An enzyme that makes pandemic cholera resistant to last-line antibiotics acts on a different mechanism than similar proteins in bacteria, researchers at the University of Georgia reported last month.
Cationic antimicrobial peptides (CAMPs), which naturally produced by both bacteria and human immune systems, are synthesized into last-line drugs. By chemically disguising the cell walls of bacteria, however, cholera strains can prevent CAMPs from binding to the cell wall of bacterium, achieving last-line drug resistance.
A team of researchers at the University Georgia previously discovered that three proteins are involved in the modification process and clearly defined the roles of two proteins. The new study, which was published in December, outlines the function of the third protein, the enzyme AlmG, in modifying the cell wall.
“It became apparent over the course of our work that how (this enzyme) improves shield functionality is quite different than would be expected based on what we know about groups of enzymes that look similar,” Jeremy Henderson, a former University of Georgia graduate student, said.
Henderson led the research into how AlmG attaches glycine, a small amino acid, to lipid A, a component of the bacterium cell’s outer membrane. The modification prevents CAMPs from binding to the outer walls of bacteria by changing the charge of lipid A molecules. AlmG’s mechanism for administering the modification is different than other enzymes that modify lipid A, researchers found.
“The level of protection conferred by this particular modification in Vibrio cholerae puts it in a league of its own,” Henderson said.
Additionally, because gene encoding determining antibiotic resistance can spread to different types of bacteria, last-line antibiotic resistance in the El Tor family of Vibrio cholerae could jump to bacteria that are already resistant to first-line antibiotics, researchers warn.