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Rane H.S.,University of New Mexico | Hardison S.,South Texas Center for Emerging Infectious Diseases | Hardison S.,University of Texas at San Antonio | Botelho C.,University of Minho | And 6 more authors.
Virulence | Year: 2014

We have previously demonstrated that the C. albicans pre-vacuolar protein sorting gene VPS4 is required for extracellular secretion of the secreted aspartyl proteases Sap2p and Saps4-6p. Furthermore, the vps4Δ null mutant has been shown to be markedly hypovirulent in a murine tail vein model of disseminated candidiasis. In these experiments, we sought to further define the role of the pre-vacuolar secretion pathway mediated by the pre-vacuolar sorting gene VPS4 in the pathogenesis of epithelial and mucosal infection using a broad range of virulence models. The C. albicans vps4Δ mutant demonstrates reduced tolerance of cell wall stresses compared to its isogenic, complemented control strain. In an in vitro oral epithelial model (OEM) of tissue invasion, the vps4Δ mutant caused reduced tissue damage compared to controls. Further, the vps4Δ mutant was defective in macrophage killing in vitro, and was attenuated in virulence in an in vivo Caenorhabditis elegans model representative of intestinal epithelial infection. In contrast, the vps4Δ mutant caused a similar degree of tissue damage in an in vitro uroepithelial model of Candida infection compared with controls. Furthermore, in an in vivo murine model of vaginal candidiasis there was no reduction in fungal colony burden and no differences in vaginal histopathology compared to wild-type and complemented controls. These results suggest that VPS4 contributes to several key aspects of oral epithelial but not uroepithelial infection, and in contrast to systemic infection, plays no major role in the pathogenesis of Candida vaginitis. By using a wide range of virulence models, we demonstrate that C. albicans VPS4 contributes to virulence according to the specific tissue that is infected. Thus, in order to gain a full understanding of C. albicans virulence in relation to a particular gene or pathway of interest, a selected range of infection models may need to be utilized. © 2014 Taylor & Francis Group, LLC


News Article | December 1, 2016
Site: www.eurekalert.org

Charles Wilson, professor and Ewing Halsell Chair in Biology at The University of Texas at San Antonio (UTSA), has received an eight-year, grant from the U.S. Department of Health and Human Services expected to total $5,292,000. Wilson will receive the grant through the National Institutes of Health's (NIH) National Institute of Neurological Disorders and Stroke (NINDS), which aims to reduce the burden of neurological disease by supporting and conducting neuroscience research. Wilson's research focuses on the brain region involved in voluntary motor behavior, the basal ganglia. "This prestigious award from the U.S. Department of Health and Human Services is an immeasurable investment in brain health, which is a key research area not only for UTSA but also for the entire UT System. Dr. Wilson's research focus on the circuitry and function of neurons of the basal ganglia, which controls movement, will advance our understanding of degenerative disorders such Parkinson's disease. As a member of the UTSA Neurosciences Institute, Dr. Wilson is well deserving of this highly competitive NIH grant, and his top-tier research aligns with our Tier One goals," said Bernard Arulanandam, UTSA interim vice president for research. Wilson's research will examine local cell signaling in the basal ganglia to further develop a model of basal ganglia function. The goal of this modeling is to help improve current understanding of basal ganglia disorders and to assist in the development of potentially effective treatments. "With this substantial funding, UTSA will continue its leadership in brain health research and help the scientific community better understand, diagnose, treat and prevent neurological disorders like Parkinson's and Huntington's diseases. This work will help reduce folks' suffering and save lives," said U.S. Representative Joaquin Castro. "Thanks in large part to UTSA's impressive and expansive research programs, San Antonio is increasingly known as a city where science thrives. Our nation must never lose sight of the value of research, discovery, and knowledge. I'm proud that UTSA and the broader San Antonio community are leaders in learning, particularly in the field of brain health." The UTSA faculty includes 40 active researchers in brain health, an extensive initiative that includes research in neurodegenerative disease, traumatic brain injury, regenerative medicine, stem cell therapies, medicinal chemistry, neuroinflammation and drug design. This work is conducted across five top-tier research centers, including the UTSA Neurosciences Institute, the San Antonio Cellular Therapeutics Institute, the South Texas Center for Emerging Infectious Diseases, the Center for Innovative Drug Discovery and the Institute for Health Disparities Research. Leading the brain health revolution is one of UT System Chancellor William McRaven's "Quantum Leap" initiatives to provide the citizens of Texas the very best in higher education, research and health care. Chancellor McRaven has worked to make unprecedented investments in leveraging and connecting all the cutting edge science ongoing at UT institutions to drive collaboration and expand research efforts in brain health to meet a growing demand. The National Institute of Neurological Disorders and Stroke awarded the funding to UTSA through the Outstanding Investigator Award program. The program provides longer-term support to researchers whose records of achievement indicate their ability to make important contributions in the field of neuroscience. More stable grant funding gives recipients greater flexibility and freedom to conduct potentially groundbreaking research.


