A newly published study led by Dr. Jiqiang Ling, assistant professor in the Department of Microbiology & Molecular Genetics, could change the way researchers look at variations in protein synthesis and could help researchers better understand how pathogens can survive immune responses and antimicrobial treatment.
The article, “Heterogeneity of Stop Codon Readthrough in Single Bacterial Cells and Implications for Population Fitness”, is slated to be published in Molecular Cell’s print edition on Sept. 7 and is currently available online. It describes how researchers from UTHealth, Yale University and Rice University developed a reporter system to visualize the differences of errors during protein synthesis among individual bacterial cells. The study, which took about three years to complete, yielded unexpected results – cells that are slow at making proteins also tend to make more errors.
“This blows my mind as the research field has long been thinking that there is a trade-off between speed and accuracy during protein synthesis,” Dr. Ling said.
The study also showed that individual cells with high errors can grow better under poor-nutrient conditions.
“Sometimes making some errors may help your life, which sounds counterintuitive,” Dr. Ling said.
These findings are particularly important as antimicrobial resistance has become an increasingly severe global threat to human health. A significant reason for the failure of antibiotics is due to a small fraction of pathogen cells evading antibiotics and forming persisters, which can reestablish the bacterial population after antibiotic treatment stops. How persisters are formed is not fully understood
“Our study reveals that bacteria use an active mechanism to fluctuate in the levels of protein synthesis errors among individual cells to facilitate adaptation to changing environments,” Dr. Ling said. “This opens the door for future studies to track protein synthesis errors in pathogen cells in their native environment and help understand how pathogens survive host immune responses and antimicrobial treatment.”
Dr. Yongqiang Fan, a postdoctoral fellow in the Department of Microbiology and Molecular Genetics, and Christopher Evans, a post-candidacy PhD student in the Microbiology and Infectious Diseases Program, are co-first authors of this study. Co-authors include Kalyn Weiss, a first-year graduate student in the Microbiology and Infectious Diseases Program, and Dr. Bill Margolin, professor of Microbiology and Molecular Genetics.
The study joins Dr. Ling’s 15 other published articles since starting his lab in 2013, which have appeared in journals such as the New England Journal of Medicine, American Journal of Human Genetics, Nucleic Acids Research and Nature Review in Microbiology.
“This project has seen many obstacles,” Dr. Ling said. “We are very happy that it is eventually accepted by Molecular Cell.”