9.B.138 The Putative Mycobacterial Outer Membrane Porin, LprG (LprG; P27) Family

The P27-P55 (lprG-Rv1410c) operon is crucial for the survival of Mycobacterium tuberculosis during infection in mice. P55 encodes an MFS efflux pump (2.A.1.3.34) that has been shown to provide Mycobacterium smegmatis and Mycobacterium bovis BCG with resistance to several drugs, while P27 encodes a mannosylated lipoglycoprotein, previously described as an antigen that modulates the immune response against mycobacteria.

P27 and P55 function together through an efflux-pump mechanism. Deletion of the P27-P55 operon made M. tuberculosis susceptible to sodium dodecyl sulfate, suggesting that the lack of these proteins causes alterations in the cell wall permeability of the bacterium. Both P27 and P55 are required to restore wild type drug resistance phenotypes in the mutant (Bianco et al., 2011; Farrow and Rubin, 2008). LprG and LppX have been suggested to function as carriers of lipids, glycolipids or their derviatives in outer membrane biogenesis (Luthra et al., 2011). 

MmpL (mycobacterial membrane protein large) proteins are integral membrane proteins that have been implicated in the biosynthesis and/or transport of mycobacterial cell wall lipids. Nisbett et al. 2023 examined the relationship between two lipid transport pathways associated with the proteins MmpL11 and LprG-Rv1410c. The lipoprotein LprG interacts with proteins involved in cell wall processes including MmpL11, which is required in biofilms for the surface localization of certain lipids. Nisbett et al. 2023 reported that deletion of mmpL11 (MSMEG_0241) or the lprG-rv1410c operon homologues (MSMEG_3070-3069 in Mycobacterium smegmatis) produced similar biofilm defects that were distinct from that of the previously reported mmpL11 transposon insertion mutant. Analysis of pellicle biofilms, bacterial growth, lipid profiles, and gene expression revealed that the biofilm phenotypes could not be directly explained by changes in the synthesis or localization of biofilm-related lipids or the expression of biofilm-related genes. Instead, the shared biofilm phenotype between ΔMSMEG_3070-3069 and ΔmmpL11 may be related to their modest growth defect.


 

References:

Bianco, M.V., F.C. Blanco, B. Imperiale, M.A. Forrellad, R.V. Rocha, L.I. Klepp, A.A. Cataldi, N. Morcillo, and F. Bigi. (2011). Role of P27 -P55 operon from Mycobacterium tuberculosis in the resistance to toxic compounds. BMC Infect Dis 11: 195.

Farrow, M.F. and E.J. Rubin. (2008). Function of a mycobacterial major facilitator superfamily pump requires a membrane-associated lipoprotein. J. Bacteriol. 190: 1783-1791.

Luthra, A., G. Zhu, D.C. Desrosiers, C.H. Eggers, V. Mulay, A. Anand, F.A. McArthur, F.B. Romano, M.J. Caimano, A.P. Heuck, M.G. Malkowski, and J.D. Radolf. (2011). The transition from closed to open conformation of Treponema pallidum outer membrane-associated lipoprotein TP0453 involves membrane sensing and integration by two amphipathic helices. J. Biol. Chem. 286: 41656-41668.

Nisbett, L.M., M.L. Previti, and J.C. Seeliger. (2023). A Loss of Function in LprG-Rv1410c Homologues Attenuates Growth during Biofilm Formation in. Pathogens 12:.

Examples:

TC#NameOrganismal TypeExample
9.B.138.1.1

LprG (P27) lipoprotein

Bacteria

LprG of Mycobacterium tuberculosis (P0A518)

 
9.B.138.1.2

LppX lipoprotein

Bacteria

LppX of Mycobacterium tuberculosis (P65306)