The Structures and mechanisms That Enables Bacteria Resist Antibiotics

This is a ribbon diagram of the three-part efflux pump of the Campylobacter jejuni bacterium. Credit: Edward Yu/Iowa State University

..[Yu's] research group have just described two structures and mechanisms -- efflux pumps and reinforced cell walls -- that certain disease-causing bacteria use to keep antibiotics away. That understanding could one day lead to new treatments that disable the structures and restore the effectiveness of drugs.

We study a lot of efflux pumps to understand antibiotic resistance...Cell wall remodelling is also a major mechanism to work against antibacterial drugs.

Two journals have just published the latest findings by Yu's research group:

A paper published online by Nature Communications describes how the Campylobacter jejuni bacterium, which causes a digestive tract inflammation (enterocolitis) and associated diarrhoea, uses a three-molecule efflux pump to extrude antibacterial drugs.

Previous studies reported the three molecules of the pump worked in a synchronized rotation -- one molecule accessing, one molecule binding and one molecule extruding -- to pump antibiotics from the cell. Yu's research group found that each part of the pump worked independently of the others, essentially creating three pumps in one structure.

A paper published online in the Proceedings of the National Academy of Sciences Early Edition describes how the Burkholderia multivorans bacterium, which can cause pneumonia in people with immune deficiencies or lung diseases such as cystic fibrosis, is able to remodel and strengthen its cell wall, closing the door to a range of antimicrobial drugs. Kumar and Su are first authors.

The paper focuses on how these bacteria transport hopanoid lipid compounds to their outer cell membranes. The compounds contribute to membrane stability and stiffness.

With that comprehensive understanding of the structures and mechanisms behind bacterial resistance to antibiotics, Yu said his research group is beginning to look at how the pumps and transporters can be turned off.

"We're trying to find an inhibitor compound," Yu said. "We're thinking about doing a little more translational science. We have a lot of rich information about the structure and function of these pumps. Why not use it?"

News Reference Structures, mechanisms that enable bacteria to resist antibiotics

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