Manipulating Mycobacteria—Bacteria can exchange genetic information amongst each other by transferring plasmids—small, circular DNA that are different from chromosomal DNA. Scientists capitalize on this natural process by constructing artificial plasmids to experimentally manipulate bacteria, helping them to understand the genetic basis of important traits. Since the bacterium that causes TB—Mycobacterium tuberculosis—can be lethal, labs often use the closely related M. smegmatis instead. M. smegmatis normally resists genetic alteration by plasmid DNA. But 25 years ago, Dr. William Jacobs isolated a mutant strain, called mc2155 that does allow plasmid transfer. Although the mc2155 mutant revolutionized mycobacteria genetics, why it can be genetically manipulated was not known until recently. In the September 2014 issue of the Proceedings of the National Academies of Sciences, Dr. Jacobs reports that the EptC gene in wildtype M. smegmatis encodes a protein that binds to plasmid DNA and prevents its transfer during cell division. In mc2155, a loss-of-function mutation in this gene permits plasmid DNA to pass on to new generations of cells, allowing scientists to genetically manipulate the bacteria. Mc2155 has helped scientists understand why certain mycobacteria cause disease or are resistant to antibiotics, and has helped in developing therapies. Dr. Jacobs is professor of microbiology & immunology and of genetics at Einstein and a Howard Hughes Medical Institute investigator.
Posted on: Tuesday, April 21, 2015