title: Evaluation of an antimicrobial L-amino acid oxidase and peptide derivatives from Bothropoides mattogrosensis pitviper venom.
abstract: Healthcare-associated infections (HAIs) are causes of mortality and morbidity worldwide. The prevalence of bacterial resistance to common antibiotics has increased in recent years, highlighting the need to develop novel alternatives for controlling these pathogens. Pitviper venoms are composed of a multifaceted mixture of peptides, proteins and inorganic components. L-amino oxidase (LAO) is a multifunctional enzyme that is able to develop different activities including antibacterial activity. In this study a novel LAO from Bothrops mattogrosensis (BmLAO) was isolated and biochemically characterized. Partial enzyme sequence showed full identity to Bothrops pauloensis LAO. Moreover, LAO here isolated showed remarkable antibacterial activity against Gram-positive and -negative bacteria, clearly suggesting a secondary protective function. Otherwise, no cytotoxic activities against macrophages and erythrocytes were observed. Finally, some LAO fragments (BmLAO-f1, BmLAO-f2 and BmLAO-f3) were synthesized and further evaluated, also showing enhanced antimicrobial activity. Peptide fragments, which are the key residues involved in antimicrobial activity, were also structurally studied by using theoretical models. The fragments reported here may be promising candidates in the rational design of new antibiotics that could be used to control resistant microorganisms.
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, Mato Grosso do Sul, Brazil.
authors.forename: Brunna M
authors.initials: BM
authors.lastname: Okubo
authors.forename: Osmar N
authors.initials: ON
authors.lastname: Silva
authors.forename: Ludovico
authors.initials: L
authors.lastname: Migliolo
authors.forename: Diego G
authors.initials: DG
authors.lastname: Gomes
authors.forename: William F
authors.initials: WF
authors.lastname: Porto
authors.forename: Carla L
authors.initials: CL
authors.lastname: Batista
authors.forename: Carmel S
authors.initials: CS
authors.lastname: Ramos
authors.forename: Hortência H S
authors.initials: HH
authors.lastname: Holanda
authors.forename: Simoni C
authors.initials: SC
authors.lastname: Dias
authors.forename: Octavio L
authors.initials: OL
authors.lastname: Franco
authors.forename: Susana E
authors.initials: SE
authors.lastname: Moreno
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D050830:L-Amino Acid Oxidase / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D017819:Viperidae / Q000235:genetics
chemical_list: D023181:Antimicrobial Cationic Peptides; D003435:Crotalid Venoms; D010446:Peptide Fragments; D050830:L-Amino Acid Oxidase