Abstract
BackgroundAlternative treatment strategies have become essential in overcoming the problem of drug-resistant Mycobacterium tuberculosis (Mtb). In this preliminary in vitro study, the anti-tuberculosis (anti-TB) activity of exogenous iron chelators (xenosiderophores) such as Exochelin-MS (Exo-MS) and Deferoxamine-B (DFO-B) was evaluated against ten multi-drug-resistant (MDR) and seven pyrazinamide-resistant (PZAR) Mtb isolates.MethodsMycobacteria Growth Indicator Tube-Drug Susceptibility Test was used to assess the anti-TB effect of Exo-MS or DFO-B individually and their combinations with isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA).ResultsFor the MDR-Mtb isolates, Exo-MS alone inhibited two out of the five isolates tested. Whereas, DFO-B alone inhibited nine out of the ten MDR isolates tested. For PZA-resistant Mtb isolates, both Exo-MS and DFO-B individually inhibited five out of the seven isolates. The MIC of Exo-MS in combination with INH, RIF and PZA remained the same. The MIC of DFO-B decreased when tested in combination with INH, RIF and PZA.ConclusionsExo-MS and DFO-B were shown to have activity against drug-resistant Mtb isolates. Therefore, these xenosiderophores may be useful adjuncts to antibiotics in overcoming the problem of drug-resistant Mtb in clinical setting.
Highlights
Alternative treatment strategies have become essential in overcoming the problem of drug-resistant Mycobacterium tuberculosis (Mtb)
Infections caused by TB bacteria are usually treated with the firstline antituberculosis drugs, namely, isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), and streptomycin (STR)
Mtb bacteria have acquired resistance over the years to many of these drugs due to inappropriate use, mutations in Mtb, etc. These factors have resulted in the emergence of multi-drug-resistant TB (MDR-TB) and extensively-drug-resistant TB (XDR-TB), which have rendered current treatment strategies ineffective
Summary
Alternative treatment strategies have become essential in overcoming the problem of drug-resistant Mycobacterium tuberculosis (Mtb). In this preliminary in vitro study, the anti-tuberculosis (anti-TB) activity of exogenous iron chelators (xenosiderophores) such as Exochelin-MS (Exo-MS) and Deferoxamine-B (DFO-B) was evaluated against ten multi-drug-resistant (MDR) and seven pyrazinamide-resistant (PZAR) Mtb isolates. Mtb bacteria have acquired resistance over the years to many of these drugs due to inappropriate use, mutations in Mtb, etc. These factors have resulted in the emergence of multi-drug-resistant TB (MDR-TB) and extensively-drug-resistant TB (XDR-TB), which have rendered current treatment strategies ineffective.
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