The Twin-Arginine Translocation Pathway of Mycobacterium smegmatis Is Functional and Required for the Export of Mycobacterial β-Lactamases

Abstract

Tuberculosis, caused by the bacillus Mycobacterium tuberculosis, remains a global health problem accounting for over two million deaths annually (23). The ability to survive in host phagocytes is a poorly understood virulence property of M. tuberculosis. The M. tuberculosis proteins exported to the bacterial cell surface or secreted by the bacillus are ideally positioned to interact with host cell components and include virulence factors that promote intracellular survival.

The Bacterial Twin-Arginine Translocation Pathway

“…In fact, tatC may be an essential gene for optimal growth in these bacteria (83,117). Recently, using β-lactamase as a reporter for Tat transport, McDonough et al (83) demonstrated that the phospholipase C proteins (PlcA and PlcB), important for the virulence of M. tuberculosis (83,104), are exported via the Tat pathway.…”

“…Mycobacterium tuberculosis and Mycobacterium smegmatis tat mutants were unable to transport active β-lactamases (83). In fact, tatC may be an essential gene for optimal growth in these bacteria (83,117).…”

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

“…In the high Guanine+Cytosine branch of Gram-positive bacteria known as actinomycetes, Tat is also apparently required for the translocation of lipoproteins, including the BlaC b-lactamase putative lipoprotein of Mycobacterium tuberculosis when it is expressed in M. smegmatis [16] and four putative lipoproteins in the model actinomycete, Streptomyces coelicolor [17]. 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of putative lipoproteins being exported via Tat in the four currently sequenced Streptomyces species (M.I.H and I.C.S, unpublished).…”

Potentiation of Available Antibiotics by Targeting Resistance – An Emerging Trend in Tuberculosis Drug Development

“…lactamase activity has been reported in all known mycobacterial species (Kasik, 1979), except the non-pathogenic M. fallax, which exhibits hypersusceptibility to lactams (Quinting et al, 1997). Mycobacteria, including M. tuberculosis, export lactamases to the cell wall via the twin-arginine translocation (Tat) pathway (McDonough et al, 2005, Voladri et al, 1998, thus disruption of the Tat transporter leads to lower lactamase activity in M. smegmatis culture filtrates and increased lactam susceptibility (McDonough et al, 2005). The major lactamase in M. tuberculosis, BlaC, is a member of the Ambler Class-A lactamases and exhibits broad substrate specificity, catalysing hydrolysis of both cephalosporins and penicillins (Voladri et al, 1998, Wang et al, 2006.…”