Autotransporters (ATs) compose a large superfamily of proteins produced by Gram-negative bacteria (47). They consist of an N-terminal signal sequence, a """"""""passenger domain"""""""" that mediates the protein's effector function, and a C-terminal """"""""p-domain"""""""" involved in translocation of the passenger domain across the outer membrane. """"""""Classical"""""""" ATs are monomeric with (3-domains of ~26o aa, while trimeric ATs have (3-domains of -70 aa, three of which form the outer membrane p-barrel structure (47). Classical ATs include the IgA protease ofNeisseria gonorrhoeae, IcsA of Shigellaflexneri, pertactin of Bordetella pertussis, and the serine protease autotransporters of enterpbacteriaceae (SPATEs) (69). Trimeric ATs include YadA of Yersinia species and Hia of Haemophilus influenzae, both of which are involved in adherence (69). Two Partner Secretion (TPS) systems, also widespread among Gram-negative bacteria, are conceptually similar to ATs, except the passenger and p-domains are synthesized as separate proteins known generically as the TpsA and TpsB family members, respectively (104). The TpsA """"""""exoprotein"""""""" often is synthesized with a prodomain at either the N- or C-terminus that is removed during translocation, and while some TpsA proteins are released into the extracellular environment, others remain anchored to the cell surface (66,105) ((122,133). Predicting the presence of a pro-domain, whether the mature protein will be released, and, if not, its topology on the cell surface currently is not possible. Functions associated with TpsA proteins include adherence, cytotolysis, heme uptake, and contact-dependent growth inhibition (69). The B. pseudomallei K96243 genome (71) contains 10 putative AT-encoding genes and one TPSencoding locus. One AT, the BPSS1492 or bimA gene product, induces actin polymerization, allowing B. pseudomallei to move within eukaryotic cells'cytoplasm (138). Neither the other AT-encoding OPvFs, nor the genes encoding the putative TPS system, which we named btpA and btpB, have been studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI065359-09
Application #
8462549
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
9
Fiscal Year
2013
Total Cost
$524,057
Indirect Cost
$49,556
Name
University of California Irvine
Department
Type
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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