Navigation Links
New findings on drug tolerance in TB suggest ideas for shorter cures

New findings on how tuberculosis (TB) bacteria develop multi-drug tolerance point to ways TB infections might be cured more quickly.

The study will be published April 1 in the journal Cell. The results identify both a mechanism and a potential therapy for drug tolerance that is induced in the TB bacteria by the host cells they infect.

Currently, TB treatment requires a complex, long-term curative regimen of at least six months, explained the senior author of the study, Dr. Lalita Ramakrishnan, University of Washington (UW) professor of medicine, microbiology and immunology. Her lab conducted the study in collaboration with Dr. Paul Edelstein, of the Department of Pathology and Laboratory Medicine at the University of Pennsylvania.

Many months of TB treatment are needed because the bacteria become tolerant to TB drugs. In the first couple days of treatment the bacteria die rapidly, but the death rate then slows to a crawl as the bacteria become resistant to killing. This tolerance to antibiotics occurs despite the absence of genetic mutations for drug resistance.

The authors noted that adhering to six months of drug treatment is difficult, particularly in areas of the world where TB is prevalent.

"Breaks in treatment can lead to relapses that perpetuate the TB epidemic and also fuel the development of genetic resistance to treatment," Edelstein said.

An urgent goal of scientists is to overcome drug tolerance, yet most of the drugs in development will not shorten the lengthy treatment. This failure results from a poor understanding of the mechanism of TB tolerance.

"Drug tolerance," Ramakrishnan said, "has been largely attributed to TB bacteria that are dormant in the body and not reproducing. These postulated dormant bacteria are thought to be unaffected by the administered antibiotics that are most effective against rapidly growing organisms"

In this latest study, the researchers draw another picture of what might be happening in TB. They described the existence of multi-drug tolerant organisms that form within days of infection in zebrafish, an animal model for studying TB. However, they were surprised to see this bacterial population actively growing and reproducing inside of host macrophages "big eater" white blood cells that engulf germs and debris in the body. In fact, the drug-tolerant bacteria not only thrive within these disease-fighting clean-up cells, but also co-opt them to carry the transiently drug resistant TB infection to other parts of the body. There they help promote its continuation inside of granulomas the nodules in the lung characteristic of TB.

To understand how growing bacteria might be tolerant to drugs, the authors turned to studying the human TB bacillus in human macrophages. They found that upon infecting macrophages, the bacteria deploy a structure called an efflux pump. The authors found that these pumps are essential for the TB bacteria to grow within macrophages and are turned on possibly to get rid of host antimicrobial substances targeted to penetrate the bacteria and destroy them.

Paradoxically it is the infected macrophage itself that stimulates the efflux pumps in the bacteria. The TB cell efflux pumps can also flush away medications, a mechanism, the researchers say, which may be contributing to multi-drug tolerance.

"Thus the TB drugs get caught in the crossfire in this pitched battle between bacterium and host," Ramakrishnan said.

Certain inexpensive medications are already available that can inhibit these bacterial pumps and thereby reduce multi-drug tolerance, the researchers noted. One of these is the calcium channel blocker verapamil, which is used to treat high blood pressure, angina, and some heart rhythm problems.

The researchers suggest that adding this currently approved drug to TB therapy, or working to develop drugs that more specifically block the bacterial efflux pumps in TB organisms, might reduce multi-drug tolerance. If so, efflux pump inhibitors might be able to shorten the duration of curative treatment for TB.


Contact: Leila Gray
University of Washington

Related medicine news :

1. Latest findings of Dartmouth HIV/AIDS study could turn treatment on its head
2. Research provides new findings on drug delivery with nanoparticles
3. SMFM highlights significance of spina bifida research findings
4. Most Guidelines for Infectious Diseases Dont Come From Clinical Trial Findings
5. International research team reports major findings in prevention and treatment of blood clots
6. VCU findings may help explain some major clinical symptoms of preeclampsia
7. Addiction research: Key findings every month
8. Encouraging findings suggest new avenues for treating liver disease in overweight Americans
9. Latest Findings Back Mammograms for Women in Their 40s
10. National committee releases findings on transforming and improving the nursing profession
11. Study findings show value of dietary supplement SAMe in treatment of adults with major depressive disorders
Post Your Comments:
Related Image:
New findings on drug tolerance in TB suggest ideas for shorter cures
(Date:6/25/2016)... Washington, D.C. (PRWEB) , ... June 25, 2016 ... ... will discuss health policy issues and applications at AcademyHealth’s Annual Research Meeting June ... share their work on several important health care topics including advance care planning, ...
(Date:6/25/2016)... Aliso Viejo, California (PRWEB) , ... June 25, 2016 , ... ... preset to fit their specific project," said Christina Austin - CEO of Pixel Film ... all fully customizable and all within Final Cut Pro X . Simply select ...
(Date:6/25/2016)... ... June 25, 2016 , ... ... recover from injury. Recently, he has implemented orthobiologic procedures as a method for ... is one of the first doctors to perform the treatment. Orthobiologics are substances ...
(Date:6/24/2016)... Los Angeles, CA (PRWEB) , ... June 24, 2016 , ... ... plastic surgery procedures that most people are unfamiliar with. The article goes on to ... known procedures, but also many of these less common operations such as calf and ...
(Date:6/24/2016)... ... ... crisis. Her son James, eight, was out of control. Prone to extreme mood shifts and ... him, he couldn’t control his emotions,” remembers Marcy. “If there was a knife on ... say he was going to kill them. If we were driving on the freeway, ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... 23, 2016 Any dentist who has made an ... current process. Many of them do not even offer this ... and high laboratory costs involved. And those who ARE able ... such a high cost that the majority of today,s patients ... Parsa Zadeh , founder of Dental Evolutions Inc. and ...
(Date:6/23/2016)... , June 23, 2016  In a startling report released ... failing their residents by lacking a comprehensive, proven plan to eliminate ... a definitive ranking of how states are tackling the worst drug ... only four states – Kentucky , ... Vermont . Of the 28 failing states, three – ...
(Date:6/23/2016)... Research and Markets has announced the ... 2016 - Forecast to 2022" report to their offering. ... up to date financial data derived from varied research sources ... with potential impact on the market during the next five ... comprises of sub markets, regional and country level analysis. The ...
Breaking Medicine Technology: