Drug resistance in topoisomerase-targeting therapy

Topoisomerase targeting with and resistance to gemifloxacin in Staphylococcus aureus.

Gemifloxacin, a novel quinolone with potent activity against Staphylococcus aureus, was 8- to 16-fold more active against wild-type S. aureus than ciprofloxacin. The two- to fourfold increase in the MIC of gemifloxacin in genetically defined grlBA mutants and the twofold increase in a single gyrA mutant, supported by the low frequency of selection of resistant mutants at twice the MIC (7.4 x 10...

Drug targeting of leptin resistance.

Leptin regulates glucose, lipid and energy homeostasis as well as feeding behavior, serving as a bridge between peripheral metabolically active tissues and the central nervous system (CNS). Indeed, this adipocyte-derived hormone, whose circulating levels mirror fat mass, not only exerts its anti-obesity effects mainly modulating the activity of specific hypothalamic neurons expressing the long ...

Targeting Drug Resistance Mechanisms in Mycobacterium tuberculosis

Historically, tuberculosis (TB) has left a scar as mankind’s greatest infectious killer. With evidence of TB infection dating back nine millenia to a Neolithic Eastern Mediterranean settlement [1], this ancient disease meant almost certain death to those infected, a phenomenon spanning pre-antibiotic eras from the time of the Roman empire all the way to the beginning of the 20th century. But wi...

Drug Resistance in Antimicrobial Therapy

Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis

African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In c...