James E. Bina, PhD
- Post Doctoral Training, Department of Microbiology and Immunobiology, Harvard Medical School
- PhD, University of British Columbia
- MSc, BSc, University of Wisconsin, Madison
Associate Professor, Department of Microbiology and Molecular Genetics
Member, Graduate Program in Microbiology and Immunology (PMI)
The Bina lab studies antimicrobial resistance and bacterial pathogenesis in the gram-negative pathogens Vibrio cholerae and Klebsiella pneumoniae. The log-term goal of our studies are to define the mechanisms that bacteria use to cause human disease and to develop novel therapeutic approaches to circumvent antibiotic resistance.
The major focus of the lab is on V. cholerae which is an aquatic organism that causes the epidemic diarrheal disease cholera. Cholera affects ~5 million people each year, primarily in developing regions of the world. A major focus of our lab is to elucidate the function of RND-family multidrug efflux systems in bacterial biology. RND systems are ubiquitous transporters in gram negative bacteria that provide cross-resistance to multiple antimicrobials. This makes them crucial for the development of antibiotic resistance. However, the native functions of the RND systems are unknown. We have shown that the RND systems are required for V. cholerae pathogenesis. Mutation of the RND systems results in cells that are no longer able to express virulence genes or persist in the host gastrointestinal tract. These findings validated the RND systems as novel targets for the development of antivirulence and antimicrobial therapeutics. Ongoing work is focused on characterizing the molecular mechanisms that link efflux to V. cholerae biology and identifying novel inhibitors of the RND efflux systems.
Recently we expanded our studies to Klebsiella pneumoniae. K. pneumoniae is an understudied gram-negative pathogen that causes a multitude of healthcare-associated infections including pneumonia, bloodstream infections, urinary tract infections, wound or surgical site infections, and meningitis. K. pneumoniae has rapidly evolved resistance to all clinically relevant antibiotics which has landed it on the priority 1 list of pathogens published by the World Health Organization. We are working to define and characterize the intrinsic mechanisms that allow K. pneumoniae to resist antibiotics and persist in humans during infection.
Bina XR, Howard MF, Taylor DL, Ante VM, Kunkle DE and Bina JE. 2018. The Vibrio cholerae RND efflux systems impact virulence factor production and adaptive responses via periplasmic sensor proteins. PLoS Pathog. 14: e1006804.
Kunkle DE, Bina XR, Bina and Bina JE. 2017. The Vibrio cholerae VexGH RND Efflux System Maintains Cellular Homeostasis by Effluxing Vibriobactin. mBio. 8.
Bina, XR, Howard MF, Ante VM and Bina JE. 2016. Vibrio cholerae LeuO links the ToxR regulon to the expression of lipid A remodeling genes. Infection & Immunity. 84: 3161-3171.
Bina XR, Taylor DL, Vikram A, Ante VM and Bina JE. 2013. Vibrio cholerae ToxR downregulates virulence factor production in response to cyclo(Phe-Pro). mBio. 4: e00366-13.
Ante VM, Bina XR, Howard MF, Sayeed S, Taylor DL and Bina JE. 2015. Vibrio cholerae leuO Transcription Is Positively Regulated by ToxR and Contributes to Bile Resistance. Journal of Bacteriology. 197: 3499-3510.