Bacteria have mechanisms to export proteins for diverse purposes including colonization of hosts and pathogenesis. Perhaps erroneously, proteins called ‘autotransporters’ have long been considered as one of these protein secretion systems. Mounting evidence shows that autotransporters might be “substrates” to be secreted, not an autonomous-transporter system, and we have discovered a new Translocation and Assembly Module (the TAM) that promotes efficient secretion of autotransporters.
The TAM consists of an Omp85-family protein, TamA, in the outer membrane and another integral membrane protein, TamB, in the inner membrane of diverse bacterial species. TamA and TamB form a protein complex that can be purified by immunoprecipitation and mutangenesis has pin-pointed the TamA-TamB interaction surfaces, which are disabled with subtle changes. Mutants of Citrobacter rodentium, Klebsiella pneumoniae or Salmonella enterica lacking either the tamA or tamB gene have virulence defects, and biochemical analysis shows that they fail to secrete autotransporters; instead, the precursor form of the autotransporter accumulates in the periplasm of mutants lacking the TAM. We are currently working to decipher whether the TAM collaborates with the BAM complex to assemble autotransporters, and to fully characterize the novel mechanism by which the TAM drives nascent autotransporters into the hydrophobic core of the outer membrane. The discovery of the TAM provides a new target at which to aim the development of therapies to inhibit growth and colonization by bacterial pathogens.