Lipoproteins ofMycobacterium tuberculosis: an abundant and functionally diverse class of cell envelope components

Abstract

Mycobacterium tuberculosis remains the predominant bacterial scourge of mankind. Understanding of its biology and pathogenicity has been greatly advanced by the determination of whole genome sequences for this organism. Bacterial lipoproteins are a functionally diverse class of membrane-anchored proteins. The signal peptides of these proteins direct their export and post-translational lipid modification. These signal peptides are amenable to bioinformatic analysis, allowing the lipoproteins encoded in whole genomes to be catalogued. This review applies bioinformatic methods to the identification and functional characterisation of the lipoproteins encoded in the M. tuberculosis genomes. Ninety nine putative lipoproteins were identified and so this family of proteins represents ca. 2.5% of the M. tuberculosis predicted proteome. Thus, lipoproteins represent an important class of cell envelope proteins that may contribute to the virulence of this major pathogen.

BCG Vaccination Induces Robust CD4+ T Cell Responses to Mycobacterium tuberculosis Complex–Specific Lipopeptides in Guinea Pigs

“…In a second step, the signal peptidase, LspA, cleaves off the N-terminal signal peptide. Finally the acylated cysteine is additionally lipidated at its free amino group by the N-acyltransferase, Lnt (35). The triacylated N terminus anchors the mature lipoprotein to the bacterial cell membrane but can be further processed: for some lipoproteins, cleavage sites have been described that allow for an enzymatic shedding of the protein, which leaves the lipidated N terminus tethered to the cell membrane (36,37).…”

Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold ‘em, knowing when to fold ‘em

“…Lipoprotein functions in Gram-positive bacteria Bioinformatic analyses (as described earlier) have indicated that lipoproteins are a relatively abundant family of proteins, typically representing 2% or more of a Grampositive bacterial proteome [18,19,43,54,57]. Functional analyses have revealed several recognisable functional groupings of Gram-positive bacterial lipoproteins [3], with these functions reflecting the localisation of lipoproteins within the cell envelope and more specifically at the interface between the membrane and the cell wall (Box 3).…”

“…Bioinformatic analysis indicates that Tat translocation of lipoproteins is widespread in the genus Streptomyces with up to 20% of putative lipoproteins being exported via Tat in the four currently sequenced Streptomyces species (M.I.H and I.C.S, unpublished). In comparison, $10%-15% of the putative lipoproteins of M. tuberculosis [18] are predicted to be Tat substrates, whereas only two of the 41 putative lipoproteins in the actinomycete Leifsonia xyli [19] are predicted to be Tat substrates (I.C. S, unpublished).…”

“…Moreover, genome analyses have consistently identified putative lipoproteins predicted to have important roles in cell envelope stability and cell wall cross-linking or remodelling such as penicillin binding proteins and peptidoglycan hydrolases [18,54]. For example, ErfK domain (PFAM PF03734) L,D transpeptidases were recently discovered to have roles in the alternative 3-3 cross-linking of peptidoglycan in Enterococcus faecium and M. tuberculosis [72,73], perhaps as a way of recycling or remodelling the peptidoglycan.…”

“…Many bacterial genomes encode several representatives of this family, a subset of which are predicted to be lipoproteins. For example, two of the four ErfK domain proteins in the M. tuberculosis H37Rv genome are predicted to be lipoproteins [18], as are all six encoded in the S. coelicolor genome. Two ErfK proteins in E. coli have also been demonstrated to cross-link Braun's lipoprotein to the peptidoglycan [74] and so an additional possibility is that some members of this family are responsible for cell wall anchoring of proteins in a manner analogous to sortases [31].…”