Metal‐based antimicrobial strategies against intramacrophage<i>Mycobacterium tuberculosis</i>

Coelho, Tatiane S.; Halicki, Priscila Cristina Bartolomeu; Silva, L.; Vicenti, Juliano Rosa de Menezes; Gonçalves, Bruna Lisboa; Silva, P.E. Almeida da; Ramos, Daniela Fernandes

doi:10.1111/lam.13298

Cited by 12 publications

(5 citation statements)

References 44 publications

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“…Very recent promising results have been obtained by a novel class of Cu and Co compounds containing benzohydroxamate as a ligand: the investigated compounds interact with the enzyme urease, which is crucial for the bacillus survival in the intraphagosomal environment [127].…”

Section: Antibiotic Metal Complexes In Mtb Treatmentmentioning

confidence: 99%

Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

Natale

Benedictis

et al. 2020

Antibiotics

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In metal-peptide interactions, cations form stable complexes through bonds with coordinating groups as side chains of amino acids. These compounds, among other things, exert a wide variety of antimicrobial activities through structural changes of peptides upon metal binding and redox chemistry. They exhibit different mechanisms of action (MOA), including the modification of DNA/RNA, protein and cell wall synthesis, permeabilization and modulation of gradients of cellular membranes. Nowadays, the large increase in antibiotic resistance represents a crucial problem to limit progression at the pandemic level of the diseases that seemed nearly eradicated, such as tuberculosis (Tb). Mycobacterium tuberculosis (Mtb) is intrinsically resistant to many antibiotics due to chromosomal mutations which can lead to the onset of novel strains. Consequently, the maximum pharmaceutical effort should be focused on the development of new therapeutic agents and antimicrobial peptides can represent a valuable option as a copious source of potential bioactive compounds. The introduction of a metal center can improve chemical diversity and hence specificity and bioavailability while, in turn, the coordination to peptides of metal complexes can protect them and enhance their poor water solubility and air stability: the optimization of these parameters is strictly required for drug prioritization and to obtain potent inhibitors of Mtb infections with novel MOAs. Here, we present a panoramic review of the most recent findings in the field of metal complex-peptide conjugates and their delivery systems with the potential pharmaceutical application as novel antibiotics in Mtb infections.

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Section: Antibiotic Metal Complexes In Mtb Treatmentmentioning

confidence: 99%

Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

Natale

Benedictis

et al. 2020

Antibiotics

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“…Moreover, the use of transition metals as Cu 2+ and Co 2+ associated with benzohydroxamate showed good results against intracellular M. tuberculosis ( Figure 1 A). However, further research is required to understand their mechanisms of action and to discard any cytotoxic effects on human cells [ 23 ].…”

Section: Repurposing Anti-infectives Against M Tuberculmentioning

confidence: 99%

Novel Treatments against Mycobacterium tuberculosis Based on Drug Repurposing

et al. 2020

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Tuberculosis is the leading cause of death, worldwide, due to a bacterial pathogen. This respiratory disease is caused by the intracellular pathogen Mycobacterium tuberculosis and produces 1.5 million deaths every year. The incidence of tuberculosis has decreased during the last decade, but the emergence of MultiDrug-Resistant (MDR-TB) and Extensively Drug-Resistant (XDR-TB) strains of M. tuberculosis is generating a new health alarm. Therefore, the development of novel therapies based on repurposed drugs against MDR-TB and XDR-TB have recently gathered significant interest. Recent evidence, focused on the role of host molecular factors on M. tuberculosis intracellular survival, allowed the identification of new host-directed therapies. Interestingly, the mechanism of action of many of these therapies is linked to the activation of autophagy (e.g., nitazoxanide or imatinib) and other well-known molecular pathways such as apoptosis (e.g., cisplatin and calycopterin). Here, we review the latest developments on the identification of novel antimicrobials against tuberculosis (including avermectins, eltrombopag, or fluvastatin), new host-targeting therapies (e.g., corticoids, fosfamatinib or carfilzomib) and the host molecular factors required for a mycobacterial infection that could be promising targets for future drug development.

