A new study published in Nature has illustrated the structure of the T4SS complex, providing a blueprint that could help researchers in designing drugs that could slow the progression of antibiotic resistance. With antibiotic-resistant bacteria on the rise, scientists have been searching for ways to shut down the Type IV secretion system (T4SS), a protein complex on the outer envelope of bacterial cells that helps them exchange DNA with neighboring bacteria and resist antibiotics.

The research was conducted in collaboration between UT Southwestern computational biologist Dr. Qian Cong, Ph.D., and molecular biologists at the University of London, Dr. Gabriel Waksman, Ph.D. Dr. Waksman and his colleagues have worked for more than two decades to understand the T4SS complex, especially how it forms a thin, hollow structure called a pilus, which connects to nearby bacteria to share genes. In this project, the team used cryo-electron microscopy (cryo-EM) to elucidate the structure of T4SS.

In the meantime, Dr. Cong used her background in statistics and machine learning to analyze T4SS protein sequences from several bacteria to generate structural predictions, which were compared to cryo-EM data. Her computational analysis supported the cryo-EM data collected by Dr. Waksman. With the prediction based on computational data in hand, Dr. Waksman’s team was able to make specific mutations within the relevant pieces of the complex and validate Dr. Cong’s hypothesis in live bacteria. 

(Source: https://theprint.in/health/scientists-determine-structure-of-key-player-in-antibiotic-resistance/1087525/ )