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TB Notes Newsletter

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No. 1, 2012


Molecular Detection of Drug Resistance Clinical Service

Rapid and accurate identification of drug-resistant TB is essential for control and prevention of TB. Science and technology have merged to produce new diagnostic testing options for the detection of drug-resistant TB; however, these molecular assays are not currently widely available. Therefore, DTBE’s Laboratory Branch consolidated available knowledge, conducted translational research and development to assemble a molecular testing platform, and implemented a clinical service that provides rapid information about drug resistance to clinicians.

Research and development included a comprehensive survey of nine genetic loci known to harbor mutations associated with resistance to both first-line and second-line anti-tuberculosis drugs in over 300 isolates of Mycobacterium tuberculosis. The resultant genotypic data set was compared with culture-based drug-susceptibility data to determine accuracy for each locus. These values served as the analytic basis for the molecular detection of drug resistance (MDDR) clinical service.  Since September 2009, the Laboratory Branch has offered the MDDR service nationally to patients and their providers.  The service detects mutations associated with resistance to eight first-line and second-line TB drugs; average turnaround time is 2 days, compared to the turnaround time of 28–35 days for culture-based methods. It provides rapid detection of drug resistance or confirmation of known drug resistance and provides information that may be used by clinicians to guide therapy decisions. The service has been well received by the public health community and has been used by 47 states and territories. Currently, the Laboratory Branch is validating a new method for detecting mutations associated with rifampin and isoniazid resistance in patient specimens known to contain M. tuberculosis as determined by amplification-based assays. This addition to the MDDR service is scheduled to begin in early 2012.

In addition to affecting patient management decisions, the results provided by the MDDR clinical service also affect those related to infection control and public health interventions.  Rapid confirmation of drug-resistant TB and guidance on selection of an effective drug regimen will reduce delay in the adequate treatment of TB and could translate into decreased transmission of TB.

Complete information about the service can be found on the CDC website.

—Reported by Bonnie Plikaytis
Div of TB Elimination

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Review of Southeastern Mycobacteria Meeting

The fourth bi-annual Southeastern Mycobacteria Meeting took place January 14, 2012, at Emory University’s Claudia Nance Rollins Building.  Attendees came from academia, government, and industry, representing Emory University, University of Georgia, University of North Carolina at Chapel Hill, Duke University, Research Triangle Institute, University of Louisiana-Lafayette, Health Sciences Center of Louisiana State University, Southern University at New Orleans, University of Alabama at Birmingham (UAB), Tulane National Primate Research Center, Tulane University, University of Florida, and CDC.  Post-doctoral fellows and graduate students were especially encouraged to present their work in posters and oral presentations.

The day’s agenda included a series of short talks presenting ongoing research projects and two poster sessions.  In one talk, Ruth Napier, a graduate student at Emory University, presented her work demonstrating utility of an ABL-family tyrosine kinase inhibitor (imatinib) in reducing M. tuberculosis entry and survival within macrophages.  Frank Wolschendorf from UAB described research using M. tuberculosis sensitivity to copper as a possible new therapeutic.  His most recent experiments included a high throughput screen to identify compounds that could affect copper poisoning of M. tuberculosis.  Graduate student Meghan Feltcher from UNC described her recent attempts to decipher the M. tuberculosis SecA2 protein translocation system.  She demonstrated that unlike proteins exported through the traditional Sec system, those exported via SecA2 do not contain a signal sequence and are targeted to the SecA2 pathway by the mature protein sequence.  She also showed that although the two SecA2 substrates thus far identified are lipoproteins, lipid modification is not a requisite for SecA2 export.

The keynote address, given by Eric Rubin, MD, PhD, of Harvard University, was titled, “Protein synthesis and degradation in mycobacteria: lost in mistranslation.”  Dr. Rubin described a new, cutting-edge technique that will enable the role(s) of individual mycobacterial proteins to be explored via targeted proteolysis. He also presented data on protein mistranslation in mycobacteria and its possible consequences, including implications for drug resistance.

Laboratory Branch Chief Michael Iademarco, MD, MPH, gave a presentation describing the role of CDC’s National Laboratory in TB elimination. Members of the Laboratory Branch Applied Research Team (Seidu Malik, Subhi Nandakumar, Suraj Sable, and Melisa Willby) presented posters detailing current research projects.

This excellent regional meeting brought together a diverse group of individuals conducting research on a wide variety of topics in mycobacteria to foster information exchange and collaborative opportunities.

—Submitted by Melisa Willby, PhD
Applied Research Team, Laboratory Branch, DTBE

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