NEW CHEMICALS MAY FIGHT SOME KINDS OF DRUG-RESISTANT BACTERIA
COLUMBUS, Ohio -- An Ohio State University researcher has helped discover chemicals that may prevent bacteria from developing resistance to an important class of antibiotics.
Drugs based on these chemicals may one day keep new strains of antibiotic-resistant bacteria under control.
Yen-ho Chu, assistant professor of chemistry at Ohio State, leads a team of researchers who are working to prevent bacterial resistance to a particular group of antibiotics called vancomycins.
"Vancomycins are among the last class of antibiotics physicians can prescribe to treat bacterial infections," Chu said. "Today, many bacteria are resistant to penicillin-based antibiotics. Vancomycin-resistant bacteria arent that prevalent right now, but they will be a huge problem very soon."
According to the Centers for Disease Control and Prevention, in 1989, 0.4 percent of intensive-care unit patients who acquired bacterial infections during their stay in U.S. hospitals
demonstrated a resistance to vancomycin. Four years later, that number swelled to 13.6 percent.
Bacteria become drug-resistant when people overuse antibiotics or dont finish a full antibiotic course. Over time, the bacteria mutate to survive, usually by releasing a new protein or enzyme to counteract a particular antibiotic.
Such is the case with bacteria that develop resistance to vancomycin, a drug which normally kills bacteria by binding to the chemical that builds bacterial cell walls. "Vancomycin causes new bacteria to form with fragile walls," Chu said. "Later, the walls break, and the bacteria die."
Bacteria become vancomycin-resistant by secreting an enzyme researchers call VanX. This enzyme shuts off the chemical reaction pathway that bacteria normally use to create cell walls. These resistant bacteria also initiate a new pathway -- one that builds cell walls with a different chemical that vancomycin cant recognize.
Chu and his partners, Ray Bakhtiar, a scientist at Merck & Co., Inc., and Christopher T. Walsh, a professor at Harvard Medical School, presented a possible solution to this problem on April 15 in San Francisco at the national meeting of the American Chemical Society.
To keep bacteria from becoming vancomycin-resistant, Chu and his colleagues sought a chemical analogue, a substance that would bind with VanX and keep the new reaction from taking place. The researchers turned to combinatorial chemistry, a technique that lets them create millions of compounds at the same time and screen for the ones that are pharmaceutically active.
"Essentially, combinatorial screening is like ocean fishing," Chu said. "We screened hundreds of compounds, and we fished out three that we could use to construct analogues. These analogues arent drugs yet, but theyre a start. Scientists can analyze them and one day make drugs."
Drugs based on VanX analogues would force bacteria to remain vulnerable to vancomycin, so the antibiotic would continue to be effective. Physicians would prescribe combination therapy -- a vancomycin antibiotic plus a VanX inhibitor -- for patients with vancomycin-resistant infections, a procedure that resembles AIDS treatment today.
In the future, Chu and his colleagues will expand their work. "So far, weve shown that these analogues inhibit the VanX enzyme in test tubes," Chu said. "Now we want to see if we can synthesize even better analogues, and then test them on bacteria."
Contact: Yen-Ho Chu, (614) 688-4079; Chu@chemistry.ohio-state.edu
Written by Pam Frost, (614) 292-9475; Frost.18@osu.edu