Diminished LcrV secretion attenuates Yersinia pseudotuberculosis virulence.
Many gram-negative bacterial pathogenicity factors that function beyond the outer membrane are secreted via a contact-dependent type III secretion system. Two types of substrates are predestined for this mode of secretion, namely, antihost effectors that are translocated directly into target cells and the translocators required for targeting of the effectors across the host cell membrane. N-terminal secretion signals are important for recognition of the protein cargo by the type III secretion machinery. Even though such signals are known for several effectors, a consensus signal sequence is not obvious. One of the translocators, LcrV, has been attributed other functions in addition to its role in translocation. These functions include regulation, presumably via interaction with LcrG inside bacteria, and immunomodulation via interaction with Toll-like receptor 2. Here we wanted to address the significance of the specific targeting of LcrV to the exterior for its function in regulation, effector targeting, and virulence. The results, highlighting key N-terminal amino acids important for LcrV secretion, allowed us to dissect the role of LcrV in regulation from that in effector targeting/virulence. While only low levels of exported LcrV were required for in vitro effector translocation, as deduced by a cell infection assay, fully functional export of LcrV was found to be a prerequisite for its role in virulence in the systemic murine infection model.
Bröms
Jeanette E
JE
Department of Medical Countermeasures, Swedish Defence Research Agency, Division of NBC-Defence, SE-901 82 Umeå, Sweden.
Francis
Matthew S
MS
Forsberg
Ake
A
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009690:Nucleic Acid Conformation; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000378:metabolism*; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics; D014774:Virulence; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D015012:Yersinia pseudotuberculosis Infections / Q000382:microbiology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C043908:LcrV protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; D012329:RNA, Bacterial; C074427:lcrQ protein, Yersinia pseudotuberculosis