Dr. Juan Martinez
Pathobiological Sciences (PBS)
B.S in Microbiology U of I
Ph.D. Microbial Pathogenesis Washington University
Post-doc Institut Pasteur Paris, France
I am currently involved in teaching of the didactic course VMED 5130 - BACTERIOLOGY AND MYCOLOGY. I am also interested in promoting the teaching of mechanisms of bacterial pathogenesis to students at the graduate (Ph.D.) level.
The Gram-negative α-proteobacteria of the genus Rickettsia are small (0.3-0.5 x 0.8-1.0 μm), obligate intracellular organisms. They are categorized into two major groups, the Spotted Fever Group (SFG) and Typhus Group (TG), which can be distinguished by antigenicity and intracellular actin-based motility. Members of this genus are responsible for severe human diseases and several species including R. conorii, R. rickettsii, R. prowazekii, and R. typhi, have been classified as Category B and C Priority Pathogens by the National Institute of Allergy and Infectious Diseases (NIAID) for their potential use as tools for biological terrorism.
Adhesin-receptor pairs involved in pathogenesis
The pathogenesis SFG rickettsia, upon transmission into the host, depends on the pathogen’s ability to bind to and invade target host cells. Although endothelial cells are the primary target cells in the host, many non-endothelial cell lines can also be efficiently invaded by rickettsial strains, suggesting that either multiple receptors govern host cell interactions or that a putative receptor is ubiquitously expressed in many cell types. Analysis of several completed rickettsial genomes has revealed the presence of at least 17 open reading frames (orfs) termed sca (surface cell antigens) whose putative products exhibit high homology to auto-transporter protein families in Gram-negative bacteria. Five members of this family, Sca0, Sca1, Sca2, Sca4 and Sca5 are highly conserved among most pathogenic SFG rickettsia. Interestingly, rOmpA (Sca0) and rOmpB (Sca5) have both been shown to be involved in rickettsial adherence and invasion into normally non-phagocytic mammalian cells; however, very little is known about the function of other conserved Sca proteins in pathogenesis. Research in the lab is focused on addressing the following research interests:
a) Elucidation of the roles of conserved Sca proteins from R. conorii and R. rickettsii in the interaction with endothelial cells; b), Identification of mammalian receptors for SFG rickettsiae; c) Generation of protective humoral immune responses against SFG rickettsiae using established murine models of infection.
Serum resistance as a novel virulence mechanism for rickettsial species
We have recently determined that in the absence of neutralizing antibodies, a model SFG rickettsial species R. conorii is able to evade complement-mediated killing in human and murine serum. These results suggested that R. conorii and other rickettsial species likely have evolved active mechanisms to evade the bactericidal effects of complement deposition as the pathogen disseminates in the bloodstream to target organs and tissues. We have identified at least two rickettsial antigens that are sufficient to mediate survival in normal murine and human serum. Interestingly, homologues to these antigens exist in all pathogenic rickettsiae suggesting that the ability to actively perturb complement-mediated killing in the blood is a novel virulence attribute for this class of pathogens. My lab is currently pursuing the following avenues of research:
a) The contribution of conserved rickettsial antigens to resistance to complement-mediated killing in mammalian blood; b) Generation of targeted mutants in rickettsial species and the characterization of these mutants using in vivo, in vitro and ex-vivo models of infection; c) Generation of protective immunity (both active and passive) using recombinant purified rickettsial antigens and antibodies, respectively.