Resistance to an entire class of antibiotics â€“ aminoglycosides — has the potential to spread to many types of bacteria, according to new biochemistry research.
A mobile gene called NpmA was discovered inÂ E. coliÂ bacteria isolated from a Japanese patient several years ago. Global spread of NpmA and related antibiotic resistance enzymes could disable an entire class of tools doctors use to fight serious or life-threatening infections.
Using X-ray crystallography, researchers at Emory made an atomic-scale snapshot of how the enzyme encoded by NpmA interacts with part of the ribosome, protein factories essential for all cells to function. NpmA imparts a tiny chemical change that makes the ribosome, and the bacteria, resistant to the drugsâ€™ effects.
The results, published in PNAS, provide clues to the threat NpmA poses, but also reveal potential targets to develop drugs that could overcome resistance from this group of enzymes.
First author of the paper is postdoctoral fellow Jack Dunkle, PhD. Co-senior authors are assistant professor of biochemistry Christine Dunham, PhD and associate professor of biochemistry Graeme Conn, PhD. Read more
If youâ€™re looking for an expert on the â€œnotoriousâ€ bacterium Clostridium difficile, consider Emory microbiologist Shonna McBride.
C. difficile is a prominent threat to public health, causing potential fatal cases of diarrheal disease. C. difficile can take over in someoneâ€™s intestines after antibiotics clear away other bacteria, making it dangerous for vulnerable patients in health care facilities. Healthcare-associated infections caused by other types of bacteria such as MRSA have been declining, leaving C. difficile as the most common cause, according to recently released data from the CDC.
Shonna McBride, PhD
McBrideâ€™s work focuses on how C. difficile is able to resist antimicrobial peptides produced by our bodies that keep other varieties of bacteria in check.
A 2013 paper from her lab defines genes that control C. difficile’s process for sequestering these peptides. It appears that its ability to resist host antimicrobial peptides evolved out of a system for resisting weapons other bacteria use against each other.
Since C. difficile requires an oxygen-free environment to grow, studying it can be more difficult than other bacteria. The McBride lab has a recent â€œvideo articleâ€ in the Journal of Visualized Experiments explaining how to do so using specialized equipment.
McBride explains in a recent Microbe magazine cover article that C. difficileâ€™s ability to form spores is connected to the threat it poses:
Without the ability to form spores, the strict anaerobe C. diffÄ±cile would quickly die in the presence of atmospheric oxygen. However, the intrinsic resilience of these spores makes them diffÄ±cult to eradicate, facilitating the spread of this pathogen to new hosts, particularly in health care settings where they withstand many of the most potent disinfectants.
Yet the process of sporulation is markedly different in C. difficile compared with other kinds of bacteria, she says in the review.