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David thanassi

A research team led by David Thanassi, Zhang family professor and chair of the Department of Microbiology and Immunology at the Renaissance School of Medicine, has used molecular biology and cryoelectron microscopy to successfully unravel the structure of bacterial appendages called P pili. These pili are deployed by uropathogenic strains of Escherichia coli bacteria that cause kidney infections. The structure of P pili has been elusive to scientists for many years. The finding, published in Nature Communications, is a key step in order to target P pili in the infection process.

P pilus assembly complex
Structure of a bacterial P pili assembly complex. The P pilus fiber is depicted in green as it is being assembled and secreted across the bacterial outer membrane by the usher-chaperone pili assembly machinery (blue and orange, respectively). Photo by David Thanassi

“Given their central role in initiating and sustaining infection, there is intense interest in understanding the mechanisms of pilus assembly and function,” said Thanassi, who is lead author of the research findings. “Our report of the structure of P pili may help to pave the way for a method to interfere with pilus assembly or function in order to develop novel therapeutics as a potential alternative to antibiotics. A new approach may help us to better treat urinary tract infections and other infectious diseases.”

Bacterial infections of the urinary tract are common and associated with high rates of antibiotic resistance, which is a reason why Thanassi and the research team are focusing on pili structures involved in these infections. Kidney infections themselves pose a major risk for the bacteria to enter the bloodstream, an action that could result in lethal bacterial sepsis.

This latest work builds on previous research from the team and other scientists that revealed the structure of related bacterial appendages, termed type 1 pili, which facilitate colonization of the bladder. To further understand this research, reported in Nature in 2018, and the research approach overall, see this news and video.

The research for the recent paper was supported by grants from the National Institutes of Health.

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