Understanding the molecular basis of fungal infections
Infectious diseases are one of the most challenging aspects of microbiology. Their toll on human health remains immense and emerging drug resistance puts us at risk of backsliding on a century of progress in treating these diseases. Fungi are often overlooked as infectious agents, despite causing a spectrum of diseases ranging from mild and common to life-threatening infections responsible for over one million deaths per year. Candida albicans is the most important fungal pathogen, as it is capable of infecting virtually any body site, including the mouth and throat (oral thrush) and the genital tract (vaginal yeast infections), but our primary interest is in the life threatening infections that occur mostly in hospitalized patients with weakened immune systems. Increasingly frequent, about 40% of those who get disseminated candidiasis will die, making it as deadly as HIV/AIDS and MRSA in this country. Unlike these infections, however, patients acquire candidiasis from themselves: C. albicans is also a universal part of the human microbiota, existing harmlessly in most of us.
Healthy individuals are protected from candidiasis by their innate immune system and our lab studies the dynamic and fascinating interaction of C. albicans with phagocytic cells. C. albicans dramatically alters macrophage function, by inhibiting production of antimicrobial compounds like nitric oxide and remodeling the phagolysosome, eventually allowing the fungal cell to adopt an filamentous morphology and escape the phagocyte. We seek to understand how this important pathogen has adapted its metabolism, stress responses, and physiology to contribute to its ability to cause disease, with an ultimate goal of identifying ways to better diagnose and treat these infections.
The dynamic interaction of Candida albicans with mammalian macrophages. C. albicans is stained in red, the macrophage actin cytoskeleton in green, and the macrophage nuclei in blue.
(Photo credit: Dr. Pedro Miramón)
Dr. Yasmin Chebaro
My first research experience in infectious diseases was studying M. tuberculosis at Texas A&M University, where I received my B.S. in Genetics. Afterward, I joined the Ph.D Program in Biochemistry and Cell Biology at Rice University, where I was a student in the laboratory of Dr. Michael Gustin. I then continued pursuing my interest in fungal infections by joining UT in August 2017, where I am currently focusing on Candida interactions with host immune cells.
Carrie E. Graham
As a collaboration between the Garsin Lab and Lorenz Lab, using different in vivo and in vitro models, I am investigating the interactions between Candida albicans and Enterococcus faecalis. E. faecalis and C. albicans occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species are also among the most important and problematic, opportunistic nosocomial pathogens. We have demonstrated antagonist interaction between C. albicans and E. faecalis, whereby a secreted bacterial factor inhibits hyphal growth in biofilms and in the Caenorhabditis elegans infection model, abrogating virulence. Using an in vitro biofilm model, I identified the secreted bacterial factor EntV, a putative bacteriocin, as both necessary and sufficient for the reduction of C. albicans virulence and biofilm formation through the inhibition of hyphal formation, a critical virulence trait. EntV is protective against C. albicans in a C. elegans infection model, murine macrophage infection model, and murine oropharyngeal candidiasis (OPC) model. Our findings demonstrate that EntV has potential as an antifungal agent that targets virulence rather than viability.
Dr. Pedro Miramón Martínez
I earned my Bachelor’s and Master’s degrees in Chemistry, Bacteriology and Parasitology at the Instituto Politécnico Nacional in Mexico City. After that, I was a Ph.D. student with Dr. Bernhard Hube at the Hans-Knoell-Institute and Friedrich Schiller University in Jena, Germany. I moved to UT in February, 2014, where I have continued to pursue my interest in the biology of fungal infections with a focus on the interaction of Candida species with phagocytic cells.
I am originally from Rio Rancho, NM, and earned a B.S. in Biology from New Mexico State University in 2012. My interest in research was encouraged by opportunities at NMSU as part of the BRAiN Research Program. Through this program I was able to experience a wide range of research disciplines before deciding to attend The University of Texas Health Sciences Center and join the Microbiology and Molecular Genetics program. My interests in Molecular Mycology and Infectious Disease lead me to the Lorenz Lab in May 2014. Since joining, I have been working on broadly understanding the molecular mechanisms required for C. albicans survival upon macrophage phagocytosis. I have shown that N-acetylglucosamine is a host-relevant carbon source that induces pH neutralization in a manner that is genetically independent from amino acids. Additionally, I am investigating several uncharacterized genes that are upregulated upon phagocytosis by primary murine macrophages.
I’m originally from Huntsville, Alabama, but moved to Houston after receiving a B.S. in Microbiology from Auburn University in 2015. I have always been fascinated by microbes and infectious diseases, but the research opportunities in the area were limited. Moving from a small town to the world’s largest medical center to pursue a PhD in the Lorenz Lab was an easy decision.
My current focus in the lab is to understand the adaptations that C. albicans undergoes to survive within macrophages. Our transcriptomic data suggests that utilization of carboxylic acids (lactate, pyruvate, etc.) is important for C. albicans interactions with macrophages, but this pathway is understudied. I hope to elucidate the mechanism by which carboxylic acid utilization confers fitness advantages.