Clavanin A improves outcome of complications from different bacterial infections.

The rapid increase in the incidence of multidrug-resistant infections today has led to enormous interest in antimicrobial peptides (AMPs) as suitable compounds for developing unusual antibiotics. In this study, clavanin A, an antimicrobial peptide previously isolated from the marine tunicate Styela clava, was selected as a purposeful molecule that could be used in controlling infection and further synthesized. Clavanin A was in vitro evaluated against Staphylococcus aureus and Escherichia coli as well as toward L929 mouse fibroblasts and skin primary cells (SPCs). Moreover, this peptide was challenged here in an in vivo wound and sepsis model, and the immune response was also analyzed. Despite displaying clear in vitro antimicrobial activity toward Gram-positive and -negative bacteria, clavanin A showed no cytotoxic activities against mammalian cells, and in acute toxicity tests, no adverse reaction was observed at any of the concentrations. Moreover, clavanin A significantly reduced the S. aureus CFU in an experimental wound model. This peptide also reduced the mortality of mice infected with E. coli and S. aureus by 80% compared with that of control animals (treated with phosphate-buffered saline [PBS]): these data suggest that clavanin A prevents the start of sepsis and thereby reduces mortality. These data suggest that clavanin A is an AMP that could improve the development of novel peptide-based strategies for the treatment of wound and sepsis infections.

Cn-AMP1: a new promiscuous peptide with potential for microbial infections treatment.

The antimicrobial peptides (AMPs) are evolutionarily ancient molecules that act as components of the innate immune system. Recently, it was demonstrated that a single AMP can perform various functions; this ability is known as "peptide promiscuity." However, little is known about promiscuity in plant AMPs without disulfide bonds. This study was carried out to evaluate the promiscuity of Cn-AMP1: a promising disulfide-free plant peptide with reduced size and cationic and hydrophobic properties. Its activity against human pathogenic bacteria and fungal pathogens, as well as its in vitro immunostimulatory activity and effects on cancerous and healthy mammalian cell proliferation were studied here. Cn-AMP1 exerts antimicrobial effects against Gram-positive bacteria, Gram-negative bacteria, and fungi. Moreover, tumor cell viability activity in Caco-2 cells, as well as immunostimulatory activity by evaluating upregulated inflammatory-cytokine secretion by monocytes was also positively observed. Cn-AMP1 does not exhibit a well-defined conformation in aqueous solution and probably undergoes a 3(10)-helix transition in hydrophobic environments. The experimental results support the promiscuous activity of Cn-AMP1, presenting a wide range of activities, including antibacterial, antifungal, and immunostimulatory activity. In the future, Cn-AMP1 should be used in the development of novel biopharmaceuticals, mainly due to its reduced size and broad spectrum of activity.

Evaluation of an antimicrobial L-amino acid oxidase and peptide derivatives from Bothropoides mattogrosensis pitviper venom.

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.