Anthony Gaca

Award

  • 2010 - Mellville A. Hare Award for Excellence in Teaching

Bio

Anthony graduated from Michigan State University in 2008 with a Bachelors of Photo of Anthony GacaScience degree in Microbiology. While attending MSU he worked as a research assistant in the laboratory of Dr. James Tiedje identifying and characterizing novel bacterial isolates able to utilize phenolic pollutants as carbon sources. In the fall of 2008, Anthony was admitted into the IMV PhD program at the University of Rochester. In 2009, he joined the laboratory of Dr. José Lemos to begin his thesis work studying stress responses in the nosocomial pathogen Enterococcus faecalis. During his time in the IMV program, Anthony received the Mellville A. Hare Award for Excellence in Teaching for his time training undergraduates in introductory microbiology lab. Anthony was also awarded a travel grant to give an oral presentation about his research at the 4th International ASM Conference on Enterococci. In addition to his research, he is actively involved in the PhD candidate recruitment process for the IMV program.

Research Description

Enterococcus faecalis is a common gastrointestinal inhabitant of humans and is generally regarded as a harmless commensal in immunocompetent individuals. However, the human gastrointestinal tract imposes many environmental and chemical stresses on the microbiota that resides there. As a result, E. faecalis is a resilient organism capable of tolerating large fluctuations in environmental conditions and exposure to antibiotics making this organism particularly well adapted to survive and spread in a hospital setting. In order to cope with this dynamic environment, E. faecalis possess numerous regulatory mechanisms that mediate physiologic alterations to prime the cell for survival under harsh conditions. One of these regulatory mechanisms is the stringent response. The stringent response is a global stress response mechanism that is conserved among bacteria and is mediated by the accumulation of a unique pyrophosporylated form of guanisine triphospahte (GTP) called (p)ppGpp. This response is characterized by down-regulation of genes associated with the translation apparatus and up-regulation of genes involved in amino acid biosynthesis and stress survival.

Anthony’s research focuses on elucidating both the physiological significance of (p)ppGpp in the stress tolerance and virulence of E. faecalis, but also defining the biochemical pathways through which (p)ppGpp exerts its control over cellular metabolism. In E. faecalis, (p)ppGpp is synthesized by two enzymes; the bifunctional synthetase/hydrolase RelA and the weak synthetase RelQ. The (p)ppGpp profiles of ΔrelA, ΔrelQ, and ΔrelAQ deletion strains revealed that RelA is the primary enzyme responsible for (p)ppGpp synthesis during stress conditions, while RelQ appears to maintain basal levels of (p)ppGpp during favorable growth conditions. Physiological characterization of ?rel strains revealed that a high basal level of (p)ppGpp, characteristic of ?relA, corresponded with enhanced tolerance toward antibiotics that inhibit cell wall synthesis. A complete lack of (p)ppGpp, as seen in ?relAQ, led to overall decreased antibiotic tolerance and attenuated virulence in vivo. Together, these findings strongly suggest that (p)ppGpp pools have a crucial role in mediating stress tolerance and virulence in E. faecalis.

Articles Published

  1. de Oliveira NE, Abranches J, Gaca AO, Laport MS, Damaso CR, Bastos Mdo C, Lemos JA, Giambiagi-deMarval M. (2011). clpB, a class III heat-shock gene regulated by CtsR, is involved in thermotolerance and virulence of Enterococcus faecalis. Microbiology. 157:656-65.

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