M. tuberculosis Pathogenesis and Vaccine Development
Josephine Clark-Curtiss, PhD
Department: Medicine; Division of Infectious Diseases and Global Medicine
Research Interest: Tuberculosis, Mycobacterial parthenogenesis, Regulation of Gene Expression, Vaccines
Dr. Josephine Clark-Curtiss received her PhD in microbiology from the Medical College of Georgia in 1974. She joined the research group of Roy Curtiss III at the University of Alabama at Birmingham for postdoctoral studies in 1973 where she analyzed the genetic bases for transfer of antibiotic resistance (R) plasmids among enterobacteria and initiated molecular biology research in mycobacteria. She became a Research Assistant Professor in 1983 at the Washington University in St. Louis, MO, where she continued research on the pathogenesis and immune responses to Mycobacterium leprae. Later, she initiated studies on mechanisms of pathogenicity employed by Mycobacterium tuberculosis and M. avium, with particular emphasis on mycobacterial gene expression when the bacteria were growing in human macrophages in culture. In 2004, she joined the School of Life Sciences and the Center for Infectious Diseases and Vaccinology in The Biodesign Institute as a Professor at Arizona State University (ASU). Dr. Clark-Curtiss and her research group analyzed several different means that M. tuberculosis employs to regulate gene expression in response to different environments in which the bacteria survive and multiply. While at ASU, Dr. Clark-Curtiss’ group, in collaboration with Dr. Roy Curtiss’ group, made significant progress in developing a vaccine against M. tuberculosis.
She currently is a Professor in the Division of Infectious Diseases and Global Medicine at the University of Florida where she and her group are working to develop a safe, efficacious vaccine to protect humans against infections by M. tuberculosis, using recombinant, attenuated Salmonella vaccine (RASV) strains to deliver M. tuberculosis protective antigens. These endeavors involve collaborations between members of the Clark-Curtiss research group, who have expertise, experience and knowledge about M. tuberculosis and individuals in the Curtiss research group in the UF College of Veterinary Medicine, who have extensive expertise in developing and evaluating recombinant attenuated Salmonella vaccines and vaccine delivery systems. Dr. Clark-Curtiss’ interests in developing a tuberculosis vaccine stem from the belief that immunization to protect individuals from infection is superior to the continued development of new antibiotics to combat bacterial pathogens that inevitably acquire resistance to currently available or newly designed antibiotics.
The Clark-Curtiss research group is also working to understand mechanisms of tuberculosis pathogenesis through (a) analyses of M. tuberculosis gene expression, (b) identification of operational metabolic pathways during growth of the bacilli in human macrophages and dendritic cells and (c) analyses of regulation of gene expression. The team has identified M. tuberculosis genes that are expressed at different times after infection of cultured human macrophages, enabling them to identify metabolic pathways that are functional at those times. They have also characterized several classes of regulatory systems that control gene expression, both in vivo and in vitro. These include two-component regulatory systems, serine-threonine protein kinases, and toxin-anti-toxin regulatory modules. Knowledge gained from these research endeavors may aid vaccine development by identifying new candidate antigens to incorporate into the RASV-Mtb vaccines that will enhance protection in immunized individuals against infection by M. tuberculosis.