Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity

Frei, Angelo; King, Anna; Lowe, Gabrielle J.; Cain, Amy K.; Short, Francesca L.; Dinh, Hue; Elliott, Alysha G.; Zuegg, Johannes; Wilson, Justin J.; Blaskovich, Mark A. T.

doi:10.1002/chem.202003545

Cited by 40 publications

(36 citation statements)

References 42 publications

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“…Following a protocol previously reported by us we used larvae of the greater wax moth Galleria mellonella as a model organism for in vivo toxicity and efficacy [20] . This low‐cost animal model provides good quality data on both toxicity and efficacy of antimicrobial compounds that has been shown to correlate well with results obtained in more expensive and ethically more demanding mouse models [21] .…”

Section: Resultsmentioning

confidence: 99%

Platinum Cyclooctadiene Complexes with Activity against Gram‐positive Bacteria

et al. 2021

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Antimicrobial resistance is a looming health crisis, and it is becoming increasingly clear that organic chemistry alone is not sufficient to continue to provide the world with novel and effective antibiotics. Recently there has been an increased number of reports describing promising antimicrobial properties of metal‐containing compounds. Platinum complexes are well known in the field of inorganic medicinal chemistry for their tremendous success as anticancer agents. Here we report on the promising antibacterial properties of platinum cyclooctadiene (COD) complexes. Amongst the 15 compounds studied, the simplest compounds Pt(COD)X2 (X=Cl, I, Pt1 and Pt2) showed excellent activity against a panel of Gram‐positive bacteria including vancomycin and methicillin resistant Staphylococcus aureus. Additionally, the lead compounds show no toxicity against mammalian cells or haemolytic properties at the highest tested concentrations, indicating that the observed activity is specific against bacteria. Finally, these compounds showed no toxicity against Galleria mellonella at the highest measured concentrations. However, preliminary efficacy studies in the same animal model found no decrease in bacterial load upon treatment with Pt1 and Pt2. Serum exchange studies suggest that these compounds exhibit high serum binding which reduces their bioavailability in vivo, mandating alternative administration routes such as e. g. topical application.

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Section: Resultsmentioning

confidence: 99%

Platinum Cyclooctadiene Complexes with Activity against Gram‐positive Bacteria

et al. 2021

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“…Thus, we attempted to figure out the in vivo toxicity and antifungal activity of ZnO-NPs. Galleria mellonella larvae have been widely used as an animal model to study the pathogenesis of microorganisms and assess the antimicrobial activity of new compounds (Frei et al, 2021). In addition, some research extended the utilization of larvae to study NPs (Moya-Anderico et al, 2021a,b).…”

Section: Discussionmentioning

confidence: 99%

Zinc Oxide Nanoparticles Prime a Protective Immune Response in Galleria mellonella to Defend Against Candida albicans

Pan

et al. 2021

Front. Microbiol.

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Purpose: Zinc oxide nanoparticles (ZnO-NPs) have exerted antimicrobial properties. However, there is insufficient evaluation regarding the in vivo antifungal activity of ZnO-NPs. This study aimed to investigate the efficacy and mechanism of ZnO-NPs in controlling Candida albicans in the invertebrate Galleria mellonella.Methods:Galleria mellonella larvae were injected with different doses of ZnO-NPs to determine their in vivo toxicity. Non-toxic doses of ZnO-NPs were chosen for prophylactic injection in G. mellonella followed by C. albicans infection. Then the direct in vitro antifungal effect of ZnO-NPs against C. albicans was evaluated. In addition, the mode of action of ZnO-NPs was assessed in larvae through different assays: quantification of hemocyte density, morphology observation of hemocytes, characterization of hemocyte aggregation and phagocytosis, and measurement of hemolymph phenoloxidase (PO) activity.Results: Zinc oxide nanoparticles were non-toxic to the larvae at relatively low concentrations (≤20 mg/kg). ZnO-NP pretreatment significantly prolonged the survival of C. albicans-infected larvae and decreased the fungal dissemination and burden in the C. albicans-infected larvae. This observation was more related to the activation of host defense rather than their fungicidal capacities. Specifically, ZnO-NP treatment increased hemocyte density, promoted hemocyte aggregation, enhanced hemocyte phagocytosis, and activated PO activity in larvae.Conclusion: Prophylactic treatment with lower concentrations of ZnO-NPs protects G. mellonella from C. albicans infection. The innate immune response primed by ZnO-NPs may be part of the reason for the protective effects. This study provides new evidence of the capacity of ZnO-NPs in enhancing host immunity and predicts that ZnO-NPs will be attractive for further anti-infection applications.

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“…The Galleria mellonella infection experiments were performed as previously described in [ 60 ]. Briefly, triplicate assays of five larvae (200–230 mg) were injected with 1×10 7 A. baumannii cells from the six environmental and four clinical strains separately.…”

Section: Methodsmentioning

confidence: 99%

Genomic and phenotypic analyses of diverse non-clinical Acinetobacter baumannii strains reveals strain-specific virulence and resistance capacity

et al. 2022

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Acinetobacter baumannii is a critically important pathogen known for its widespread antibiotic resistance and ability to persist in hospital-associated environments. Whilst the majority of A. baumannii infections are hospital-acquired, infections from outside the hospital have been reported with high mortality. Despite this, little is known about the natural environmental reservoir(s) of A. baumannii and the virulence potential underlying non-clinical strains. Here, we report the complete genome sequences of six diverse strains isolated from environments such as river, soil, and industrial sites around the world. Phylogenetic analyses showed that four of these strains were unrelated to representative nosocomial strains and do not share a monophyletic origin, whereas two had sequence types belonging to the global clone lineages GC1 and GC2. Further, the majority of these strains harboured genes linked to virulence and stress protection in nosocomial strains. These genotypic properties correlated well with in vitro virulence phenotypic assays testing resistance to abiotic stresses, serum survival, and capsule formation. Virulence potential was confirmed in vivo, with most environmental strains able to effectively kill Galleria mellonella greater wax moth larvae. Using phenomic arrays and antibiotic resistance profiling, environmental and nosocomial strains were shown to have similar substrate utilisation patterns although environmental strains were distinctly more sensitive to antibiotics. Taken together, these features of environmental A. baumannii strains suggest the existence of a strain-specific distinct gene pools for niche specific adaptation. Furthermore, environmental strains appear to be equally virulent as contemporary nosocomial strains but remain largely antibiotic sensitive.

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Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity

Cited by 40 publications

References 42 publications

Platinum Cyclooctadiene Complexes with Activity against Gram‐positive Bacteria

Platinum Cyclooctadiene Complexes with Activity against Gram‐positive Bacteria

Zinc Oxide Nanoparticles Prime a Protective Immune Response in Galleria mellonella to Defend Against Candida albicans

Genomic and phenotypic analyses of diverse non-clinical Acinetobacter baumannii strains reveals strain-specific virulence and resistance capacity

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