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It is also likely that compensatory mutations take place after an initial drug-resistance mutation. The sequencing of a set of evolved strains is now under way to identify such compensatory mutations. Edward Nardell of Brigham and Women’s Hospital stated that he and colleagues at the South African Medical Research Council and CDC have been researching the transmission of MDR TB from patients directly to sentinel guinea pigs to replicate and expand upon some of the early research of Richard Riley discussed by Murray.

Second, because about half of these patients had never before been treated for TB, and 85 percent had a genetically similar strain, resistance was likely transmitted rather than acquired. The progression of XDR TB from June 2006 to 2007 is depicted in Figure 3-2, which shows facilities within KwaZulu-Natal Province where at least one XDR TB case was described or diagnosed. There were 6 such  A compensatory mutation occurs when the fitness loss caused by one mutation is corrected by that mutation’s epistatic interaction with a second mutation at a different location within the genome.

The results of these experiments 38 THREAT OF DRUG-RESISTANT TUBERCULOSIS have been confirmed in recent years by multiple laboratories and are consistent with what is now known about MDR TB drug resistance. It is thought that the setting in which strains are transmitted acts as an “evolutionary” barrier: the less fit mutants are weeded out, and those mutants with greater fitness are selected. It is also likely that compensatory mutations take place after an initial drug-resistance mutation. The sequencing of a set of evolved strains is now under way to identify such compensatory mutations.

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