title: 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.
authors.affiliation: Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. alsouzasantos@gmail.com
authors.forename: A L S
authors.initials: AL
authors.lastname: Santos
authors.forename: C L
authors.initials: CL
authors.lastname: Sodre
authors.forename: R S
authors.initials: RS
authors.lastname: Valle
authors.forename: B A
authors.initials: BA
authors.lastname: Silva
authors.forename: E A
authors.initials: EA
authors.lastname: Abi-Chacra
authors.forename: L V
authors.initials: LV
authors.lastname: Silva
authors.forename: A L
authors.initials: AL
authors.lastname: Souza-Goncalves
authors.forename: L S
authors.initials: LS
authors.lastname: Sangenito
authors.forename: D S
authors.initials: DS
authors.lastname: Goncalves
authors.forename: L O P
authors.initials: LO
authors.lastname: Souza
authors.forename: V F
authors.initials: VF
authors.lastname: Palmeira
authors.forename: C M
authors.initials: CM
authors.lastname: d'Avila-Levy
authors.forename: L F
authors.initials: LF
authors.lastname: Kneipp
authors.forename: A
authors.initials: A
authors.lastname: Kellett
authors.forename: M
authors.initials: M
authors.lastname: McCann
authors.forename: M H
authors.initials: MH
authors.lastname: Branquinha
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D010961:Plasmodium / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity; D014345:Trypanosoma / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity
chemical_list: D000890:Anti-Infective Agents; D000981:Antiprotozoal Agents; D002614:Chelating Agents