5wam

Publication Abstract from PubMed

The beta-barrel assembly machinery (BAM) is a conserved multi-component protein complex responsible for the biogenesis of beta-barrel outer membrane proteins (OMPs) in Gram-negative bacteria. Given its role in the production of OMPs for survival and pathogenesis, BAM represents an attractive target for the development of therapeutic interventions including drugs and vaccines against multi-drug resistant bacteria such as Neisseria gonorrhoeae The first structure of BamA, the central component of BAM, was from N. gonorrhoeae, the etiological agent of the sexually transmitted disease gonorrhea. To aid in pharmaceutical targeting of BAM, we expanded our studies to BamD and BamE within BAM of this clinically relevant human pathogen. We found that the presence of BamD, but not BamE, is essential for gonococcal viability. However, BamE, but not BamD, was cell-surface displayed under native conditions, yet in the absence of BamE, BamD indeed becomes surface exposed. Loss of BamE altered cell envelope composition leading to slower growth and increase in both antibiotic susceptibility and formation of membrane vesicles containing greater amounts of vaccine antigens. Both BamD and BamE are expressed in diverse gonococcal isolates, under host-relevant conditions, and throughout different phases of growth. The solved structures of Neisseria BamD and BamE share overall folds with E. coli proteins yet contain differences that may be important for function. Together, these studies highlight that while BAM is conserved across Gram-negative bacteria, structural and functional differences do exist across species, which may be leveraged in the development of species-specific therapeutics in the effort to combat multi-drug resistance.

Structural and functional insights into the role of BamD and BamE within the beta-barrel assembly machinery in Neisseria gonorrhoeae.,Sikora AE, Wierzbicki IH, Zielke RA, Ryner RF, Korotkov KV, Buchanan SK, Noinaj N J Biol Chem. 2017 Dec 11. pii: RA117.000437. doi: 10.1074/jbc.RA117.000437. PMID:29229778^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.