Structural and functional insights into the role of BamD and BamE within the β-barrel assembly machinery in Neisseria gonorrhoeae

Aleksandra E. Sikora, Igor H. Wierzbicki, Ryszard A. Zielke, Rachael F. Ryner, Konstantin V. Korotkov, Susan K. Buchanan, Nicholas Noinaj

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The β-barrel assembly machinery (BAM) is a conserved multicomponent protein complex responsible for the biogenesis of β-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 multidrug-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; however, in the absence of BamE, BamD indeed becomes surface- exposed. Loss of BamE altered cell envelope composition, leading to slower growth and an 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 Escherichia coli proteins but contain differences that may be important for function. Together, these studies highlight that, although 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 multidrug resistance.

Original languageEnglish
Pages (from-to)1106-1119
Number of pages14
JournalJournal of Biological Chemistry
Volume293
Issue number4
DOIs
StatePublished - Jan 26 2018

Bibliographical note

Funding Information:
3 Supported by the Department of Biological Sciences at Purdue University, a Showalter Trust Award, and NIAID, National Institutes of Health Grant 1K22AI113078-01. To whom correspondence may be addressed. E-mail: [email protected].

Funding Information:
Acknowledgments—We thank the respective staffs at the National Institute of General Medical Sciences and National Cancer Institute Structural Biology Facility (GM/CA) beamline at the Advanced Photon Source (APS), Argonne National Laboratory, and at the X25 beamline at the National Synchrotron Light Source (NSLS), Brookhaven National Laboratory, for assistance. Use of the APS was supported by the United States Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38, and use of the NSLS was supported by the United States Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract DE-AC02-98CH10886.

Funding Information:
2 Supported by the Intramural Research Program of the NIDDK, National Insti-tutes of Health.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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