This Week in TB R&D – 15 June 2010

14 Jun 2010
by Working Group

Johns Hopkins Medicine
Johns Hopkins Medicine

On Friday, June 11th, the Johns Hopkins University Center for Tuberculosis Research hosted their annual scientific meeting and the WGND was there to cover the event. Approximately 100-200 people were present including persons from NIH and small pharmaceutical companies. This annual meeting is an opportunity for the epidemiological, clinical and basic researchers to relate their most recent studies and results. Overall, the meeting was dynamic and informative.

The scientific method starts early
The scientific method starts early

The meeting was organized into 3 general sections: Basic Science, Epidemiology and Clinical, and Drugs and Animal Models. There were 23 speakers including the Keynote address by Andrew Nunn from the British Medical Research Council. Andrew spoke about his training experiences in the background of the history of TB clinical trial development over the last 40 years.

The following is a list of all of the speakers with their talk titles. Brief additional comments and/or links are included for most of the talks.

Basic Science:

  1. Gyanu Lamichhane: ‘Remodeling of the peptidoglycan layer during persistent phase of mycobacterial infection’- Gyanu described data and results from previous work which led to the identification and confirmation of nonclassical transpeptide linkages. Interestingly, these nonclassical linkages were first noted in a 1974 publication; however the identity of the transpeptidase which generated them remained unknown. This year, Gyanu and colleagues reported that MT2594, a newly identified L,D-transpeptidase, is responsible for generating nonclassical transpeptide linkages which appear to aid in mycobacterial survival and persistence.
  2. Petros Karakousis: ‘Mycobacterium tuberculosis persistence: Lessons from the guinea pig’- Petros shared data showing how guinea pigs share closer TB caseation morphology to humans than mice. Testing of TB infected guinea pigs with INH led to better insight into why INH killing activity may be altered with prolonged treatment. Moreover, recent results from Petros and colleagues suggest that guinea pigs may be a good model for identifying sterilizing anti-TB drugs.
  3. Lee Klinkenberg: ‘MT1944 is a 2-nitropropane dioxygenase required for Mycobacterium tuberculosis growth and survival in guinea pig lungs’- Using hypoxic models, Lee presented data on the identification and function of MT1944 as a 2-nitropropane dioxygenase.
  4. Seema Thayil: ‘Rv0496 is an exopolyphosphatase required for Mycobacterium tuberculosis growth and survival in guinea pig lungs’-Seema and colleagues identified Rv0496 as an exopolyphosphatase by homology studies.
  5. Ying Zhang: “Update from Zhang Lab’- Three ongoing projects in Ying’s lab were highlighted along with a few publications: Mechanism of rifampicin-dependent MDR-TB, PhoU gene related studies, and L-form bacteria and persisters.
  6. Sanjay Jain: ‘In vivo molecular imaging to understand TB pathogenesis’- Due to the limitations of current investigative tools for TB, Sanjay described the need and potential solution of developing real-time/non-invasive technology using fluorodeoxyglucose (FDG)-positron emission tomography (PET).
  7. Nick Be: ‘Interaction of M. tuberculosis pknD with the host ECM as a mechanism for CNS Invasion’- good, informative discussion of pknD and the extracellular matrix.
  8. David Miranda: ‘Synthetic lethality in M. tb.: harnessing beta-lactams to treat TB’- Results suggest the potential opportunities of finding new TB treatments by investigation of non-essential genes.
  9. Nicole Ammerman: ‘Isoniazid-Resistant M. tb. in the setting of full virulence’- Sigma factors, particularly Sig1 regulates KatG, a critical gene involved in INH resistance.
  10. William Bishai: ‘Overview of the KwaZulu Natal Res. Institute for TB and HIV’

Epidemiology and Clinical:

  1. Adrienne Shapiro: ‘Household contact evaluations of newly diagnosed TB patients in Klerksdorp, South Africa’- Based on observations and data analysis, smear alone is not enough to diagnose TB.
  2. Shama Desai: ‘TB in the foreign-born in New York City’- Shama is Director of the Bureau of TB Control at the NYC Department of Health. According to Shama’s investigation, TB among the foreign born are higher and rising compared to US born individuals. Data suggests that foreign born persons with active TB may have become infected in their home countries, many of which are high burden countries.
  3. Jonathan Golub: ‘Tuberculin skin testing and isoniazid preventive therapy in HIV-infected patients in Rio de Janeiro: Time for a change? Jonathan shared data from the THRio study which is trying to determine whether the time delay from TST and initiation of TB treatment warrants eliminated the TST and treating most if not all persons with INH preventative therapy (IPT).
  4. Celine Gounder: ‘Intensified TB case finding in pregnant women with and without HIV infection in Soweto, South Africa’- TB appears to be the leading killer of women worldwide, especially in sub-Saharan Africa. Celine suggested that based on results collected, ARV and IPT would be beneficial in high-burden settings such as Soweto, South Africa because ~49% of women in these settings have CD4 count of 350.
  5. Maunank Shah: ‘Interferon-gamma release assays for detection of M. tuberculosis infection in children exposed to TB in Soweto, South Africa’- IGRAs potentially more sensitive for detecting TB in the pediatric population.
  6. Amita Gupta: ‘Is TB a risk factor for mother-to-child transmission of HIV?’ Amita discussed the possible correlations.
  7. Helen McIlleron: ‘Pharmacokinetic studies in HIV-infected children with TB’- Helen presented compelling alternative treatment results for ART and TB drugs in children. Key data shared were from the following recent journal publications: Clinical Infectious Diseases, BMC Medicine, and two articles in JAIDS (J Acquired Immune Deficiency Syndromes) [please note: links for JAIDS are for two different abstracts].

Drugs and Animal Models:

  1. Eric Nuermberger: Pharmacodynamics of PA-824 in murine TB models- Eric discussed the stratification of drugs based on concentration dependent killers and time-dependent killers. He then highlighted recent work in collaboration with the TB Alliance on predicting human PA-824 bactericidal activity from PA-824 treatment in murine TB models.
  2. Deepak Almeida: Does PZA have immunomodulatory effects in the treatment of TB in mice?- Deepak presented data from PZA added to rifampicin (R), isoniazid (H), or RH treated M. bovis, which lacks pyrazinamidases, that suggested PZA addition has no immunomodulatory effects on R, H, or RH treatment.
  3. Jacques Grosset: is it possible to “sterilize” TB?- Testing of nude mice with rifapentine suggested that this may be possible.
  4. Claire Andrejak: Towards treatment improvement of NTM infections- Claire discussed non-tuberculosis mycobacteria (NTM)
  5. Paul Converse: BCG vaccination and Buruli ulcer in the mouse- M. ulcerans is increased in Africa. BCG vaccination is also commonly used in Africa. To examine possible links, different mouse strains were vaccinated and infected with M. ulcerans. Different mouse strains react differently. Vaccination apparently decreases M. ulcerans infection possibly through sustained cytokine activation as a result of vaccination.

As you can observe, this was an informative and engaging day of cutting-edge science. Please share your comments below.

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