Update coming soon!
Dr. Abel-Santos is interested in research that combines the areas of organic chemistry, biochemistry and microbiology. Below are some of the current projects being studied in the Abel-Santos Lab:
Bacillus anthracis spore germination in macrophages
The Abel-Santos laboratory is currently applying enzymology approaches to the process of Bacillus spore germination. Due to its potential as a bioterrorism weapon, new methods to control B. anthracis (a.k.a ANTHRAX) infections are needed. B. anthracis spores are resistant to most type of antiseptic and antibiotic treatments. Although anthrax spores are resilient, they have to “taste” their environment to determine when conditions are right to germinate (e.g. your lungs) Using the information gathered from the kinetic models, we have developed nucleoside inhibitors against anthrax spore germination. These compounds have proven to be effective in protecting macrophage form anthrax-mediated killing.
B. anthracis life cycle upon macrophage phagocytosis
Clostridioides difficile prophylaxis and biological variables
Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea. Due to its insidious nature, the Centers for Disease Control and Prevention (CDC) has declared CDI an urgent threat. A key characteristic of C. difficile is its ability to form dormant spores that act as the infectious vehicles for disease. In the gut, spores recognize bile salts to germinate into toxin-producing cells.
Dysbiosis of the gut microbiome is a key factor in allowing the C. difficile spores to germinate. Normal gut microbiota naturally protects from CDI. However, biological variables such as diet and sex have been found to modulate to the gut microbiota. Antibiotics can also disrupt the natural microbiota within the gastrointestinal tract causing dysbiosis. Thus, antibiotic use in conjunction with biological variables may influence CDI outcomes. Since spore germination is a necessary step for CDI establishment, methods that target this process could prevent infection.
Under construction!
Paenibacillus larvae
Paenibacillus larvae, a Gram-positive bacterium, causes American foulbrood (AFB) in honey bee larvae (Apis mellifera Linnaeus [Hymenoptera: Apidae]). P. larvae spores exit dormancy in the gut of bee larvae, the germinated cells proliferate, and ultimately bacteremia kills the host. Hence, spore germination is a required step for establishing AFB disease. The Abel-Santos lab evaluates and identifies P. larvae spore germination inhibitors. We previously found that P. larvae spores germinate in response to l-tyrosine plus uric acid in vitro. Additionally, we determined that indole and phenol blocked spore germination. In more recent work, we evaluated the antagonistic effect of 35 indole and phenol analogs and identified strong inhibitors of P. larvae spore germination in vitro. We further tested the most promising candidate, 5-chloroindole, and found that it significantly reduced bacterial proliferation. Finally, feeding artificial worker jelly containing anti-germination compounds to AFB-exposed larvae significantly decreased AFB infection in laboratory-reared honey bee larvae. These results suggest that inhibitors of P. larvae spore germination could provide another method to control AFB.
P. larvae spore germination in the presence of 5-bromoindole and 5-chloroindole. (A) P. larvae spores were incubated with germinants and supplemented with 0 µM (open circle), 40 µM (filled circle), 80 µM (open square), and 200 µM (filled square) of 5-bromoindole. (B) P. larvae spores were incubated with germinants and supplemented with 0 µM (open circle), 20 µM (filled circle), 100 µM (open square), and 200 µM (filled square) of 5-chloroindole. Data are shown every 5 min for clarity. Spore germination was measured by a decrease in the relative OD over time. Error bars represent standard error obtained from at least six independent measurements. Figure was taken from Alvarado et al. 2017.
Batrachachytrium dendrobatidis
Batrachachytrium dendrobatidis (Bd) is the causative agent of the fatal skin disease in amphibians called chytridiomycosis, which has decimated amphibian populations across the globe. Bd has a two-stage lifecycle: It begins as a motile and flagellated zoospore, which then attaches to a surface and matures into a sessile phase called a zoosporangium, which in turn packages many new zoospores for release into the environment. However, very little has been studied in terms of the chemical or environmental factors that guides Bd’s progression through its lifecycle and the changes in gene expression that may occur under different conditions.
Image 2: Mixed population of zoospores and zoosporangia under normal growth conditions (H-broth: tryptone + glucose). We are interested in the environmental conditions necessary to get Bd to complete its life cycle and what kind of changes it undergoes as it does so.
Image 3: When grown on TGhL agar, we and others have noticed that the motile zoospores tend to stay close to the zoosporangia and within a visible and defined boundary. We are interested in the chemical signaling that may occur between zoosporangia and new zoospores that may explain this behavior.
Staphylococcus aureus
Staphylococcus aureus is a Gram-positive and grape-like shaped bacterium. It is an aerobic and facultative anaerobic bacterium, and unlike Clostridioides difficile, S. aureus is not a spore forming organism. S. aureus is an opportunistic and toxin releasing bacterium responsible for several types of diseases such as foodborne illness, endocarditis, pneumonia to name a few. The Abel-Santos Lab focuses on S. aureus and the gastrointestinal using a mouse model. Previous studies have shown that S. aureus causes antibiotic associated diarrhea. As the gut microbiota is depleted, S. aureus is able to colonize, release the toxin enterotoxin B and cause damage to the small intestine.
