We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us

Download Mobile App




New Version of Old Drug Shows Promise for Treating Drug-Resistant Tuberculosis

By LabMedica International staff writers
Posted on 15 Jun 2015
A team of molecular microbiologists has determined the mechanism by which the Streptomyces-derived antibiotic griselimycin blocks the growth of Mycobacterium tuberculosis, the bacterium responsible for causing more than eight million cases of tuberculosis annually on a worldwide basis.

Investigators from the Helmholtz Center for Infection Research (Braunschweig, Germany), other German research institutes, and the biomedical company Sanofi (Paris, France) were interested in exploring the possibility of using griselimycin or one of its derivatives for treating drug resistant tuberculosis; while this drug had been evaluated in the 1960's it had suffered in comparison to others. More...
However, M. tuberculosis has developed resistance to most of those other drugs, and development of replacements is a top priority.

The investigators reported in the June 5, 2015, issue of the journal Science that a variant of griselimycinm, cyclohexylgriselimycin, was particularly effective against M. tuberculosis, in cells and when administered orally to an animal model.

The effectiveness of cyclohexylgriselimycin was found to be due to the drug's inhibition of the M. tuberculosis DNA polymerase sliding clamp DnaN. A DNA clamp, also known as a sliding clamp, is a protein fold that serves as a processivity-promoting factor in DNA replication. Processivity is an enzyme's ability to catalyze consecutive reactions without releasing its substrate. As a critical component of the DNA polymerase III holoenzyme, the clamp protein binds DNA polymerase and prevents this enzyme from dissociating from the template DNA strand. The clamp-polymerase protein–protein interactions are stronger and more specific than the direct interactions between the polymerase and the template DNA strand; because one of the rate-limiting steps in the DNA synthesis reaction is the association of the polymerase with the DNA template, the presence of the sliding clamp dramatically increases the number of nucleotides that the polymerase can add to the growing strand per association event. The presence of the DNA clamp can increase the rate of DNA synthesis up to 1,000-fold compared with a nonprocessive polymerase.

As inhibiting the DNA clamp is a completely different mechanisms from those of antibiotics now used against tuberculosis and other bacterial pathogens, the investigators consider that the risk of developing resistance to cyclohexylgriselimycin is low.

"We hope that cyclohexylgriselimycin will become an agent that can even be used against resistant tuberculosis pathogens in the future and contributes to a more successful fight against this dreadful disease," said senior author Dr. Rolf Müller, head of the department of microbial natural products at the Helmholtz Centre for Infection Research. "In the tuberculosis pathogen, the substance binds to the so-called DNA clamp and thus suppresses the activity of the DNA polymerase enzyme, which multiplies the genetic information inside the cell. We resumed the work on this agent and optimized it such that it shows excellent activity in the infection model—even against multi-resistant tuberculosis pathogens."

Related Links:

Helmholtz Centre for Infection Research
Sanofi



Gold Member
Antipsychotic TDM Assays
Saladax Antipsychotic Assays
Portable Electronic Pipette
Mini 96
New
Blood Glucose Test Strip
AutoSense Test
New
Pipette
Accumax Smart Series
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Molecular Diagnostics

view channel
Image: Over 100 new epigenetic biomarkers may help predict cardiovascular disease risk (Photo courtesy of 123RF)

Routine Blood Draws Could Detect Epigenetic Biomarkers for Predicting Cardiovascular Disease Risk

Cardiovascular disease is a leading cause of death worldwide, yet predicting individual risk remains a persistent challenge. Traditional risk factors, while useful, do not fully capture biological changes... Read more

Hematology

view channel
Image: New research points to protecting blood during radiation therapy (Photo courtesy of 123RF)

Pioneering Model Measures Radiation Exposure in Blood for Precise Cancer Treatments

Scientists have long focused on protecting organs near tumors during radiotherapy, but blood — a vital, circulating tissue — has largely been excluded from dose calculations. Each blood cell passing through... Read more

Immunology

view channel
Image: The VENTANA HER2 (4B5) test is now CE-IVDR approved (Photo courtesy of Roche)

Companion Diagnostic Test Identifies HER2-Ultralow Breast Cancer and Biliary Tract Cancer Patients

Breast cancer is the most common cancer in Europe, with more than 564,000 new cases and 145,000 deaths annually. Metastatic breast cancer is rising in younger populations and remains the leading cause... Read more

Pathology

view channel
Image: An adult fibrosarcoma case report has shown the importance of early diagnosis and targeted therapy (Photo courtesy of Sultana and Sailaja/Oncoscience)

Accurate Pathological Analysis Improves Treatment Outcomes for Adult Fibrosarcoma

Adult fibrosarcoma is a rare and highly aggressive malignancy that develops in connective tissue and often affects the limbs, trunk, or head and neck region. Diagnosis is complex because tumors can mimic... Read more

Technology

view channel
Image: Conceptual design of the CORAL capsule for microbial sampling in the small intestine (H. Mohammed et al., Device (2025). DOI: 10.1016/j.device.2025.100904)

Coral-Inspired Capsule Samples Hidden Bacteria from Small Intestine

The gut microbiome has been linked to conditions ranging from immune disorders to mental health, yet conventional stool tests often fail to capture bacterial populations in the small intestine.... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.