Navigation Links
Researchers identify a new mechanism of TB drug resistance
Date:6/12/2013

Pyrazinamide (PZA)a frontline tuberculosis (TB) drugkills dormant persister bacteria and plays a critical role in shortening TB therapy. PZA is used for treating both drug susceptible and multi-drug resistant TB (MDR-TB) but resistance to PZA occurs frequently and can compromise treatment.

A recent study, led by researchers at the Johns Hopkins Bloomberg School of Public Health and Huashan Hospital, Fudan University, has identified a new mechanism for PZA-resistance, which provides new insight into the how this mysterious drug works. The study is available online June 12 in the journal Emerging Microbes and Infections.

Previously, the Johns Hopkins group identified mutations in the pncA gene and the rpsA gene as the primary causes for PZA resistance. According to the study authors, resistance to PZA is most commonly caused by mutations in the pncA gene encoding enzyme nicotinamidase/pyrazinamidase, which converts the prodrug PZA to the active form pyrazinoic acid (POA), and sometimes associated with mutations in the drug target RpsA (ribosomal protein S1). The active form of PZA, POA, interacts chemically with RpsA to block the trans-translation process, which is essential for bacterium's survival under stress conditions.

However, for unknown reasons, some PZA-resistant TB bacteria lack mutations in pncA or rpsA. The current study suggests that mutations in the panD gene may also be involved. PanD encodes aspartate decarboxylase, which is involved in synthesis of the amino acid β-alanine, a precursor for pantothenate (which is vitamin B5) and co-enzyme A biosynthesis. The panD mutations were identified not only in mutants isolated from in vitro but also in clinical isolates such as in the naturally PZA-resistant bacterium M. canettii strain and in a PZA-resistant MDR-TB strain.

"There is significant recent interest in understanding PZA, since it is the only TB drug that cannot be replaced without compromising the efficacy of the therapy. It's indispensible," said Ying Zhang, MD, PhD, senior author of the study and professor in the Bloomberg School's W. Harry Feinstone Department of Molecular Microbiology and Immunology. "The process of identifying the correct resistance mutations was quite tedious and took about two years to complete. However, the work led to the identification of a potential new mechanism of PZA resistance."

While more study is needed, Zhang and his colleagues believe panD could be a potential target for new antibiotic therapies.

The study was conducted in collaboration with researchers Wenhong Zhang and Jiazhen Chen from Fudan University. The authors of "Mutations in panD encoding aspartate decarboxylase are associated with pyrazinamide resistance in Mycobacterium tuberculosis" are Shuo Zhang, Jiazhen Chen, Wanliang Shi, Wei Liu, Wenhong Zhang, and Ying Zhang.


'/>"/>

Contact: Tim Parsons
tmparson@jhsph.edu
410-955-7619
Johns Hopkins University Bloomberg School of Public Health
Source:Eurekalert

Related medicine news :

1. Mount Sinai researchers provide 1st prospective characterization of a genetic subtype of autism
2. Obesity can be predicted from infancy, CWRU researchers find
3. Quality-of-life issues need to be addressed for CML patients, Moffitt researchers say
4. With new $1.7 million grant, U-M, Johns Hopkins researchers will develop dementia treatment tool
5. Voices Against Brain Cancer Comments on New Discovery Made by Researchers in Regards to the Tie between Brain Cancer and Genetics
6. ASTRO awards 3 distinguished physicians and researchers with Societys highest honor
7. Researchers identify genetic signature of deadly brain cancer
8. Dartmouth researchers test safety of Nivolumab in kidney cancer
9. Researchers narrow the search for biomarkers of drug resistance in head and neck cancer patients
10. Researchers investigate a less toxic radiation treatment for HPV-Positive oropharynx cancer
11. Researchers discover new weapon in fight against cervical cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet supplements owned by ... to enhance the health of felines. The formula is all-natural and is made from ... the PawPaws Cat Kidney Support Supplement Soft Chews are Astragalus Root Extract ...
(Date:6/25/2016)... ... 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 due to ... a new, often overlooked aspect of head lice: the parasite’s ability to live away from ... common occurrence, but a necessary one in the event that lice have simply gotten out ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, Van Mitchell, Secretary ... Work award to iHire in recognition of their exemplary accomplishments in worksite health promotion. ... Maryland Workplace Health & Wellness Symposium at the BWI Marriott in Linthicum Heights. iHire ...
(Date:6/24/2016)... ... June 24, 2016 , ... Marcy was in a crisis. Her son James, eight, ... at his family verbally and physically. , “When something upset him, he couldn’t control his ... it. He would throw rocks at my other children and say he was going to ...
(Date:6/24/2016)... ... ... Topical BioMedics, Inc, makers of Topricin and MyPainAway Pain Relief Products, join The ‘Business for ... $12 an hour by 2020 and then adjusting it yearly to increase at the same ... wage, assure the wage floor does not erode again, and make future increases more predictable. ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016 ... announced the addition of the " Global Markets ... This report focuses ... an updated review, including its applications in various applications. ... market, which includes three main industries: pharmaceutical and biotechnology, ...
(Date:6/24/2016)... , June 24, 2016 Research ... World Market for Companion Diagnostic Tests" report to their ... Market for Companion Diagnostics The World Market ... and personalized medicine diagnostics. Market analysis in the report includes ... Test Market (In Vitro Diagnostic Kits) by Region (N. America, ...
(Date:6/23/2016)... , June 23, 2016  MedSource announced today ... its e-clinical software solution of choice.  This latest ... possible value to their clients by offering a ... preferred relationship establishes nowEDC as the EDC platform ... MedSource,s full-service clients.  "nowEDC has long been a ...
Breaking Medicine Technology: