Scientists at La Trobe University and the University of Queensland describe in Nature Communications how proteins in the outer membrane of bacteria are able to stick to and populate parts of the human body. This new information paves the way for the development of innovative treatments for preventing and curing infections, in what could be a significant step forward for new antimicrobial development, according to the researchers.

Their study (“Unique structural features of a bacterial autotransporter adhesin suggest mechanisms for interaction with host macromolecules”) focused on UpaB, the “superglue” protein of uropathogenic E. coli known to cause urinary tract infections within 50% of women within their lifetime. Similar proteins are found in the outer membrane of other pathogens responsible for infections ranging from life-threatening food poisoning to whooping cough, meningitis, typhus fever, and chlamydia. 

“Autotransporters are the largest family of outer membrane and secreted proteins in Gram-negative bacteria. Most autotransporters are localized to the bacterial surface where they promote colonization of host epithelial surfaces. Here we present the crystal structure of UpaB, an autotransporter that is known to contribute to uropathogenic E. coli (UPEC) colonization of the urinary tract. We provide evidence that UpaB can interact with glycosaminoglycans and host fibronectin,” the investigators wrote.

“Unique modifications to its core β-helical structure create a groove on one side of the protein for interaction with glycosaminoglycans, while the opposite face can bind fibronectin. Our findings reveal far greater diversity in the autotransporter β-helix than previously thought, and suggest that this domain can interact with host macromolecules. The relevance of these interactions during infection remains unclear.”

Lead researcher at La Trobe University, Begoña Heras, PhD, said the study provides unprecedented fundamental science that could inform future solutions to the world health crisis in antibiotic resistance.

“The knowledge we now have on this bacteria’s protein gives us the ability to block the bacteria sticking to different parts of the human body,” she explained. “Antibiotic resistance is an urgent, global problem and this information gives us an important opportunity to develop new antimicrobial treatments. Naturally, this is the next step for this research.”

La Trobe researcher Jason Paxman, PhD, added that there is a flip-side to these bacterial proteins in that they could be harnessed for good. 

“There is nothing like these bacterial proteins in modern medicine; bacteria have had thousands of years to develop these adhesive proteins,” said Paxman. “These findings could open up new opportunities such as delivering targeted therapies to parts of the human body, which could even help in the fight against cancer down the line.”

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