Lanni, A.; Iacobino, A.; Fattorini, L.; Giannoni, F. Eradication of Drug-Tolerant Mycobacterium tuberculosis 2022: Where We Stand. Microorganisms2023, 11, 1511.
Lanni, A.; Iacobino, A.; Fattorini, L.; Giannoni, F. Eradication of Drug-Tolerant Mycobacterium tuberculosis 2022: Where We Stand. Microorganisms 2023, 11, 1511.
Lanni, A.; Iacobino, A.; Fattorini, L.; Giannoni, F. Eradication of Drug-Tolerant Mycobacterium tuberculosis 2022: Where We Stand. Microorganisms2023, 11, 1511.
Lanni, A.; Iacobino, A.; Fattorini, L.; Giannoni, F. Eradication of Drug-Tolerant Mycobacterium tuberculosis 2022: Where We Stand. Microorganisms 2023, 11, 1511.
Abstract
The lungs of tuberculosis (TB) patients contain a spectrum of granulomatous lesions ranging from solid and well vascularized cellular granulomas, to avascular caseous granulomas. In solid granulomas, current therapy kills actively replicating (AR) intracellular bacilli, while in low vascularized caseous granulomas the low oxygen tension stimulates aerobic and microaerophilic AR bacilli to transit into non-replicating (NR), drug-tolerant, extracellular stages. These stages, which do not have genetic mutations and are often referred to as persisters, are difficult to eradicate due to low drug penetration inside caseum and mycobacterial cell walls. The sputum of TB patients contains also viable bacilli called differentially detectable (DD) cells that, unlike persisters, grow in liquid, but not in solid media. This review provides a comprehensive update on drug combinations killing in vitro AR and drug-tolerant bacilli (persisters and DD cells), and sterilizing Mycobacterium tuberculosis-infected BALB/c and caseum-forming C3HeB/FeJ mice. These observations have been important for testing new drug combinations in noninferiority clinical trials, in order to shorten duration of current regimens against TB. In 2022, the World Health Organization, based on one of this trial, supported the use of a 4-month regimen for treatment of drug-susceptible TB as a possible alternative to the current 6-month regimen.
Biology and Life Sciences, Immunology and Microbiology
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