Telacebec is an emerging antibiotic. It’s part of a new class of antibiotics that disrupt the electron transport chain, which could be used to treat drug-resistant tuberculosis. Telacebec also has the potential to treat diseases closely related to tuberculosis, such as leprosy and Buruli ulcer. The Buruli ulcer pathogen, Mycobacterium ulcerans, is especially sensitive to telacebec.
Buruli Ulcer
Buruli ulcer is a neglected tropical disease that causes open wounds on the arms and legs. The standard of care is an eight-week-long course of antibiotics, which is difficult to give in resource-poor settings. Recently, a research team wanted to see if telacebec could be used as a shorter treatment.
Experimental Model
They infected mouse footpads with Mycobacterium ulcerans, then gave the mice a range of doses of telacebec. These treatments were more effective than standard antibiotics, and cleared infection after five days of treatment, or even in some cases after a single dose.
Mouse footpads continued to improve even after the treatment was stopped. We know that Mycobacterium ulcerans knocks down the immune system in infected limbs. Telacebec treatment might restore the immune system, which then clears the infection. To test this hypothesis, the researchers repeated their experiment in immunocompromised mice. These mice didn’t respond to treatment as well as normal mice.
A Word of Caution
Telacebec shows great promise for improving the treatment of Buruli ulcer, but short course, monotherapy treatments such as this one risk causing antibiotic resistance. Furthermore, doctors should use extra care with immunocompromised patients, such as people with HIV. For these people it might be safer to use a longer course of treatment or to use telacebec as part of an antibiotic cocktail.
Komm O, Almeida DV, Converse PJ, et al. Impact of dose, duration, and immune status on efficacy of ultrashort telacebec regimens in mouse models of Buruli ulcer. Antimicrobial Agents Chemotherapy. 2021 Oct 18,65(11):e0141821. doi: 10.1128/AAC.01418-21 PMID: 34460302