Variants, Art and Resistance

TB in TidBits: March 2021

Gene Variant tracking reveals insights

By tracing how a gene variant that makes people more vulnerable to tuberculosis evolved, researchers have been able to follow the rise and fall of the disease over the past 10,000 years. In the study, the gene variant's evolution that's making people susceptible to TB, the researchers discovered that the P1104A mutation was really old or ancient. By examining changes in how often the variant arose over time, the study investigators approximated that roughly three percent of the population carried the gene until roughly 5,000 years back.

Read More: Scientists Trace Evolution of Gene Variant That Makes People Vulnerable to Tuberculosis

The ART (for) preventing TB prevention

Antiretroviral treatment (ART) reduces the risk of developing active tuberculosis (TB) in people also infected with HIV-1, by dampening the activation of the body's immune response. These findings could help improve treatment for both conditions in the future. Robert Wilkinson, Group Leader of the Crick's tuberculosis laboratory, said: "Our increased understanding of TB in people who also have HIV, could lead to improved treatments for both conditions. "Long term dysregulation of the immune system can be damaging to many parts of the body, so treatments of the future should aim to tackle this so that we can effectively control TB and HIV with fewer side effects for people."

Read More: HIV treatment helps prevent active TB

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Targeting Resistance

Unique drug target vs resistance

Researchers have identified a critical mechanism that allows deadly bacteria to gain resistance to antibiotics. The findings offer a potential new drug target in the search for effective new antibiotics as we face the growing threat of antimicrobial resistance (AMR) and infections caused by bacterial pathogens. The study investigated quinolone antibiotics which are used to treat a range of bacterial infections, including TB (tuberculosis). Quinolones work by inhibiting bacterial enzymes, gyrase, and topoisomerase IV, thereby preventing DNA replication and RNA synthesis essential to growth. In this study, John Innes Centre researchers in the group of professor Tony Maxwell set out to discover how PRPs such as MfpA, work at the molecular level. They purified MfpA from Mycobacterium smegmatis, a close relative of M. tuberculosis, and showed that it can inhibit the supercoiling reaction of DNA gyrase, the target of quinolones in TB causing mycobacteria.

Read More: Research Pinpoints Unique Drug Target in Antibiotic-resistant Bacteria

An old ally to counter resistance

Rockefeller scientists have landed on an existing compound, naturally produced by a bacterium. Their research, published in the Proceedings of the National Academy of Sciences, elucidates how sorangicin A, first discovered in the 1980s, can destroy even the antibiotic-resistant bacteria that cause tuberculosis. The findings suggest that the compound may be a good candidate for further development as a first-line antibiotic for tuberculosis. “Sorangicin inhibits regular strains in very much the same way as rifampin, one of the primary choices for tuberculosis antibiotics. But now we show that, through a different mechanism, it also traps those variants that escape rifampin,” says Elizabeth Campbell, a research associate professor at Rockefeller.

Read More: An old antibiotic may combat drug-resistant tuberculosis

TB diagnosis kits in developing nations

LAMP: 1 dollar, 1 hour

Developing reasonably priced, easy-to-use diagnosis kits that can swiftly and accurately detect infectious diseases in developing countries has become the main mission of Chie Nakajima and Kyoko Hayashida, as they seek to alleviate some of the hardship endured by poverty-stricken people. Nakajima is developing diagnosis kits to detect TB, which causes over 4,000 deaths daily worldwide. Her main target now is multidrug-resistant (MDR) TB that does not respond to at least isoniazid and rifampin, two powerful anti-TB medications.

To address these problems, Hayashida and Nakajima have developed a new diagnostic kit based on a loop-mediated isothermal amplification (LAMP) system, a nucleic acid amplification test method originally developed by Eiken Chemical Co., Ltd. "With our new system called CZC-LAMP, we only need a drop of blood to test for the infection. It costs less than one U.S. dollar per test and the result can be obtained within one hour without the use of sophisticated equipment," says Hayashida. They substantially modified the LAMP system to allow on-site diagnosis even in remote areas.

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