The peptide clavanin A significantly increases survival. model. This peptide also reduced the mortality of mice infected withE. coliandS. aureusby 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. == INTRO == Throughout life, the human body continuously interacts with different types of microorganisms, including commensal bacteria that colonize skin and mucous membranes (1). In most cases, invading pathogens can be effectively eradicated by our immune system. Nowadays, infectious diseases remain a major health problem, accounting for around 18% of deaths worldwide (1). The skin has got the largest surface area of all the body organs and is the most exposed of them. Although the skin provides effective protection from the external environment, skin infections can occur by bacteria, fungi, or viruses. These infections are often the result of a breach of skin integrity, accompanied by the access of pathogens into the dermis (2). Skin infections are quite common, but when treated quickly are not usually dangerous. However , in cases where the patient remains with an untreated contamination, it can evolve to a more serious condition, which could lead to sepsis and death (3, 4). The most frequent bacterial sepsis-associated species areStaphylococcus aureus(30%, including 14% methicillin resistant), Pseudomonasspp. (14%), andEscherichia coli(13%) (5). Sepsis is a complex and dynamic disease characterized by an exacerbated and systemic immune Afzelin response to invading pathogens or their related toxins (6, 7). This immune response includes pathogen recognition, which triggers the release of inflammatory mediators, such as peptides and proteins, as well as systemic activation of the enhance and coagulation cascade (6). Despite improvements in health care procedures, the incidence of sepsis has increased in recent years, increasing mortality and the period of hospitalization (3, 6). Currently, several alternative methods are used for the treatment of local Rabbit polyclonal to CIDEB and systemic bacterial infections, producing effective results in clinical trials (8, 9). Therefore , the investigation of new and uncommon therapies is vitally important. In this context, antimicrobial peptides (AMPs) appear to be superb candidates. AMPs are major short cationic and amphipathic molecules ( <60 protein residues) with heterogeneous and multiple action modes that may directly lead to bacterial death, besides having immunomodulatory activity (10, 11). The search for novel antibiotics has become more intense in recent decades, in response to progressively frequent reports of multiresistant pathogens or the side effects caused Afzelin by antibiotics on the market today (10). Clavanin A includes an AMP isolated from the hemocytes from the marine tunicateStyela clava(12). In addition to cationic amphipathic characteristics, this peptide also reveals a sequence rich in histidine, phenylalanine, and glycine residues (13). Clavanin A is broadly effective against Gram-positive bacteria, including methicillin-resistantStaphylococcus aureusand Gram-negative bacteria and fungi (12, 14). These peptides are active in high-salt concentrations and in acidic pH. Nevertheless little is known about the proteolytic and thermal stability of clavanin forms (12, 14). Due to these unique characteristics, clavanin A was investigated in this study with regard to its biological properties, such as its Afzelin antibacterial activity (in vitroandin vivo) and toxicity. == COMPONENTS AND METHODS == == Peptide synthesis. == Almost all peptides used here (clavanin A and the cathelicidin LL-37) were synthesized by Shanghai Hanhong Chemical (China) using the solid phase with theN-9-fluorenylmethyloxycarbonyl (Fmoc) strategy and purified by high-performance liquid chromatography (HPLC) (12, 15). The purity from the peptide utilized in biologic assays.