Abstract

We will examine the biochemical and genetic factors that determine the level of resistance of Neisseria gonorrhoeae to the oxygen independent antimicrobial systems of the human PMN. We will purify antimicrobial proteins from PMN granule extracts by sequential ion-exchange and molecular-sieve chromatography. Purified proteins will be tested for antimicrobial activity against isogenic strains that contain defined mutations which affect cell envelope structure. Genetic derivatives that exhibit increased resistance or sensitivity to granule proteins will be isolated and analyzed for alterations in outer membrane proteins and lipopolysaccharide. These mutants will then be used to construct isogenic pairs that differ in resistance to granule proteins. This information will allow us to define those cell surface structures involved in determining the resistance of the gonococcus to the oxygen independent microbiocidal systems of the PMN. The results obtained from this analysis will increase our knowledge regarding the structural-functional relationships of the gonococcal cell envelope and will advance our understanding of the host and bacterial factors which regulate gonococcal pathogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021150-03
Application #
3131075
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1984-04-01
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Ohneck, Elizabeth A; Goytia, Maira; Rouquette-Loughlin, Corinne E et al. (2015) Overproduction of the MtrCDE efflux pump in Neisseria gonorrhoeae produces unexpected changes in cellular transcription patterns. Antimicrob Agents Chemother 59:724-6
Unemo, Magnus; Shafer, William M (2015) Future treatment of gonorrhea--novel emerging drugs are essential and in progress? Expert Opin Emerg Drugs 20:357-60
Bauer, Margaret E; Shafer, William M (2015) On the in vivo significance of bacterial resistance to antimicrobial peptides. Biochim Biophys Acta 1848:3101-11
Johnson, Paul J T; Shafer, William M (2015) The Transcriptional Repressor, MtrR, of the mtrCDE Efflux Pump Operon of Neisseria gonorrhoeae Can Also Serve as an Activator of ""off Target"" Gene (glnE) Expression. Antibiotics (Basel) 4:188-97
Unemo, Magnus; Golparian, Daniel; Shafer, William M (2014) Challenges with gonorrhea in the era of multi-drug and extensively drug resistance - are we on the right track? Expert Rev Anti Infect Ther 12:653-6
Cloward, Jason M; Shafer, William M (2013) MtrR control of a transcriptional regulatory pathway in Neisseria meningitidis that influences expression of a gene (nadA) encoding a vaccine candidate. PLoS One 8:e56097
Zalucki, Yaramah M; Dhulipala, Vijaya; Shafer, William M (2012) Dueling regulatory properties of a transcriptional activator (MtrA) and repressor (MtrR) that control efflux pump gene expression in Neisseria gonorrhoeae. MBio 3:e00446-12
Unemo, Magnus; Shafer, William M (2011) Antibiotic resistance in Neisseria gonorrhoeae: origin, evolution, and lessons learned for the future. Ann N Y Acad Sci 1230:E19-28
Ohneck, Elizabeth A; Zalucki, Yaramah M; Johnson, Paul J T et al. (2011) A novel mechanism of high-level, broad-spectrum antibiotic resistance caused by a single base pair change in Neisseria gonorrhoeae. MBio 2:
Kamal, Nazia; Shafer, William M (2010) Biologic activities of the TolC-like protein of Neisseria meningitidis as assessed by functional complementation in Escherichia coli. Antimicrob Agents Chemother 54:506-8

Showing the most recent 10 out of 71 publications