A periplasmic protein complex mediates arabinofuranosyltransferase activity and intrinsic drug resistance in Mycobacterium tuberculosis
Year: 2026
Type: article
Abstract: (Mtb) is a major barrier to effective tuberculosis (TB) treatment and is largely due to its complex, impermeable cell envelope. We identified a periplasmic protein complex comprising FecB and Rv3035 that is essential for maintaining envelope integrity and mediating intrinsic multidrug resistance in Mtb. FecB interacts with Rv3035, forming a stable heterodimer that associates with the cell envelope biosynthesis protein AftB. We report the structures of Rv3035 alone and in complex with FecB and identify critical residues for complex formation and function. Coessentiality and genetic interaction analyses support a functional link between FecB, Rv3035, and AftB, an arabinofuranosyltransferase that synthesizes arabinogalactan and lipoarabinomannan. Loss of FecB or Rv3035 disrupted AftB-mediated arabinan synthesis, suggesting that these proteins support AftB's enzymatic activity. FecB is required for Mtb virulence in mice, underscoring its physiological relevance. These findings highlight FecB, Rv3035, and AftB as promising therapeutic targets.
Source: Science Advances
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: Pathway Analysis in Tuberculosis, UC San Diego FIRST Program, Joan & Sanford I. Weill Medical College of Cornell University - to identify new drug targets with the potential to shorten the treatment of TB patients, Structure-based Discovery of Critical Vulnerabilities of Mycobacteria, Graduate Research Fellowship Program (GRFP), G9000091560, G9000284805, G9000353838, Assembly and export of mycobacterial lipoglycans, T32 for Training in Microbiology & Infectious Diseases
OpenAlex ID: W7147720454