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“…Ion-exchanged nanozeolites (IE-nZeos) and GPs strategically exploit ion release and adsorptive capacities for leveraging topical therapeutic applications with site-directed antimicrobial delivery and bacterial and toxin adsorption, respectively, as we previously demonstrated (21)(22)(23). Metal ions with previously reported antimicrobial properties, such as copper and silver (16,25), can be interchangeably attached to the extensive nZeos surface, enabling subsequent ion exchange with water or moisture and dispersion of metal ions from the scaffold into the environment (22,23,26).…”

Section: Introductionmentioning

confidence: 99%

“…Mycobacterium marinum (Mmar), the closest genetic relative of MU and a fast-growing nontuberculous mycobacterium SSTI pathogen (27-30), causes non-ulcerative granulomatous skin lesions that are often linked with fish aquaria (31) or fishing-related injuries (32). As a close relative of both MU and Mycobacterium tuberculosis (33), Mmar provides context to decades of research focused on iondependent antimicrobial activity against mycobacteria (25,34,35). Silver nanoparticles exhibit antimicrobial activity against Mmar (35), whereas silver enriched dressings (36,37) and copper-rich clay materials (16) kill MU.…”

Section: Introductionmentioning

confidence: 99%

Modified aluminosilicates display antibacterial activity against nontuberculous mycobacteria and adsorb mycolactone and Mycobacterium ulcerans in vitro

Dermody

Ali²,

Popovich³

et al. 2022

Front. Trop. Dis

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Mycobacterium ulcerans (MU) infection of skin and soft tissue leads to chronic skin ulceration known as Buruli ulcer. MU releases a lipid-like toxin, mycolactone, that diffuses into the tissue, effecting disease through localized tissue necrosis and immunosuppression. Cutaneous Buruli ulcer wounds slowly advance from a painless pre-ulcerative stage to an ulcerative lesion, leading to disparities in the timing of medical intervention and treatment outcomes. Novel Buruli ulcer wound management solutions could complement and supplement systemically administered antimicrobials and reduce time to healing. Capitalizing on nanopore structure, adsorption, and exchange capacities, aluminosilicate nanozeolites (nZeos) and geopolymers (GPs) were developed and investigated in the context of therapeutics for mycobacterial disease ulcerative wound care. nZeos were ion exchanged with copper or silver to assess the antimicrobial activity against MU and Mycobacterium marinum, a rapid growing, genetic ancestor of MU that also causes skin and soft tissue infections. Silver- and copper-exchanged nZeos were bactericidal against MU, while only silver-exchanged nZeos killed M. marinum. To mediate adsorption at a biological scale, GPs with different pore sizes and altered surface modifications were generated and assessed for the ability to adsorb MU and mycolactone. Macroporous GPs with and without stearic acid modification equivalently adsorbed MU cells, while mesoporous GPs with stearic acid adsorbed mycolactone toxin significantly better than mesoporous GPs or GPs modified with phenyltriethoxysilane (PTES). In cytotoxicity assays, Cu-nZeos lacked toxicity against Detroit 551, U-937, and WM-115 cells. GPs demonstrated limited cytotoxicity in Detroit 551 and WM-115, but produced time-dependent toxicity in U-937 cells. With their large surface area and adsorptive capacities, aluminosilicates nZeos and GPs may be modified and developed to support conventional BU wound care. Topical application of nZeos and GPs could kill MU within the cutaneous wound environment and physically remove MU and mycolactone with wound dressing changes, thereby improving wound healing and overall patient outcomes.

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Metal‐based antimicrobial strategies against intramacrophageMycobacterium tuberculosis

Cited by 12 publications

References 44 publications

Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

Novel Treatments against Mycobacterium tuberculosis Based on Drug Repurposing

Modified aluminosilicates display antibacterial activity against nontuberculous mycobacteria and adsorb mycolactone and Mycobacterium ulcerans in vitro

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