A new role for lipoproteins LpqZ and FecB in orchestrating mycobacterial cell envelope biogenesis

ABSTRACT: Accounting for more deaths than any other bacterial species, Mycobacterium tuberculosis (Mtb) represents a critical threat to public health worldwide. A key factor contributing to Mtb's virulence is its unique cell envelope, which acts as a protective barrier. Among the components of this envelope, lipoproteins represent a critical but understudied group of proteins. In this study, we focused on 79 conserved putative lipoproteins, shared between Mtb and the closely related M. marinum. Leveraging the CRISPR/Cas9 gene editing system for Mycobacteria, we generated frameshift mutations, targeting one conserved lipoprotein-coding gene at a time. We found two mutants, lpqZ and fecB, that showed increased susceptibility to all tested antibiotics, pointing towards critical roles in cell envelope biogenesis. Using co-immunoprecipitation (Co-IP) followed by mass spectrometry (MS), we identified interacting partners of these two lipoproteins, indicating that they are key players in LAM and arabinogalactan synthesis, thus explaining the observed phenotypes.

INSTRUMENT(S):

ORGANISM(S): Mycobacterium Marinum Atcc Baa-535 Bacteria

DISEASE(S): Tuberculosis

SUBMITTER: Thang Pham  

LAB HEAD: Dr Connie Jimenez

PROVIDER: PXD069594 | Pride | 2025-12-12

REPOSITORIES: Pride