by Van den Kerkhof M, Leprohon P, Mabille D, Hendrickx S, Tulloch LB, Wall RJ, Wyllie S, Chatelain E, Mowbray CE, Braillard S, Ouellette M, Maes L, Caljon G. Microorganisms 2021; 9(7):1408. doi: 10.3390/microorganisms9071408
Summary: DNDI-6148 is an oxaborole under development for the treatment of visceral leishmaniasis. It is important to identify the Leishmania target(s) and additional resistance determinants of DNDI-6148 for its clinical development and possible selection of a partner drug for combination therapy. This study evaluated the likelihood of resistance emergence and found that prolonged exposure to DNDI-6148 (and back-up compound DNDI-5421) did not lead to the emergence of compound-resistant parasites. This study confirmed that these compounds do not share the efflux transporter-related resistance mechanism common to several antileishmanials. Screening of two overexpression libraries identified genes from chromosome 2 that provide a slight advantage under drug pressure, but additional studies are needed to investigate this further.