Prior to my retirement in 2023, research in my laboratory focused on the genetic and biochemical characterization of gene regulation and specialized recombination systems in S. Typhimurium, E. coli, Acinetobacter baylyi, Neisseria meningitidis, N. gonorrhoeae, Moraxella lacunata, and Pseudoalteromonas atlantica.

Jorge C. Escalante-Semerena, Ph.D.

Research Interests

Bacteria have existed on Earth for approximately four billion years and have fully colonized our planet, including places where animals and plants cannot survive due to the lack of oxygen or extremely high temperatures. Animals (including humans) and plants are embedded in this bacterial world. We know that the human body hosts an extraordinarily large number of bacteria (nine out of every ten cells in our body are bacteria), and that our own health hinges on mutually beneficial interactions with our guests. Similarly, plants depend on bacteria and other microorganisms found in the soil for the nutrients they need to survive. Now, more than ever, a better understanding of the strategies used by bacteria to survive in vastly diverse environments will help us solve many problems afflicting humankind.

My research group seeks to understand how bacterial cells work. Because of their relative simplicity, bacteria offer unique opportunities to study the processes that support life. Microbiologists play a critical role in the generation of new knowledge that can help us address societal challenges such as the deterioration of environment, the need to alleviate human and animal suffering caused by existing and emerging infectious diseases, the production of alternative energy sources, etc. Such new knowledge often translates into practical applications. In the absence of a constant stream of ideas generated by basic science, progress stalls.

Research universities are unique settings where connections between basic and applied scientists flourish. In the field of microbiology, this connectivity is greatly enhanced as a function of the breadth and depth of the areas of microbiology represented within a university. The University of Georgia is amongst a handful of institutions in the USA that offers such diversity in the microbial sciences. 

My research group uses bacteria to reveal how cells work. We seek answers to questions that apply to all cells, such as…

• How do cells cope with exogenous and endogenous metabolic challenges? The impact that stimuli have on the functionality of the cell can be profound. Because bacteria are single-cell forms of life, they are particularly susceptible to the negative effects caused by profound changes in metabolism, and thus must respond to such challenges rapidly and effectively.

In 1998, we discovered in bacteria a reversible system that regulates major cellular processes. Such a system  was previously thought to be unique to more complex forms of life, such as the human cell. Our discoveries were particularly relevant to the field of human cell aging, a poorly understood field of research. Given that the alluded control system is conserved in all forms of life, new knowledge acquired through our work with bacteria improved our understanding of why we get old and allow us to imagine ways to slow down the aging process.

• How do cells avoid the toxic effects of some chemicals? Our work in this research area centers on how bacteria that live in the soil or the gut of mammals make a living by consuming compounds that can harm plants and animals. This is one example of the many benefits humans get from bacteria living in the intestine. That is, even when we eat such hazardous compounds, our gut bacteria promptly consume them protecting us from their harmful effects. Notably, many of these compounds are used by the food industry as preservatives because they kill food-spoiling bacteria. Amazingly, we do not understand how these compounds kill cells. Knowledge gained from our work in this area may shed light on potentially new antimicrobial strategies.

• How do cells make complex molecules that are essential nutrients for humans? For over two decades, we have investigated how bacteria make coenzyme B12, an essential human coenzyme made only by bacteria. In humans, coenzyme B12 deficiencies cause serious health problems and even death. Humans get their B12 from their diet and from bacteria in their gut. Gut health-promoting bacteria are marketed to the American public as probiotics, which are typically consumed in yogurt-type dairy products. A better understanding of the role of B12 in the physiology of these microorganisms might lead to improved strains of probiotics. B12 is also important to diarrhea-causing bacteria, such as those that have recently caused outbreaks of food poisoning in the USA and cholera, which is a devastating intestinal disease common in the underdeveloped world. The survival of many of these disease-causing organisms depends on their ability to make and use coenzyme B12. Consequently, research in our lab on how B12 is made has identified potential targets for the design of antibiotics that could kill the bacteria without having side effects on humans. Lessons learned through years of work on B12 synthesis allowed us examine the possible use of B12 as an anti-cancer drug delivery vehicle. The results of initial studies are promising and justify further exploration of the use of B12 in this important area of human health care.

The Dailey lab’s research focuses on the enzymes responsible for heme biosynthesis. 

Work in my lab focuses on flagellar biosynthesis in Helicobacter pylori, a bacterium that colonizes the human stomach where it can cause a variety of stomach diseases including chronic gastritis, peptic ulcer disease and gastric cancer. Flagellum-mediated motility is essential for H. pylori to colonize the gastric mucosa. Understanding flagellar biosynthesis in H. pylori may lead to new strategies for controlling infections of this significant human pathogen.  H. pylori cells typically possess two to six sheathed flagella at one cell pole.  Using H. pylori as a model, we study mechanisms that control transcription of the flagellar genes, localization of the flagella to the cell pole, and the number of flagella.  The membrane sheath that surrounds the H. pylori flagellum is contiguous with the outer membrane, and we study the biosynthesis of the flagellar sheath.

In a separate project, we study the role of a 5-methylcytosine (m5C) DNA methyltransferase (MTase) in H. pylori.  H. pylori genomes are remarkable for the large number of DNA MTases they possess.  Most H. pylori DNA MTases are part of restriction-modification systems, although some are ‘orphans’ that do not have associated restriction enzymes.  M.HpyAVIII is a 5-methylcytosine (m5C) MTase that recognizes the motif 5’-GCGC-3’ and is an orphan MTase in most H. pylori strains.  Disrupting the gene encoding M.HpyAVIII in some H. pylori strains results in no distinctive phenotype, while in other strains loss of M.HpyAVIII severely impairs the growth rate.  Current work in the lab focuses on understanding the role of M.HpyAVIII in global gene expression in various H. pylori strains, as well as identifying alleles that are responsible for the slow growth of the M.HpyAVIII mutant strains.  The information generated in the proposed studies will allow us to develop rules to predict which 5mC sites impact transcription, which will have a broad impact on understanding the roles of m5C MTases in H. pylori and other bacteria.

Figure 1. Transmission electron microscopy (TEM) image of a wild-type H. pylori cell. The cluster of flagella at one of the cell poles.  Image taken by Dr. Jennifer Tsang in the Hoover lab.

Figure 2. TEM image of a H. pylori fliA mutant.  FliA is an alternative sigma factor required for transcription of genes whose products are required late in flagellar assembly. The bacterium is undergoing cytokinesis and has truncated flagella the cell poles. Image taken by Dr. Jennifer Tsang in the Hoover lab.

My research focuses on host-microbe interactions and bacterial cell-cell signaling; however, my interests in the field of Microbiology are broad and encompass bacterial genetics and physiology, among other topics.  My lab studies the light-organ symbiosis between the bioluminescent bacterium Vibrio fischeri and the squid Euprymna scolopes, as a model for natural bacteria-animal interactions.  Research topics are described on the Stabb lab web page and include:

• Pheromone-mediated regulation in V. fischeri

• Interspecies signaling and recognition of V. fischeri by the host

• Physiology and genetic regulation in symbiotic V. fischeri cells

• Developing genetic and genomic tools for V. fischeri and other members of the Vibrionaceae

You can find most of my publications in PubMed or Google Scholar.