ABSTRACT
The abuse and incorrect administration of antibiotics has resulted in an increased proliferation of bacteria that exhibit drug resistance. The emergence of resistant bacteria has become one of the biggest health concerns globally, and an enormous effort has been made to combat them. However, despite the efforts, the emergence of resistant strains is rapidly increasing, while the discovery of new classes of antibiotics has lagged. For this reason, it is pivotal to acquire a more detailed knowledge of bacterial resistance mechanisms and the mechanism of action of substances with antibacterial effects to identify biomarkers, therapeutic targets, and the development of new antibiotics. Metabolomics and proteomics, combined with mass spectrometry for data acquisition, are suitable techniques and have already been applied successfully. This review presents basic aspects of the metabolomic and proteomic approaches and their application for the elucidation of bacterial resistance mechanisms.
Subject(s)
Anti-Bacterial Agents , Bacteria , Drug Resistance, Bacterial , Mass Spectrometry , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria/drug effects , Bacteria/genetics , Bacterial Infections/microbiology , Metabolomics , Proteomics , Drug Resistance, Bacterial/geneticsABSTRACT
Zoanthids of the genus Palythoa are distributed worldwide in shallow waters around coral reefs. Like all cnidarians, they possess nematocysts that contain a large diversity of toxins that paralyze their prey. This work was aimed at isolating and functionally characterizing a cnidarian neurotoxic phospholipase named A2-PLTX-Pcb1a for the first time. This phospholipase was isolated from the venomous extract of the zoanthid Palythoa caribaeorum. This enzyme, which is Ca2+-dependent, is a 149 amino acid residue protein. The analysis of the A2-PLTX-Pcb1a sequence showed neurotoxic domain similitude with other neurotoxic sPLA2´s, but a different catalytic histidine domain. This is remarkable, since A2-PLTX-Pcb1a displays properties like those of other known PLA2 enzymes.
Subject(s)
Anthozoa , Motor Cortex/drug effects , Neurotoxicity Syndromes , Neurotoxins/toxicity , Phospholipases A2/toxicity , Animals , Behavior, Animal/drug effects , Injections, Intraventricular , Male , Motor Activity/drug effects , Motor Cortex/pathology , Neurotoxins/chemistry , Neurotoxins/isolation & purification , Phospholipases A2/chemistry , Phospholipases A2/isolation & purification , Rats, WistarABSTRACT
Natural products from animal venoms have been used widely in the discovery of novel molecules with particular biological activities that enable their use as potential drug candidates. The phylum Cnidaria (jellyfish, sea anemones, corals zoanthids, hydrozoans, etc.) is the most ancient venomous phylum on earth. Its venoms are composed of a complex mixture of peptidic compounds with neurotoxic and cytolitic properties that have shown activity on mammalian systems despite the fact that they are naturally targeted against fish and invertebrate preys, mainly crustaceans. For this reason, cnidarian venoms are an interesting and vast source of molecules with a remarkable activity on central nervous system, targeting mainly voltage-gated ion channels, ASIC channels, and TRPV1 receptors. In this brief review, we list the amino acid sequences of most cnidarian neurotoxic peptides reported to date. Additionally, we propose the inclusion of a new type of voltage-gated sea anemone sodium channel toxins based on the most recent reports.
