Research | Publications | Lab Members | Biosketch (Pdf format)
Carlos J. Orihuela, Ph.D.
STRF - Room 289.1
Tel: (210) 562-4192
Fax: (210) 562-4191Email:
For 18 years my research focus has been the host-pathogen interactions responsible for the development of invasive Streptococcus pneumoniae infections. S. pneumoniae is a leading cause of community-acquired pneumonia, sepsis, and meningitis (Fig 1). In my laboratory we routinely use isogenic deletion mutants of S. pneumoniae, knockout mice, and advanced molecular techniques to identify the host and bacterial factors that modulate disease progression and investigate the innate immune response to this important pathogen.
Pneumococcal serine-rich repeat protein (PsrP) (Fig. 2): In 2001 we determined that the genetic locus encoding PsrP was a S. pneumoniae pathogenicity island. Since then we have shown that mutants deficient in psrP are attenuated in the lungs but not the bloodstream of experimentally infected mice, PsrP binds to Keratin 10 on lung epithelial cells, PsrP promotes a homophilic interaction with PsrP on other pneumococci that promotes in vivo biofilm formation, and PsrP is a protective vaccine antigen. PsrP is a member of the glycosylated Serine-rich repeats protein family. We are currently exploring how PsrP glycosylation impacts its function.
Biofilm formation during colonization: In sharp contrast to the robust, even excessive, inflammatory response to S. pneumoniae in the lungs, nasopharyngeal colonization by this bacterium is characterized by the absence of an overt pro-inflammatory response. Over the past 4 years have shown that S. pneumoniae forms biofilms within the nasopharynx and that pneumococci within these biofilms are non-invasive and immunoquiescent. Current studies are focused on how the biofilm phenotype modulates the host immune response.
Age-associated inflammation enhances susceptibility to pneumonia (Fig. 3). We have determined that the chronic low-grade inflammation associated with aging contributes to the enhanced susceptibility of the elderly to pneumococcal pneumonia. This occurs as a result of increased expression of proteins that are co-opted by S. pneumoniae for lung cell adhesion and tissue invasion. Sterile chronic inflammation also triggers a homeostatic response in macrophages that suppresses their ability to respond to invading bacteria. We are currently examining the molecular signaling pathways involved in age-dependent macrophage dysfunction.
Cardiotoxicity during invasive pneumococcal disease. This is our newest are of research. We are exploring whether and how S. pneumoniae had direct cardiotoxic properties. Considerable epidemiological data supports this notion with ~20% of individuals who are hospitalized for pneumococcal pneumonia experiencing an adverse cardiac event, and those that recover from infection being at elevated risk for cardiac-related death for up to 1-year post infection.
2011 Presidential Junior Research Scholar Award, UTHSCSA
2011 Glenn Award for Research in Biological Mechanisms of Aging
2011 Distinguished Hispanic Faculty from the Graduate School of Biomedical Sciences, UTHSCSA
2012 - present Permanent member NIH CSR Aging Systems and Gerontology Study Section
2012 - present PLOS Pathogens Associate editor
2001-present American Society for Microbiology
2001-present Society for Advancement of Chicanos and Native Americans in Science
2006-present Barshop Institute for Longevity and Aging Studies, UTHSCSA
2008-present American Thoracic Society
2012-present Center for Airway Inflammation Research, UTHSCSA
2013-present Society for Leukocyte Biology
For more publications, please click on link NCBI.NLM.NIH.gov
Lab Rooms: STRF - 275.1 A-F Phone: (210) 562-4172