Two other proteins likely involved in cell morphology and peptidoglycan CHIR-99021 cost turnover were also decreased in abundance under in vivo conditions, the rod-shape determining membrane protein YfgA and the LysM domain protein YgaU. It remains to be demonstrated whether these changes represent a coordinated physiological response of SD1 cells to the hostile environment in the host gut, possibly promoting evasion from the immune system and lowering OM porosity for protection from any extracellular toxic substances released
by the host. S. dysenteriae type III secretion system and other virulence factors The virulence plasmid encodes the 30 kb spa-mxi type III secretion system (TTSS) and invasion plasmid antigens (Ipa proteins) required for invasion of host cells . The TTSS is comprised of a membrane-spanning protein complex which includes ca. 50 proteins, including Mxi and Spa proteins involved in assembly and regulation of the TTSS, chaperones (IpgA, IpgC, IpgE and Spa15), transcription activators (VirF, VirB and MxiE), translocators (IpaB, IpaC and IpaD) and ca. 25 effectors [8, 54]. Invasion is followed by entry of Shigella into colonic epithelium cells via the basolateral
membrane. Further bacterial invasion and lateral spreading of the bacteria within the colonic epithelium is mediated by host cell actin OICR-9429 supplier polymerization. The surface protein IcsA encoded by the virulence plasmid is responsible Cell Penetrating Peptide for actin-based BIBF 1120 nmr motility required for intra- and inter-cellular spread of the bacteria . Shigella manipulates the host innate and adaptive immune system via the Osp family of proteins . In the present study, we identified many components of the TTSS, including 15 Mxi-Spa proteins and 16 effectors and their chaperones (Additional File 1, Table S1). The TTSS has been reported as being assembled with a few effectors and chaperones when cultured in vitro, and activated only after contact of bacteria with host cells . Here, many TTSS proteins were identified in both the in vitro
and in vivo datasets, including membrane associated Mxi and Spa proteins, Ipa effectors and Spa chaperones. Spa15 is a chaperone for the Osp family of effectors (OspC1, OspC2, OspC3) and also for the IpaA and IpgB2 effectors; while IpgC is a chaperone for IpaB and IpaC . Activation of TTSS results in the induction of the transcription of genes encoding a second set of effectors under the control of MxiE and IpgC, including several spa genes. The OspC2 and OspC3 effectors and the IpgA and Spa32 proteins were detected only under in vivo conditions. Activation of the TTSS is followed by formation of the TTSS translocator pore which requires the IpaB, IpaC and IpaD effectors [5, 57]. IpaB in particular induces apoptosis in host macrophages leading to inflammatory infection .