Dr. Juan Martinez
Pathobiological Sciences (PBS)

Biography:
B.S in Microbiology U of I Ph.D. Microbial Pathogenesis Washington University Post-doc Institut Pasteur Paris, France

Teaching Interests:
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.

Research Interests:
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.

 Education:
  • PhD Washington University in St. Louis
  • BS The University of Illinois at Urbana-Champaign
 Grants:
  • The retropepsin-like enzyme RC1339/APRc from Rickettsiae as a potential therapeutic target for rickettsial disease, NIH/NIAID,
  • The roles of conserved outer-membrane proteins in SFG rickettsia pathogenesis, NIH/NIAID, $338,841.00
  • Molecular basis for spotted fever group Rickettsia vector competence in ticks, NIH/NIAID,
  • The roles of conserved outer-membrane proteins in SFG rickettsia pathogenesis, NIH/NIAID, $338,841.00
  • Molecular basis for spotted fever group Rickettsia vector competence in ticks, NIH/NIAID,
  • Center for Experimental Infectious Disease Research (COBRE) Phase III, NIHNIAID,
  • The roles of conserved outer-membrane proteins in SFG rickettsia pathogenesis, NIH/NIAID, $338,841.00
  • The roles of conserved outer-membrane proteins in SFG rickettsia pathogenesis, NIH/NIAID, $338,841.00
  • Evasion of complement-mediated killing by pathogenic rickettsial species, NIH/NIAID, $407,000.00
 Publications:
Journal Article, Academic Journal:
  • Evaluation of changes to the Rickettsia rickettsii transcriptome during mammalian infection., Riley, Sean; Pruneau, L; Martinez, Juan, 2017, PloS one , Volume: 12, Number: 8, Pages: e0182290
  • Expression of Rickettsia Adr2 protein in E. coli is sufficient to promote resistance to complement-mediated killing, but not adherence to mammalian cells., Garza, D; Riley, Sean; Martinez, Juan, 2017, PloS one , Volume: 12, Number: 6, Pages: e0179544
  • Engineering of obligate intracellular bacteria: progress, challenges and paradigms., McClure, E; Shaw, D; Carlyon, J; Ganta, R; Noh, S; Wood, D; Bavoil, P; Brayton, K; Martinez, Juan; McBride, J; Valdivia, R; Munderloh, U, 2017, Nature reviews. Microbiology
  • The <i>Rickettsia conorii</i> Adr1 Interacts with the C-Terminus of Human Vitronectin in a Salt-Sensitive Manner., Fish, A; Riley, Sean; Singh, B; Riesbeck, K; Martinez, Juan, 2017, Frontiers in cellular and infection microbiology , Volume: 7, Pages: 61
  • Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells., Curto, P; Simões, I; Riley, Sean; Martinez, Juan, 2016, Frontiers in cellular and infection microbiology , Volume: 6, Pages: 80
  • Nonselective Persistence of a Rickettsia conorii Extrachromosomal Plasmid during Mammalian Infection., Riley, S; Fish, A; Garza, D; Banajee, K; Harris, E; Del Piero, Fabio; Martinez, Juan, 2016, Infection and immunity , Volume: 84, Number: 3, Pages: 790-7
  • Electrotransformation and clonal isolation of Rickettsia species, Riley, Sean; Macaluso, Kevin; Martinez, Juan, 2015, Current Protocols in Microbiology , Volume: 39, Number: 3A.6, Pages: 1-20
  • Failure of a heterologous recombinant Sca5/OmpB protein-based vaccine to elicit effective protective immunity against Rickettsia rickettsii infections in C3H/HeN mice., Riley, S; Cardwell, M; Chan, Y; Pruneau, L; Del Piero, Fabio; Martinez, Juan, 2015, Pathogens and disease , Volume: 73, Number: 9, Pages: ftv101
  • Structure of RC1339/APRc from Rickettsia conorii, a retropepsin-like aspartic protease, Li, M; Gustchina, A; Cruz, Rui; Simoes, M; Curto, Pedro; Martinez, Juan; Faro, C; Simoes, Isaura; Wlodawer, Alexander, 2015, Acta Crystallografica D Biological Crystallography , Volume: 71, Number: Part 10, Pages: 2109-2118
  • RC1339/APRc from Rickettsia conorii is a novel aspartic protease with properties of retropepsin-like enzymes, Martinez, Juan; Riley, Sean; Simoes, Isaura; Cruz, Rui; Huegsen, Pitter; Wlodower, Alexander; Faro, Carlos; Overall, Christopher, 2014, PLoS Pathogens
  • Host-directed antimicrobial drugs with broad-spectrum efficacy against intracellular bacterial pathogens, Martinez, Juan; Czyz, Daniel; Potluri, Lakshmi; Gupta, Neeta; Riley, Sean; Steck, Theodore; Crosson, Sean; Shuman, Howard; Gabay, Joelle, 2014, mBio
  • Pathogenic Rickettsia species acquire vitronectin from human serum to promote resistance to complement mediated killing, Martinez, Juan; Riley, Sean; Patterson, Jennifer; Nava, Samantha, 2013, Cellular Microbiology , Volume: 16, Number: 6, Pages: 849-61
  • OmpA-mediated rickettsial adherence to and invasion of human endothelial cells is dependent upon interaction with α2β1 integrin., Hillman, Jr, R; Baktash, Y; Martinez, Juan, 2013, Cellular microbiology , Volume: 15, Number: 5, Pages: 727-41
  • Identification and characterization of the mammalian association and actin-nucleating domains in the Rickettsia conorii autotransporter protein, Sca2., Cardwell, M; Martinez, Juan, 2012, Cellular microbiology , Volume: 14, Number: 9, Pages: 1485-95
  • The rickettsial OmpB β-peptide of Rickettsia conorii is sufficient to facilitate factor H-mediated serum resistance., Riley, Sean; Patterson, J; Martinez, Juan, 2012, Infection and immunity , Volume: 80, Number: 8, Pages: 2735-43
  • Molecular basis of immunity to rickettsial infection conferred through outer membrane protein B., Chan, Y; Riley, Sean; Chen, E; Martinez, Juan, 2011, Infection and immunity , Volume: 79, Number: 6, Pages: 2303-13
  • Adherence to and invasion of host cells by spotted Fever group rickettsia species., Chan, Y; Riley, Sean; Martinez, Juan, 2010, Frontiers in microbiology , Volume: 1, Pages: 139
  • The Rickettsia conorii autotransporter protein Sca1 promotes adherence to nonphagocytic mammalian cells., Riley, Sean; Goh, K; Hermanas, T; Cardwell, M; Chan, Y; Martinez, Juan, 2010, Infection and immunity , Volume: 78, Number: 5, Pages: 1895-904