Yu X.,University of Texas at San Antonio | Korkmaz T.,University of Texas at San Antonio | Lilburn T.G.,Jamestown | Cai H.,University of Texas at San Antonio | And 3 more authors.
Proceedings - 2014 IEEE International Conference on Bioinformatics and Biomedicine, IEEE BIBM 2014 | Year: 2014

Malaria is one of the most deadly infectious diseases in the world. The malaria burden is characterized by 207 million cases and over 627,000 deaths annually. The consistent morbidity and mortality underscore an urgent need for the development of next-generation antimalarials. In this paper, we propose a network mining approach to uncover the protein-protein associations that are implicated in important cellular processes including DNA repair, genome integrity, transcriptional regulation, and pathogenesis. © 2014 IEEE.


Jupelli M.,South Texas Center for Emerging Infectious Diseases | Selby D.M.,Wilford Hall Medical Center | Guentzel M.N.,South Texas Center for Emerging Infectious Diseases | Chambers J.P.,South Texas Center for Emerging Infectious Diseases | And 4 more authors.
Journal of Interferon and Cytokine Research | Year: 2010

Neonatal Chlamydia trachomatis pneumonia has been associated with respiratory sequelae in later life. We recently established a mouse model of neonatal pulmonary Chlamydia muridaum infection and found an important contribution of IFN-γ to protective immunity. In this study, we further characterized the role of Th1-type cytokines; IL-12, IFN-γ, and IFN-γ signaling using mice genetically deficient in IL-12, IFN-γ, or IFN-γ receptor 1. All 3 knockout (KO) mice challenged intranasally with C. muridarum 1 day after birth exhibited 100% mortality by day 17 post-challenge whereas wild-type (WT) animals survived the monitoring period of 1 month. The KO mice exhibited greater lung bacterial burdens and enhanced dissemination to the liver, compared to WT animals. The inflammatory cellular infiltration in C. muridarum-challenged KO animals was significantly reduced in the lungs, but markedly enhanced in the livers of the KO mice compared to similarly challenged WT mice. It was also found that a deficiency in IL-12 or IFN-γ resulted in correspondingly reduced IFN-γ or IL-12 production, respectively, suggesting an intricate interdependence in the induction of these cytokines. Collectively, these results suggest that the IL-12/ IFN-γ axis induces pulmonary cellular infiltration, induces bacterial clearance from the lung, reduces dissemination to other organs, and promotes the survival of the host during neonatal pulmonary chlamydial infection. © Copyright 2010, Mary Ann Liebert, Inc.


Murthy A.K.,South Texas Center for Emerging Infectious Diseases | Chaganty B.K.R.,South Texas Center for Emerging Infectious Diseases | Troutman T.,South Texas Center for Emerging Infectious Diseases | Guentzel M.N.,South Texas Center for Emerging Infectious Diseases | And 6 more authors.
PLoS ONE | Year: 2011

The role of antigen-specific secretory IgA (SIgA) has been studied extensively, whereas there is a limited body of evidence regarding the contribution of non-specific SIgA to innate immune defenses against invading pathogens. In this study, we evaluated the effects of non-specific SIgA against infection with Vibrio cholerae O139 strain MO10 and biofilm formation. Seven day old infant mice deficient in IgA (IgA-/- mice) displayed significantly greater intestinal MO10 burden at 24 hr post-challenge when compared to IgA+/+ pups. Importantly, cross-fostering of IgA-/- pups with IgA+/+ nursing dams reversed the greater susceptibility to MO10 infection, suggesting a role for non-specific SIgA in protection against the infection. Since biofilm formation is associated with virulence of MO10, we further examined the role of human non-specific SIgA on this virulence phenotype of the pathogen. Human non-specific SIgA, in a dose-dependent fashion, significantly reduced the biofilm formation by MO10 without affecting the viability of the bacterium. Such an inhibitory effect was not induced by human serum IgA, IgG, or IgM, suggesting a role for the oligosaccharide-rich secretory component (SC) of SIgA. This was supported by the demonstration that SIgA treated with endoglycosidase H, to cleave the high-mannose containing terminal chitobiose residues, did not induce a reduction in biofilm formation by MO10. Furthermore, the addition of free mannose per se, across a wide dose range, induced significant reduction in MO10 biofilm formation. Collectively, these results suggest that mannose containing oligosacchardies within human non-specific secretory IgA can alter important virulence phenotypes of Vibrio cholerae such as biofilm formation, without affecting viability of the microorganism. Such effects may contribute significantly to innate immune defenses against invading pathogens in vivo in the gastrointestinal tract. © 2011 Murthy et al.


