Featured Research

from universities, journals, and other organizations

Multiple mutations often needed to make TB bacteria drug resistant

Date:
September 1, 2013
Source:
Rutgers Biomedical and Health Sciences
Summary:
The gene mutation process that creates drug resistance in a tuberculosis-causing bacterium often requires more than one step. It is not just a single mutation, but a series, according to new research.

Tuberculosis (TB) drug resistance is not an all-or-none phenomenon, according to new research from Rutgers, The State University of New Jersey. Rather, TB-causing bacteria often accumulate mutations in a step-wise fashion, with the initial mutation having minimal impact but poising the bug to later develop high-level resistance upon acquisition of other mutations. The study appears in Nature Genetics .

Related Articles


The anti-TB drug ethambutol blocks bacterial genes required for synthesis of the bug's protective cell wall. Several mutations in these bacterial genes (collectively called the embCAB operon) have been identified in drug-resistant strains of TB, and single mutations are widely thought to confer resistance in one fell swoop. But not all bugs carrying embCAB mutations become ethambutol-resistant and not all resistance strains contain these mutations, suggesting that the story is much more complicated.

David Alland, director of the Center for Emerging and Re-Emerging Pathogens at Rutgers New Jersey Medical School, and colleagues had previously shown expressing single embCAB mutations in drug sensitive bugs rendered them only slightly more drug resistant than normal and failed to explain full-blown resistance. The group now identifies new mutations that contribute to drug resistance, with the level of resistance depending on the unique combination of mutations in a given bacterial isolate.

One of the newly identified mutations -- in a bacterial gene called Rv3806c -- ramps up production of a substrate used by the embCAB-encoded enzymes to generate the bug's cell wall. This excess substrate then binds to the enzymes, potentially limiting the amount of drug that can bind. However, the Rv3806c mutation alone only modestly increased drug resistance. But when combined with other mutations, it generated high-level ethambutol resistance. Surprisingly, they also discovered "synonymous" DNA mutations (ones that don't change the amino acid sequence of the resulting protein) in a related protein called Rv3792 that also contributed to drug resistance.

Alland's group suggests that bugs with single mutations, for example those in Rv3806c and Rv3792, represent a pre-resistant state, in which the bug is poised for full-blown drug resistance upon the acquisition of a 'second hit' mutation. Identification of patients infected with 'pre-resistant' bugs may allow doctors to increase drug dosages or alter treatment strategies before full-scale drug resistance develops.

This work was supported in part by National Institute of Allergy and Infectious Diseases, US National Institutes of Health grants AI080653, AI065663 and AI037139 and by Pathogen Functional Genomics Resource Center contract N01-AI5447.


Story Source:

The above story is based on materials provided by Rutgers Biomedical and Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hassan Safi, Subramanya Lingaraju, Anita Amin, Soyeon Kim, Marcus Jones, Michael Holmes, Michael McNeil, Scott N Peterson, Delphi Chatterjee, Robert Fleischmann & David Alland. Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-D-arabinose biosynthetic and utilization pathway genes. Nature Genetics, 01 September 2013 DOI: 10.1038/ng.2743

Cite This Page:

Rutgers Biomedical and Health Sciences. "Multiple mutations often needed to make TB bacteria drug resistant." ScienceDaily. ScienceDaily, 1 September 2013. <www.sciencedaily.com/releases/2013/09/130901153345.htm>.
Rutgers Biomedical and Health Sciences. (2013, September 1). Multiple mutations often needed to make TB bacteria drug resistant. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2013/09/130901153345.htm
Rutgers Biomedical and Health Sciences. "Multiple mutations often needed to make TB bacteria drug resistant." ScienceDaily. www.sciencedaily.com/releases/2013/09/130901153345.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins