of which are homologous to counterparts of type II secretion systems, indicating a common evolutionary
origin and possibly a similar function . Accumulating data indicates core T4P proteins can constitute a secretion system [26–30]. In Francisella novicida, a collection of T4P proteins form a secretion system that Selleck PCI-32765 secretes at least 7 proteins . In Vibrio cholerae, T4P secrete a soluble colonization factor required for optimal intestinal colonization of infant mice . Dichelobacter nodosus secrete proteases in a T4P-dependent manner [29, 31]. Like the well-studied type II secretion system of Legionella pneumophila, a close phylogenetic relative of C. burnetii,
substrates secreted by T4P are biased towards N-terminal signal sequence-containing enzymes [27, 32]. C. burnetii encodes several enzymes with predicted signal Adenylyl cyclase sequences, such as an acid phosphatase (CBU0335) that inhibits neutrophil NADPH oxidase function and superoxide anion production [33, 34]. Along with PV detoxification, C. burnetii exoenzymes could presumably degrade macromolecules into simpler substrates that could then be transported by the organism’s numerous transporters . Genome analysis indicates C. burnetii possesses a complete Sec translocase for translocation of signal sequence-containing proteins into the periplasm [18, 19]. Another secretion mechanism employed by Gram-negative bacteria is release of outer membrane vesicles (OMVs). OMVs capture periplasmic components before the vesicle pinches off from the cell envelope. This ‘packaging’ of proteins is thought to provide a protective environment for delivery of the contents. OMVs are implicated in a variety of functions including delivery of virulence factors, killing of competing bacteria, and suppression of host immune responses [35, 36]. The discovery of host cell-free growth of C.