Montes M.,Interdisciplinary Graduate Program in Advanced Materials Engineering | Pierce C.G.,South Texas Center for Emerging Infectious Diseases | Lopez-Ribot J.L.,South Texas Center for Emerging Infectious Diseases | Bhalla A.S.,Interdisciplinary Graduate Program in Advanced Materials Engineering | And 3 more authors.
Journal of Nano Research | Year: 2016

Most microorganisms grow on surfaces as biofilms rather than as individual planktonic cells, and cells within biofilms show high levels of resistance against antimicrobial drugs. Thereby biofilm formation complicates treatment and contributes to high morbidity and mortality rates associated with infections. This study explores the physical, optical, and nano-structural properties of silver and copper nanoparticles dispersed in aqueous suspensions (nanoparticulate colloidal water) and examines their in vitro activity against microbial biofilms. Silver and copper nanoparticulate colloidal water of various concentrations were prepared and studied. Their surface energies, surface charge and surface plasmonic resonance properties were determined using contact angle measurement, zeta potential measurement and optical spectrometry, respectively. A model of biofilm formation on the wells of microtiter plates was used to determine the activity of the nanoparticulate suspensions against fungal and bacterial biofilms. Scanning electron microscopy (SEM) was used to observe the nanoparticle interactions with microbial cells within the biofilms. Results show that silver nanoparticle-containing liquids have higher surface energy than their copper counterparts; and that the surface energy increases as the concentration of silver nanoparticles increases. Altogether, the effectiveness of silver nanoparticle colloidal suspensions in controlling biofilm formation is observed and reported. For a given size of silver nanoparticles studied, it is found that the effective concentrations against microbial biofilms are far lower than their cytotoxic concentrations, indicating an overall safety and a good therapeutic index thus substantial application potential. © (2016) Trans Tech Publications, Switzerland.


Evani S.J.,University of Texas at San Antonio | Dallo S.F.,University of Texas at San Antonio | Ramasubramanian A.K.,University of Texas at San Antonio | Ramasubramanian A.K.,South Texas Center for Emerging Infectious Diseases
Frontiers in Microbiology | Year: 2016

Multiple studies support the hypothesis that infectious agents may be involved in the pathogenesis of atherosclerosis. Chlamydia pneumoniae is strongly implicated in atherosclerosis, but the precise role has been underestimated and poorly understood due to the complexity of the disease process. In this work, we test the hypothesis that C. pneumoniae-infected macrophages lodged in the subendothelial matrix contribute to atherogenesis through pro-inflammatory factors and by cell-matrix interactions. To test this hypothesis, we used a 3D infection model with freshly isolated PBMC infected with live C. pneumoniae and chlamydial antigens encapsulated in a collagen matrix, and analyzed the inflammatory responses over 7 days. We observed that infection significantly upregulates the secretion of cytokines TNF-α, IL-1β, IL-8, MCP-1, MMP, oxidative stress, transendothelial permeability, and LDL uptake. We also observed that infected macrophages form clusters, and substantially modify the microstructure and mechanical properties of the extracellular matrix to an atherogenic phenotype. Together, our data demonstrates that C. pneumoniae-infection drives a low-grade, sustained inflammation that may predispose in the transformation to atherosclerotic foci. © 2016 Evani, Dallo and Ramasubramanian.


PubMed | South Texas Center for Emerging Infectious Diseases
Type: Journal Article | Journal: PloS one | Year: 2011

The role of antigen-specific secretory IgA (SIgA) has been studied extensively, whereas there is a limited body of evidence regarding the contribution of non-specific SIgA to innate immune defenses against invading pathogens. In this study, we evaluated the effects of non-specific SIgA against infection with Vibrio cholerae O139 strain MO10 and biofilm formation. Seven day old infant mice deficient in IgA (IgA(-/-) mice) displayed significantly greater intestinal MO10 burden at 24 hr post-challenge when compared to IgA(+/+) pups. Importantly, cross-fostering of IgA(-/-) pups with IgA(+/+) nursing dams reversed the greater susceptibility to MO10 infection, suggesting a role for non-specific SIgA in protection against the infection. Since biofilm formation is associated with virulence of MO10, we further examined the role of human non-specific SIgA on this virulence phenotype of the pathogen. Human non-specific SIgA, in a dose-dependent fashion, significantly reduced the biofilm formation by MO10 without affecting the viability of the bacterium. Such an inhibitory effect was not induced by human serum IgA, IgG, or IgM, suggesting a role for the oligosaccharide-rich secretory component (SC) of SIgA. This was supported by the demonstration that SIgA treated with endoglycosidase H, to cleave the high-mannose containing terminal chitobiose residues, did not induce a reduction in biofilm formation by MO10. Furthermore, the addition of free mannose per se, across a wide dose range, induced significant reduction in MO10 biofilm formation. Collectively, these results suggest that mannose containing oligosaccharides within human non-specific secretory IgA can alter important virulence phenotypes of Vibrio cholerae such as biofilm formation, without affecting viability of the microorganism. Such effects may contribute significantly to innate immune defenses against invading pathogens in vivo in the gastrointestinal tract.

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