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Principal Investigator: William Maurice Shafer
Organization: VETERANS HEALTH ADMINISTRATION
Fiscal Year: 2024
Funding agency: Veterans Affairs
Project Summary
In this competitive renewal of my Senior Research Career Scientist (SRCS) award I will continue my research,
service, and teaching/mentoring efforts that have been the areas of concentration during past funding periods.
My research program focuses on antibiotic resistance as it is now recognized that the ability of bacterial
pathogens to evade the action of antibiotics is now one of the most important threats to worldwide public health.
My research program since entering the VA Medical Research service in 1987 has been to understand the
molecular basis by which bacteria develop resistance to antimicrobials with the ultimate goal of advancing basic
science knowledge to improving human health. As a model system, the laboratory has largely used the human
sexually transmitted pathogen Neisseria gonorrhoeae since this pathogen has historically developed resistance
to every antibiotic that has been brought into clinical practice and has a remarkable ability to avoid the action of
multiple host defense systems. Our research focus is of importance to both the veteran/active military and
civilian populations in the United States given that over 550,000 cases of gonorrhea are reported yearly with
over 50% of N. gonorrhoeae isolates resistant to one or more antibiotics. Moreover, the worldwide estimate of
cases approaches 100 million with reported instances of strains resistant to front-line antibiotics (azithromycin
and/or ceftriaxone). A major accomplishment of my laboratory has been the finding that mechanisms of
antibiotic resistance including multidrug efflux pumps, drug permeability changes due to alterations in
outer membrane structure and inner membrane homeostasis can be linked to the ability of gonococci to
evade mediators of host defense and survive during experimental infections. Thus, we advanced the
concept that antibiotic resistance and bacterial pathogenesis are not necessarily separate entities and should
be studied together. Importantly, our basic research efforts have now reached a point where translational-driven
efforts can facilitate vaccine development and new antibiotic discovery. In addition to these research efforts, I
have participated in and provided leadership for multiple local, national and international endeavors to combat
antibiotic resistance. These efforts include extensive peer-review service for journals and study sections,
membership on national and international advisory boards for agencies advancing new antibiotic development,
teaching/mentoring programs through directing an NIH-funded T32 program for pre-doctoral students,
developing and directing graduate level courses, and mentoring junior faculty at the Atlanta VA and Emory
University School of Medicine. These extensive efforts coupled with my ongoing productive research program
will be the focus of my SRCS-supported work during the next funding period.
Terms: <Antibiotic Agents><Antibiotic Drugs><Antibiotic Resistance><Antibiotic Therapy><Antibiotic Treatment><Antibiotics><Antimicrobial Resistance><Area><Armed Forces Personnel><Autoregulation><Award><Azadose><Azithromycin><Azitrocin><Azythromycin><Bacteria><Bacterial Antibiotic Resistance><Bacterial Infections><Basic Research><Basic Science><Biologic Models><Biological><Biological Models><Cefatriaxone><Cefixime><Ceftriaxone><Cephalosporins><Communicable Diseases><Communities><Country><Coupled><Dedications><Development><Disease><Disease Resistance><Disorder><Drug Efflux><Drugs><Education><Educational aspects><Educational process of instructing><Faculty><Female><Funding><Funding Agency><Funding Source><Generations><Goals><Gonococcal Infection><Gonococcus><Gonorrhea><Gynecologic><Health><Homeostasis><Host Defense><Human><Incidence><Infection><Infectious Agent><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><International><Journals><Knowledge><Laboratories><Leadership><Light><Link><Magazine><Mediator><Medical Research><Medication><Medicine><Membrane><Mentors><Military><Military Personnel><Miscellaneous Antibiotic><Model System><Modern Man><Molecular><Mucosa><Mucosal Tissue><Mucous Membrane><N gonorrhea><N gonorrhoeae><N. gonorrhea><N. gonorrhoeae><NIH><National Institutes of Health><Neisseria gonorrhea><Neisseria gonorrhoeae><Pathogenesis><Pathogenicity Factors><Peer Review><Permeability><Ph D student><Ph D. student><Ph. D. student><Ph.D student><Ph.D. student><PhD student><PhD. student><Pharmaceutical Preparations><Photoradiation><Physiological Homeostasis><Population><Postdoc><Postdoctoral Fellow><Predisposition><Productivity><Public Health><R Plasmids><Reporting><Research><Research Associate><Research Resources><Resistance><Resistance development><Resistance to antibiotics><Resistant development><Resistant to antibiotics><Resources><Science><Scientist><Sepsis><Services><Sexual Transmission><Sexually Transmitted Diseases><Sexually Transmitted Disorder><Sexually Transmitted Infection><Societies><Study Section><Surface><Susceptibility><System><Teaching><Transcription Regulation><Transcriptional Control><Transcriptional Regulation><Translational Research><Translational Science><Ultreon><United States><United States National Institutes of Health><Universities><Vaccines><Venereal Diseases><Venereal Disorders><Venereal Infections><Veterans><Virulence Factors><Work><Zithromax><Zitromax><anti-microbial><anti-microbial resistant><antibiotic drug resistance><antibiotic resistant><antibiotic resistant bacteria><antimicrobial><bacteria infection><bacteria pathogen><bacterial antibiotic resistant><bacterial disease><bacterial disease treatment><bacterial infectious disease treatment><bacterial pathogen><bacterial resistance to antibiotic><biologic><blood infection><bloodstream infection><career><career development><clinical practice><combat><develop a vaccine><develop vaccines><developing resistance><development of a vaccine><developmental><doctoral student><drug/agent><efflux pump><human pathogen><improved><infectious organism><male><medical college><medical schools><meeting><meetings><membrane structure><microbial><military population><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><new treatment approach><new treatment strategy><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapy approach><pathogen><pathogenic bacteria><post-doc><post-doctoral><post-doctoral trainee><pre-doc><pre-doctoral><predoctoral><programs><research associates><resistance factors><resistance strain><resistance to anti-microbial><resistance to disease><resistant><resistant disease><resistant strain><resistant to antimicrobial><resistant to disease><school of medicine><sexually acquired infection><sexually transmitted><student mentoring><student-led learning><therapeutic vaccine><translation research><translational investigation><translational study><treatment vaccines><vaccine development><vaccine for the treatment><vaccine for treatment>