However, some genes, such as pyrD (LIC13433), kdpA (LIC10990), and sdhA (LIC12002), buy CP-868596 did not have the same levels of expression as other genes within their putative operons. A possible explanation could be due to transcriptional polarity , where the level of expression of distal genes is less than that of promoter-proximal genes. In addition, the expression of the constituent genes in an operon may sometimes be discoordinated at the suboperonic level by the presence of internal promoters, differential
translational efficiency, or differential instability of regions of a polycistronic mRNA . This allows a subset of the operon to be separately transcribed as an internal mini-operon in response to different signals. Finally, most predicted operons have not been verified experimentally,
and the genes therein can in reality be transcribed independently. The definite answer to these various possibilities must await further investigation. Complement resistance and other virulence determinants Complement-resistant L. interrogans serovar Copenhageni was used in our study. Previous reports demonstrated that complement resistance of pathogenic Leptospira is related to factor H-binding, degradation of C3b and C3 convertase, and inhibition of membrane-attack complex deposition [24, 38]. Factor H acts as a complement regulator by binding to C3b and displacing Bb from C3 convertases, thereby promoting factor I in cleaving C3b into its inactive form, iC3b . Binding to factor H is one of the mechanisms that click here bacteria utilize to evade complement killing . LfhA (also known as LenA) and LenB of L. interrogans were previously shown to interact with factor H [24, 61]. However, in our study, genes encoding these factor H-binding proteins were not significantly up-regulated. With the exception of LigB, other known or
potential virulence determinants that play a role in motility, chemotaxis, colonization or adhesion were not found to be up-regulated after exposure to serum. These include extracellular matrix binding proteins, enzymes capable of host cell membrane degradation such as sphingomyelinase, phosphatase, and hemolysin, as well as surface proteins previously shown to be expressed in vivo, including OmpL1, LipL41, LipL32, LipL21, LipL46, Loa22, and Lsa21, [17, 19–23, 25–27, 33, 34, 90, 91]. In addition, recent studies Suplatast tosilate using genome-wide transposon mutagenesis of L. interrogans revealed novel virulence genes, LA1641 (or LIC12143) and LA0615 (or LIC12967), which resulted in attenuation in hamsters when the genes were insertionally inactivated . Neither gene was differentially expressed in our experiments. While it is possible that some virulence-associated proteins may be expressed constitutively or regulated at the post-transcriptional level, transcription of some genes may also be influenced by the presence or absence of components in the EMJH medium.