DNA Polymerase Promotes Tuberculosis Drug Resistance

Researchers have found that possessing multiple copies of the DNA-repair enzyme DNA polymerase (DnaE) gives Mycobacterium tuberculosis (Mtb) a survival advantage by inducing mutations in the population of organisms that resist initial antibiotic treatment and encouraging the rise of drug-resistant mutants.

Tuberculosis kills almost two million people each year, and eight million people develop active TB annually. The medical community is especially concerned by the upsurge in cases of multidrug-resistant tuberculosis.

Investigators at the National Institute of Allergy and Infectious Diseases (NIAID, Bethesda, MD, USA) identified dnaE2 as a gene that was upregulated in vitro by several DNA damaging agents, as well as during infection of mice. Loss of the protein produced by this gene reduced both survival of the bacillus after UV (ultraviolet) irradiation and the virulence of the organism in mice. These findings, published in the April 18, 2003, issue of Cell, explain why UV irradiation of Mtb resulted in increased mutation frequency in the surviving fraction.

"We were surprised to find that MTb uses an enzyme from the major DNA polymerase replication family. In other organisms, including humans, such DNA polymerases are responsible for making perfect copies of DNA before the cell divides. Other DNA polymerases in this family are like straight-A students; they perform almost flawlessly. This is the first error-prone DNA polymerase from this family to be identified,” said contributing author Dr. Clifton Barry, a researcher at NIAID.




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National Institute of Allergy and Infectious Diseases (NIAID)