A Rough Start
Williams spent his formative years in the foster care system, from childhood until he landed a track scholarship to NCCU. Growing up on a farm, he worked hard as a young boy by harvesting tobacco, wheat and corn and learning to lay bricks. While his body was engaged in manual labor, Williams’ mind was engaged in the details of his surroundings — noticing the ponds and creeks and wondering what kind of life existed in them. “I’ve always been interested in figuring out how things work,” says Williams, who might still be laying brick if his high school masonry teacher hadn’t urged him to go to college. As an undergrad, Williams became more and more interested in science, but he still wasn’t sure if he wanted to do it for the rest of his life. So tested the waters by going for his master’s in biology. That trial morphed into a career, as Williams went on to a Ph.D. at N.C. State and then a postdoctoral fellowship at Emory University. It was there that he became intrigued by the topic of antibiotic resistance in bacteria. The mechanism of antibiotic resistance that Williams studied as a postdoc involved drug efflux pumps, tiny chemical mechanisms found in bacterial membranes that can recognize a broad range of antibiotics and pump them back out of the cell. But the gonorrhea bacteria has many additional ways of developing resistance to antibiotics. It can produce certain enzymes that render a drug ineffective. It can make changes in its own DNA called target-site modifications that mask the site on the microbe where the drug is supposed to attack. In fact, it seems like it can make any number of changes to its underlying DNA — through approaches called chromosomal-mediated resistance or plasmid-mediated resistance — to evade therapies. Recently, the World Health Organization issued a warning that gonorrhea has become so crafty that it may soon become untreatable. If left untreated, gonorrhea can spread to other organs, causing infertility, pelvic inflammatory disease, tubal pregnancy and damage to the joints and heart. “Eventually gonorrhea triggers an inflammatory response, causing tissue damage that gives the infection access to more nutrient-rich environments and allows it to spread throughout the bloodstream. The idea is to stop it before it gets to that point,” Williams says.
Microbial Resistance
Williams’ research identifies weaknesses in N. gonorrhoeae’s arsenal of resistance that others may be able to exploit in developing new therapies for the disease. His first studies upon joining the NCCU faculty in 2005 focused on
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Daniel williams
Associate Professor of Biology
the point of contact between the bacteria and the host cell. This contact — the initial step of infection — is made by little appendages on the bacterial surface called type IV pili. Williams has gone on to study how these structures work at the molecular level. He has also focused on another likely target of new drugs, the cell wall. Williams has discovered a molecule that coordinates a large-scale recycling effort to rescue and reuse pieces of the cell wall as the bacteria multiply and divide within the host. In the process, this master molecule appears to trigger the release of chemicals called cytotoxins, which then cause different types of inflammatory responses in the host — causing gonorrhea’s most severe complications. “That is where my research is heading, to look at what is happening from the perspective of the host cell,” Williams says. “How is the host cell responding to the infection, and can that response be tweaked to control the inflammation and its effects?”
Widening the Scope
Right now, Williams’ lab solely uses in vitro methods — meaning it looks at how the microbe acts in a test tube. He is reaching out to some of his mentors and colleagues — William Shaffer at Emory, Robert Nicholas at UNC–Chapel Hill and Antonio Baines at NCCU — to explore how the microbe behaves in cultured mammalian cells. “Even if I only contribute to the textbook knowledge on how gonorrhea works, for me that is just as important as
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“Even if I only contribute to the textbook knowledge on how gonorrhea works, for me that is just as important as the possible medical implications. But if along the way I find something that can improve medical care, that’s even better.”