Is the Drug-tolerant Tuberculosis Possibly Behind TB Relapses?

University of Pittsburgh-led researchers have found a possible reason why human tuberculosis (TB) requires months of intensive antibiotic treatment, as well as a potential cause of the relapses that can nonetheless occur.

They have discovered that the primary bacteria behind tuberculosis can grow on surfaces and that drug-tolerant strains flourish in these bacterial communities.

Senior author Graham Hatfull, chair and Eberly Family Professor of Biological Sciences in Pitt's School of Arts and Sciences, said that his team is first one to show that 'Mycobacterium tuberculosis' can grow in surface-level bacteria clusters known as biofilms that are common in nature but never before shown for TB bacteria.

Hatfull collaborated and coauthored the paper with Professor William Jacobs Jr. of the Department of Microbiology and Immunology at the Albert Einstein College of Medicine in New York.

Hatfull, Jacobs, and their colleagues found that the biofilm bacteria are physiologically and genetically different from TB bacteria harvested in a lab-the type used in developing antibiotics.

These variations result in a population of the bacteria that are 'drug-tolerant and harbor persistent cells that survive high concentrations of anti-tuberculosis antibiotics.'

People with TB typically undergo six to nine months of treatment with multiple antibiotics and most of the bacteria generally die within the first two weeks.

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Yet the disease can recur, presumably because of drug-tolerant bacteria that have escaped the antibiotic.

Jacobs said that the source and location of these persistent cells are unknown, but the new research reveals a possible biofilm origin.

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"The nature of persisting "M. tuberculosis" cells has been an enigma for the entire field. Clearly "M. tuberculosis" cells in biofilms represent at least one class of persistent cells, and we are testing their biological relevance," Jacobs said.

Hatfull said that it is not yet known whether the biofilm actually factors into human TB infections.

He added that the only similar research regarding biofilm in living creatures showed the presence of biofilm-like or biofilm-related bacteria in guinea pigs.

"While our data does not show conclusively that biofilm formation in people gives rise to a drug-tolerant population, the fact that biofilms do so in the lab makes this an interesting and testable hypothesis," Hatfull said.

The research has been reported in 'Molecular Microbiology.'

Source-ANI
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