Optimization and utilization of single chain metallocatanionic vesicles for antibacterial photodynamic therapy (aPDT) againstE. coli
JOURNAL OF MATERIALS CHEMISTRY B
Authors: Sharma, Bunty; Kaur, Gurpreet; Chaudhary, Ganga Ram
Currently, bacterial infection due to multi-drug-resistant bacteria is one of the foremost problems in public health. Photodynamic therapy plays a significant role against bacterial infection, without causing any side effects. But the photosensitizers are associated with many drawbacks, which lessen their photodynamic efficiency. In this context, the current study describes the synthesis of new metallocatanionic vesicles and employs them in photodynamic therapy. These vesicles were synthesized by using a single-chain cationic metallosurfactant (CuCPC I) and sodium oleate (NaOl) as an anionic component. These vesicles were characterized from conductivity, dynamic light scattering, zeta potential, field emission scanning electron microscopy, and confocal microscopy measurements. Methylene blue (MB) was used as a photosensitizer and its singlet oxygen quantum yield in the presence of these vesicles was determined by irradiating with 650 nm wavelength laser light. These vesicles play a dual-functional role, one helping in delivering the photosensitizer and the second doubling their singlet oxygen production capability due to the presence of metal ions. Antibacterial photodynamic therapy (aPDT) was studied againstE. colibacteria (Gram-negative bacteria). These vesicles also inherit their antibacterial activity and MB-encapsulated metallocatanionic vesicles on irradiation have shown 100% killing efficiency. In summary, we offer metallocatanionic vesicles preparedviaa facile approach, which encapsulate a photosensitizer and can be used to combatE. coliinfection through photodynamic therapy. We envisage that these synthesized metallocatanionic vesicles will provide a new modification to the catanionic mixture family and could be used for various applications in the future.
Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin
Authors: Sun, Hongzhe; Zhang, Qi; Wang, Runming; Wang, Haibo; Wong, Yuen-Ting; Wang, Minji; Hao, Quan; Yan, Aixin; Kao, Richard Yi-Tsun; Ho, Pak-Leung; Li, Hongyan
Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, bla(MBL) and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-beta -lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of beta -lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-beta -lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs. Multi-drug resistant pathogens remain a serious public health threat. Here, Sun and colleagues identify a role for auranofin, which is normally used as a drug for rheumatoid arthritis, for reversing antibiotic resistance to carbapenem and colistin.