ABSTRACT
Rapidly emerging drug-resistant superbugs, especially Gram-negative bacteria, pose a serious threat to healthcare systems all over the globe. Newer strategies are being developed to detect and overcome the arsenal of weapons that these bacteria possess. The development of antibiotics is time-consuming and may not provide full proof of action on evolving drug-resistant pathogens. The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) systems are promising in curbing drug-resistant bacteria. This review focuses on the pathogenesis of Gram-negative bacteria, emergence of antimicrobial drug resistance, and their treatment failures. It also draws attention to the present status of the CRISPR-Cas system in diagnosisand treatment of Gram-negative bacterial infections.
ABSTRACT
Infections by drug-resistant bacteria are life-threatening. As iron is a vital element for the growth of bacteria, iron-chelating agents (siderophores) can be used to arrest their multiplication. Exogenous siderophores - exochelin-MS and deferoxamine-B - were evaluated for their inhibitory activity against methicillin-resistant Staphylococcus aureus and metallo-ß-lactamase producers - Pseudomonas aeruginosa and Acinetobacter baumannii - by disc diffusion, micro-broth dilution, and turbidimetric growth assays. The drug-resistant isolates were inhibited by the synergistic activity of siderophores and antibiotics. Minimum inhibitory concentration of exochelin-MS+ampicillin for different isolates was between 0.05 and 0.5 mg/mL. Minimum inhibitory concentration of deferoxamine-B+ampicillin was 1.0 mg/mL and greater. Iron-chelation therapy could provide a complementary approach to overcome drug resistance in pathogenic bacteria.
ABSTRACT
BACKGROUND: Iron is a vital nutrient for all cells, and malignant cells have a higher requirement for the metal due to their rapid multiplication. Bacterial siderophores can be used to reduce free ferric ion concentration from the cellular environment. METHODS: In the present study, we have evaluated effect of three siderophores - exochelin-MS, mycobactin S and deferoxamine B on the proliferation of mammalian cell lines using MTT assay. RESULTS: These siderophores caused a significant decrease in the viability of malignant cells, without significantly affecting non-malignant cells. CONCLUSIONS: Based on these results, we suggest that iron-chelation therapy could be explored as an adjunctive therapeutic option against cancer along with other therapies.
Subject(s)
Cell Proliferation/drug effects , Siderophores/pharmacology , Animals , Cell Line, Tumor , Deferoxamine/pharmacology , Humans , Mice , Oxazoles/pharmacology , Peptides, Cyclic/pharmacologyABSTRACT
BACKGROUND: 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 (PZA R ) Mtb isolates. METHODS: Mycobacteria 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). RESULTS: For 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. CONCLUSIONS: Exo-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.
