Senior Scholar Award in Global Infectious Disease
Abigail A. Salyers, Ph.D.
University of Illinois - Urbana-Champaign

Resistance Gene Flow in the Human Colonic Microflora

Antibiotics play a critical role in modern medicine. Not only do they cure debilitating and potentially fatal bacterial diseases such as pneumonia, they also make surgery and cancer chemotherapy much less risky than they would be if antibiotics were not available to prevent or cure the overwhelming bacterial infections that can be a side effect of these procedures. Yet, bacteria are becoming steadily more resistant to antibiotics, making antibiotics less effective. Scientists suspect that a major contributor to increasing bacterial resistance to antibiotics is the ability of bacteria to acquire genes from each other, genes that contain the blueprint for making the recipient bacterium resistant to an antibiotic. One site in which such an exchange of genes could occur is the human colon, where a dense and diverse population of bacteria resides throughout life. Some of the bacteria that reside in the colon can cause serious post-surgical infections. Even if they do not cause infection, they have the potential to transfer resistance gene to bacteria that can cause human infections, as these bacteria pass through the colon.

Although some work has been done to determine whether exchanges of resistance genes occur among numerically minor populations of colonic bacteria, only recently have scientists begun to monitor the numerically predominant populations of colonic bacteria, the populations that are most likely to be responsible for resistance gene transfer. Previously, we established that one numerically predominant genus of colonic bacteria, Bacteroides, is very actively circulating antibiotic resistance genes. Bacteroides species account for about one-fourth of the bacteria in the colon. The funded proposal addresses the role of other numerically predominant genera of colonic bacteria, a mixture of gram-positive obligate anaerobes about which little is known. We plan to characterize gene transfer elements called conjugative transposons that appear to be capable of moving between these gram-positive bacteria and the gram-negative bacteria such as Bacteroides species. We also plan to determine whether other vehicles for resistance gene transfer exist in these numerically predominant groups of bacteria. The planned work will also indicate whether there are limitations to the distance resistance genes can travel among different genera and might point to types of conditions that stimulate or facilitate gene transfer. The goal of this work is to obtain for the first time the type of information about the types of gene transfer that occur in the colon, information that may guide the future design of antibiotics and ways of administering antibiotics, with a view to decreasing the rate of increase in the incidence of antibiotic resistant bacteria. Results of this work will also have implications for the debate over the use of antibiotics as food additives in agriculture, since one possible outcome of the movement of resistant bacteria from food animals to the human colon is that incoming animal bacteria can transfer their resistance genes to bacteria that normally occupy the colon.

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