Sequencing test enables precise identification of drug-resistant TB

October 10, 2017
This photomicrograph reveals Mycobacterium tuberculosis bacteria using acid-fast Ziehl-Neelsen stain; Magnified 1000 X. The acid-fast stains depend on the ability of mycobacteria to retain dye when treated with mineral acid or an acid-alcohol solution such as the Ziehl-Neelsen, or the Kinyoun stains that are carbolfuchsin methods specific for M. tuberculosis. Credit: public domain

Two studies led by the Translational Genomics Research Institute (TGen) and the University of California San Francisco (UCSF) document how a new advanced genetic sequencing approach can help thwart the growing worldwide threat posed by drug-resistant mutations of tuberculosis (TB).

While TB has declined in the U.S. and other developed nations, the infectious lung bacteria remains a major throughout developing nations, estimated to infect a third of the world's population. The threat of TB is increasing in some places as mutant versions of the disease become more and more resistant to current drug treatments.

"We believe that new targeted sequencing technologies can help physicians provide personalized care for patients with drug-resistant TB," said Dr. David Engelthaler, Co-Director of TGen's Pathogen Genomics Division, and senior author of both studies. "Drug-resistance occurs when the wrong antibiotics are prescribed at the wrong time. This new approach is designed to not only help doctors better treat patients, but to help slow or stop the global threat of multi-drug resistant TB."

One of the TGen-UCSF studies—Cryptic Micro-heteroresistance Explains M. tuberculosis Phenotypic Resistance—published June 14 in the American Journal of Respiratory and Critical Care Medicine, concludes that using "a targeted next generation sequencing (NGS) approach ... dramatically reduces sequencing error." Such error, inherent in DNA sequencing systems, would otherwise prevent the ability to detect very small, hidden populations of drug-resistant bacteria growing in the lung.

In both studies, the TGen-UCSF team used Single Molecule-Overlapping Reads (SMOR) technology—invented at TGen—which precisely identifies variants of TB, even in cases where an older technology, known as Sanger sequencing, found no drug-resistant mutations.

A version of this SMOR test is being developed that could be easily deployed to under-developed areas where it may be most needed.

"A user-friendly kit-based version of our assay is currently under development for use with the new desktop DNA Sequencers for rapid drug susceptibility testing in limited resource settings," said Dr. Engelthaler. "It seems counterintuitive to develop cutting edge genomic solutions for problems in our under-developed world, but we are adapting that technology in ways that can be accessible by anyone, nearly anywhere."

Identifying rapidly mutating, drug-resistant strains of TB is the greatest challenge to eradicating this disease, which in 2015 infected 10.4 million and killed 1.8 million people across the globe, according to the U.S. Centers for Disease Control and the World Health Organization—nearly 5,000 deaths per day worldwide.

"Despite our now global society, it is difficult for many of us to imagine places where an infection, fully curable with antibiotics developed decades ago, can kill more people in their prime than cancer. Unfortunately, due to health systems abroad weakened by neglect and chronic underfunding, highly resistant TB is becoming the 'new normal' TB. Given that we are and have always been a 'melting pot' country and beacon of hope for so many, we will certainly see these cases in the United States," said Dr. John Metcalfe, a pulmonary care specialist and Associate Professor at the UCSF School of Medicine, and the lead author of both TGen-UCSF studies.

The second TGen-UCSF study—Mycobacterium tuberculosis subculture results in loss of potentially clinically relevant heteroresistance—published Sept. 11 in the journal Antimicrobial Agents and Chemotherapy, also used "ultra-deep next-generation" SMOR sequencing to examine potentially drug resistant variants of TB.

"This report further documents the previously under-described nature of the drive of the M. tuberculosis organism to mutate and become resistant to our antibiotics," said Dr. Metcalfe, "and further emphasizes the need for additional study of the effects of this phenomenon on both clinical diagnostics and patient outcomes."

Explore further: Bacteria from cystic fibrosis patient could help fight antibiotic-resistant TB

Related Stories

Bacteria from cystic fibrosis patient could help fight antibiotic-resistant TB

June 23, 2017
A newly discovered antibiotic, produced by bacteria from a cystic fibrosis patient, could be used to treat cases of drug-resistant tuberculosis (TB). This is the finding of a team of scientists from Cardiff University's School ...

MRSA detection technology developed by TGen-NAU is granted first patent

June 15, 2016
Antibiotic-resistant infections should be easier to detect, and hospitals could become safer, thanks to a technology developed by the Translational Genomics Research Institute (TGen) and Northern Arizona University (NAU), ...

TGen and NAU patent for new pandemic flu test is approved

October 8, 2014
The federal government has awarded a patent to the Translational Genomics Research Institute (TGen) and Northern Arizona University (NAU) for a test that can detect—and assist in the treatment of—the H1N1 pandemic flu ...

Revealing the global burden of drug-resistant tuberculosis in children

June 27, 2016
A new study examining the burden of drug-resistant tuberculosis (TB) across the globe has highlighted the importance of the disease among children.

Bacteria from cystic fibrosis patient could help thwart antibiotic-resistant TB

June 14, 2017
The number of drug-resistant tuberculosis (TB) cases is rising globally. But a newly discovered natural antibiotic—produced by bacteria from the lung infection in a cystic fibrosis patient—could help fight these infections. ...

Turning to freshwater sources to fight drug-resistant tuberculosis, other infections

April 8, 2015
The discovery of antibiotics produced by soil fungi and bacteria gave the world life-saving medicine. But new antimicrobials from this resource have become scarce as the threat of drug resistance grows. Now, scientists have ...

Recommended for you

New insights into herpes virus could inform vaccine development

October 18, 2017
A team of scientists has discovered new insights into the mechanisms of Epstein-Barr virus (EBV) infection, as well as two antibodies that block the virus' entry into cells. The findings, published in Proceedings of the National ...

Pair of discoveries illuminate new paths to flu and anthrax treatments

October 17, 2017
Two recent studies led by biologists at the University of California San Diego have set the research groundwork for new avenues to treat influenza and anthrax poisoning.

Portable 3-D scanner assesses patients with elephantiasis

October 17, 2017
An estimated 120 million people worldwide are infected with lymphatic filariasis, a parasitic, mosquito-borne disease that can cause major swelling and deformity of the legs, a condition known as elephantiasis. Health-care ...

New tools to combat kidney fibrosis

October 16, 2017
Interstitial fibrosis – excessive tissue scarring – contributes to chronic kidney disease, which is increasing in prevalence in the United States.

How hepatitis C hides in the body

October 13, 2017
The Hepatitis C (HCV) virus is a sly enemy to have in one's body. Not only does it manage to make itself invisible to the immune system by breaking down communication between the immune cells, it also builds secret virus ...

Largest study yet of malaria in Africa shows historical rates of infection

October 12, 2017
(Medical Xpress)—A team of researchers with members from the Kenya Medical Research Institute, the University of Oxford and the University of KwaZulu-Natal has conducted the largest-ever study of the history of malaria ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.