Antimicrobial Action of Chelating Agents: Repercussions on the Microorganism Development, Virulence and Pathogenesis

Abstract

Infections caused by resistant microorganisms often fail to respond to conventional therapy, resulting in prolonged illness, increased treatment costs and greater risk of death. Consequently, the development of novel antimicrobial drugs is becoming more demanding every day since the existing drugs either have too many side-effects or they tend to lose effectiveness due to the selection of resistant strains. In view of these facts, a number of new strategies to obstruct vital biological processes of a microbial cell have emerged; one of these is focused on the use of metal-chelating agents, which are able to selectively disturb the essential metal metabolism of the microorganism by interfering with metal acquisition and bioavailability for crucial reactions. The chelation activity is able to inhibit the biological role of metal-dependent proteins (e.g., metalloproteases and transcription factors), disturbing the microbial cell homeostasis and culminating in the blockage of microbial nutrition, growth and development, cellular differentiation, adhesion to biotic (e.g., extracellular matrix components, cell and/or tissue) and abiotic (e.g., plastic, silicone and acrylic) structures as well as controlling the in vivo infection progression. Interestingly, chelating agents also potentiate the activity of classical antimicrobial compounds. The differences between the microorganism and host in terms of the behavior displayed in the presence of chelating agents could provide exploitable targets for the development of an effective chemotherapy for these diseases. Consequently, metal chelators represent a novel group of antimicrobial agents with potential therapeutic applications. This review will focus on the anti-fungal and anti-protozoan action of the most common chelating agents, deciphering and discussing their mode of action.

Matrix Metalloproteinase Inhibitor as an Antimicrobial Agent to Eradicate Enterococcus faecalis Biofilm

“…In fact, this compound has been shown to inhibit the growth of Mycobacterium (20) and Candida (18,19). The mechanism of its antimicrobial properties appears to be related to its ability to selectively disturb essential trace metals required for bacterial metabolism (15,19,21). This compound contains 3 fused benzene rings with o-quinoid moiety and forms strong complexes with transition metal ions at the N-N terminal, with preponderance toward Zn 2+ and to a lesser extent for Fe 2+ , Ca 2+ , Cu 2+ , Co 2+ , and Mn 2+ (19).…”

“…When MMPs in microbial cells are inhibited, microbial cell homeostasis is disrupted, and growth is retarded (15). MMPs are also present in dentin, and when liberated during resin-based restorative procedures, they could compromise the integrity of the hybrid layer interface and adversely affect the seal provided by resin-based restorative materials (16).…”

“…The metal chelator 1,10-phenanthroline-5,6-dione (Phendione) functions as an MMP inhibitor through its ability to chelate metal ions, which are essential for the enzymatic activities of MMPs (15,(17)(18)(19). In this study, Phendione as a potentially novel antimicrobial agent against E. faecalis and its effect on human MMP-2 were investigated.…”

Exploring the thiazole scaffold for the identification of new agents for the treatment of fluconazole resistant Candida

“…The efficacy and selectivity of azoles depends on the strength of the binding to heme iron as well as the affinity of the N-1 substituent for the CYP51 17 . It has been reported that the presence of iron chelators influences the growth of C. albicans 18,19 . In this respect, thiosemicarbazones iron chelators have been reported as antifungal agents and their activity compared with that of FLC 20 .…”

Pirometamorfismo ígneo na Bacia Potiguar, Nordeste do Brasil

“…Apesar das intrusões serem conhecidas há décadas (Sial, 1976), apenas recentemente têm sido feitas referências sobre efeitos termais provocados nas encaixantes sedimentares (Paiva, 2004;Silveira, 2006;Sousa et al, 2008). Santos (2011), Santos et al (2011Santos et al ( , 2012 e Souza et al (2011) aplicaram o termo buchito a rochas na fácies sanidinito, resultantes de fusão parcial da matriz feldspática de arenitos da Formação Açu. O presente estudo abrange esta formação, principal unidade reservatório da Bacia Potiguar na porção onshore.…”