Job contenders: roles of the β‐barrel assembly machinery and the translocation and assembly module in autotransporter secretion

Abstract

SummaryIn Gram-negative bacteria, autotransporters secrete effector protein domains that are linked to virulence. Although they were once thought to be simple and autonomous secretion machines, mounting evidence reveals that multiple factors of the bacterial envelope are necessary for autotransporter assembly. Secretion across the outer membrane of their soluble effector "passenger domain" is promoted by the assembly of an outer membrane-spanning "b-barrel domain". Both reactions require BamA, an essential component of the b-barrel assembly machinery (BAM complex) that catalyzes the final reaction step by which outer membrane proteins are integrated into the lipid bilayer. A large amount of data generated in the last decade has shed key insights onto the mechanistic coordination of autotransporter b-barrel domain assembly and passenger domain secretion. These results, together with the recently solved structures of the BAM complex, offer an unprecedented opportunity to discuss a detailed model of autotransporter assembly. Importantly, some autotransporters benefit from the presence of an additional machinery, the translocation and assembly module (TAM), a two-membrane spanning complex, which contains a BamA-homologous subunit. Although it remains unclear how the BAM complex and the TAM cooperate, it is evident that multiple preparatory steps are necessary for efficient autotransporter biogenesis.

Autotransporter secretion exploits the bacterial actin-homologue

“…It is clear that the components impact upon many fundamental cellular process including ones with parallels across eukaryotes and prokaryotes such as the general secretion system and the cytoskeleton. The ability of MreB, like actin, to assemble and disassemble from filaments could provide a hitherto elusive propulsive force that enables ATs to traverse from the IM to the OM for secretion in the absence of ATP (10), and is substantiated by our observation that the interaction is dynamic and transient.…”

“…Although the main steps of AT secretion have been identified, many mechanistic details remain unresolved and are hotly debated (7,9,10). What at first appeared a selfsufficient secretion pathway has since been shown to comprise of multiple components including the inner membrane (IM) Sec translocon, periplasmic chaperones and the outer membrane (OM) β-barrel assembly machinery (BAM) complex or two-membrane spanning complex TAM (Translocation and assembly module).…”

“…How and where these components interact together to drive secretion remains to be elucidated, and could have a bearing on the overall building of the bacterial cell envelope because of the pleiotropic roles of the machineries involved. ATs bear 3 distinct domains: (i) the Sec-dependent signal sequence, that is located at the N-terminus, directs the secretion of the precursor across the IM; (ii) the central passenger domain that carries the functional site; and (iii) the carboxy terminal transporter domain, that inserts as a β-barrel into the OM and facilitates transport across the OM (10)(11)(12)(13).…”

An investigation into the Omp85 protein BamK in hypervirulent Klebsiella pneumoniae, and its role in outer membrane biogenesis

“…Previous structural and phylogenetic analyses (Heinz & Lithgow, 2014) suggested a model for the evolution of TamA through a gene duplication of bamA followed by an evolutionary process of sub-functionalization. This process of gradual change in one copy of the gene provides the means to ultimately encode a protein (TamA) that performs its function in a significantly different way (Shen et al, 2014, Selkrig et al, 2015, Bamert et al, 2017, to facilitate the process of outer membrane protein assembly in collaboration with BamA (Albenne & Ieva, 2017). In principle, bamK might represent an early event on an equivalent trajectory toward a further sub-functionalization.…”

“…Whereas B5055 thrives in murine serum, an isogenic mutant lacking the capsule secretion apparatus is totally inactivated by serum within an hour (Clements et al, ). The Wza capsule secretion pore appears to self‐assemble in the outer membrane (Dunstan et al, ), whereas most other outer membrane proteins are assembled by a highly sophisticated β‐barrel assembly machinery (BAM) composed of the core BAM complex (BAM ABCDE ) and the translocation and assembly module (the TAM) (Webb et al, , Plummer & Fleming, , Albenne & Ieva, , Noinaj et al, ). Each of these protein complexes is constituted around a membrane protein of the Omp85 protein family (BamA and TamA), and both are involved in the assembly of complex structures such as the adhesive fimbriae (Stubenrauch et al, , Stubenrauch et al, ) required by K. pneumoniae for biofilm formation (Klemm & Schembri, , Wilksch et al, , Khater et al, , Tan et al, ).…”