Investigating bacterial lipid metabolism, pathogenesis, and therapeutics development
Bacteria, specifically pathogens, present a clear and present danger in any hospital. Infectious disease management is critical to the success of therapies conducted in a health care environment. To advance effective infectious disease management, our laboratory studies major bacterial pathogens to develop an enhanced understanding of the host-bacteria interaction and how bacteria alter the host immune environment to favor their existence.
We examine how pathogens obtain nutrients, a mechanism which is an important aspect in the development of antibiotics that target these pathogens. Through the basic-science focus of our laboratory, we contribute to a deeper understanding of how pathogen-selective drugs can be developed and used in clinical settings.
Developing an effective therapeutic infectious disease response requires a robust comprehension of bacteria metabolism. Membrane formation is a vital aspect of bacterial lipid metabolism, and our goal is to understand these pathways to identify new targets for therapeutics development. Understanding how pathogens obtain lipid nutrients (fat) from the host is critical in determining the importance of lipid metabolism to infection.
We also study the intestinal microbiome and its diverse bacterial population to elucidate how these commensal bacteria use lipid metabolism to interact with the host in this distinctive environment. Our work seeks to examine the detailed aspects of biochemistry, molecular biology, structural biology, and genetics as we evolve our understanding of the communication between host and pathogen to guide the development of effective therapeutics.
Compound development and drug discovery
While we are a basic-science laboratory, the nature of our infectious disease research allows us to be heavily involved in drug discovery that translates directly to the clinic. Through our study of lipid metabolism in mammals—and an extensive collaboration with the Department of Chemical Biology and Therapeutics (CBT) and the Department of Structural Biology at St. Jude—we contribute to the development of compounds, such as chemical biology probes and drug-like molecules.
In a testament to the success of our collaborative work, one of our compounds has completed two Phase II trials, and recently, our work led to the application of the first-in-class drug treatments for childhood neurodegenerative and metabolic diseases. These molecules continue progress toward the clinic.
The commensal bacteria that exist in the intestine are not pathogenic, and the body’s immune system does not react to these organisms. This is due to extensive chemical cross-talk between the communal bacteria and host that suppresses the immune response and creates a more tolerant environment for the commensal bacteria. We identify hydroxy-fatty acids as one of the chemical-signaling molecules and examine the mechanism and regulation of their biosynthesis.
Importantly, we find that these same molecules are released by pathogens, such as Staphylococcus aureus, who have co-opted this aspect of commensal signaling to promote pathogenesis. We have also discovered two new lipid mediators produced by S. aureus that potentially activate or suppress components of the immune system.
These new molecules are being studied with our cutting-edge technologies that include anaerobic growth chambers and genetic knockouts of anaerobic bacteria, X-ray crystallography, mass spectrometry, NMR spectroscopy, and chemical biology. We continue to examine the distinctive lipid metabolites of intestinal microbiome bacteria and those of pathogens to provide insight into the role of lipid mediators in the control of inflammation and pathogenesis.
Victor J. Torres, PhD
Member, St. Jude Faculty
Chair, Department of Host-Microbe Interactions
Director, Center for Infectious Diseases Research
Albert and Rosemary Joseph Endowed Chair in Host-Microbe Interactions
St. Jude Children's Research Hospital