Cyclic peptides are receiving significant attention thanks to their antimicrobial activity and high serum stability, which is useful to develop and design novel antimicrobial agents. Antimicrobial peptides appear to be key components of innate defences against bacteria, viruses, and fungi. Among the others, defensins possess a strong microbicidial activity. Defensins are cationic and amphipathic peptides with six cysteine residues connected by three disulfide bonds found in plants, insects, and mammals; they are divided in three families: α-, β-, and θ-defensins. α-Defensins are contained in the primary granules of human neutrophils; β-defensins are expressed in human epithelia; and θ-defensins are pseudo-cyclic defensins not found in humans, but in rhesus macaques. The structural diversities among the three families are reflected in a different antimicrobial action as well as in serum stability. The engineering of these peptides is an exciting opportunity to obtain more functional antimicrobial molecules highlighting their potential as therapeutic agents. The present review reports the most recent advances in the field of cyclic peptides with a specific regard to defensin analogs.
Glucose dehydrogenase has been purified to homogeneity from cell extracts of the extreme thermoacidophilic archaebacterium Sulfolobus solfataricus. The enzyme utilizes both NAD+ and NADP+ as coenzyme and catalyses the oxidation of several monosaccharides to the corresponding glyconic acid. Substrate specificity and oxidation rate depend on the coenzyme present; when NAD+ is used, the enzyme binds and oxidizes specifically sugars presenting equatorial orientation of hydroxy groups at C-2, C-3 and C-4. The Mr of the native enzyme is 124,000 and decreases to about 60,000 in the presence of 6 M-guanidinium chloride and to about 30,000 in the presence of 5% (w/v) SDS. The enzyme shows maximal activity at pH 9, 77 degrees C and 20 mM-Mg2+, -Mn2+ or -Ca2+ and is fairly stable in the presence of chaotropic agents and water-miscible organic solvents such as methanol or acetone.
Staphylococcus aureus is a microorganism capable of causing numerous diseases of the human skin. The incidence of S. aureus skin infections reflects the conflict between the host skin′s immune defenses and the S. aureus’ virulence elements. Antimicrobial peptides (AMPs) are small protein molecules involved in numerous biological activities, playing a very important role in the innate immunity. They constitute the defense of the host′s skin, which prevents harmful microorganisms from entering the epithelial barrier, including S. aureus. However, S. aureus uses ambiguous mechanisms against host defenses by promoting colonization and skin infections. Our review aims to provide a reference collection on host-pathogen interactions in skin disorders, including S. aureus infections and its resistance to methicillin (MRSA). In addition to these, we discuss the involvement of defensins and other innate immunity mediators (i.e., toll receptors, interleukin-1, and interleukin-17), involved in the defense of the host against the skin disorders caused by S. aureus, and then focus on the evasion mechanisms developed by the pathogenic microorganism under analysis. This review provides the “state of the art” on molecular mechanisms underlying S. aureus skin infection and the pharmacological potential of AMPs as a new therapeutic strategy, in order to define alternative directions in the fight against cutaneous disease.
The effect of <5 KDa (low molecular weight, LMW) and >5 KDa (high molecular weight, HMW) humic fractions on transport activities of isolated plasma membrane vesicles was studied. The K ÷-stimulated component of the ATP-hydrolyzing activity was considerably increased by LMW humic substances at concentrations ranging from 0.075 mg org C L 1 to 1 mg org C L -1. The stimulation was still evident when the detergent Brij-35 was added in the assay mixture, indicating a direct effect of LMW humic substances on plasma membrane ATPase activity. The LMW humic fraction stimulated ATP-dependent intravesicular H+-accumulation with a pattern similar to that recorded for ATP hydrolysis. LMW humic substances induced also an increase in passive membrane permeability to protons, as revealed by following the dissipation of an artificially imposed pH gradient. Membrane permeability to anions, as measured by the anion-dependent active proton accumulation was affected by LMW humic substances. In the presence of NO 3 these molecules clearly enhanced proton transport, while C1--dependent activity was almost unaffected, thus suggesting a specific action of LMW humic fraction on transmembrane NO 3 fluxes. On the other hand, HMW humic substances decreased the passive permeability to protons and reduced the anion-dependent intravesicular H+-accumulation. The results suggest that the stimulatory effect of soil humic substances on plant nutrition and growth might be, at least in part, explained on the basis of both direct action of LMW humic molecules on plasma membrane H+-ATPase and specific modification of cell membrane permeability.
The gut microbiota is significantly involved in the preservation of the immune system of the host, protecting it against the pathogenic bacteria of the stomach. The correlation between gut microbiota and the host response supports human gastric homeostasis. Gut microbes may be shifted in Helicobacter pylori (Hp)-infected individuals to advance gastric inflammation and distinguished diseases. Particularly interesting is the establishment of cooperation between gut microbiota and antimicrobial peptides (AMPs) of the host in the gastrointestinal tract. AMPs have great importance in the innate immune reactions to Hp and participate in conservative co-evolution with an intricate microbiome. β-Defensins, a class of short, cationic, arginine-rich proteins belonging to the AMP group, are produced by epithelial and immunological cells. Their expression is enhanced during Hp infection. In this review, we discuss the impact of the gut microbiome on the host response, with particular regard to β-defensins in Hp-associated infections. In microbial infections, mostly in precancerous lesions induced by Hp infection, these modifications could lead to different outcomes.
Acute or strenuous exercise is sometimes related to upper respiratory tract infections in athletes. Practicing intense and regular exercise can lead to incorrect activation of the immune system, causing athletes to be excluded from training programs and competitions. Defensins are small antimicrobial peptides that are part of the innate immune system and dynamically involved in several biological activities. In this study, we highlight the role of human defensins in competitive basketball athletes. In particular, we consider the behavior of alpha- and beta-defensins together with white blood cells in a cohort of players. Moreover, we focus our attention on cortisol, a physiological indicator of stress, and testosterone, both of which are human hormones involved in muscle metabolism. The free-testosterone/cortisol ratio is considered to be an indicator of overtraining among athletes. This paper provides an up-to-date information of the role of human defensins as self-defense molecules during a continuous stressor such as long-term exercise, and it recognizes them as potential markers of infection.
Peroxidase isozymes from winter wheat (Triticum aestivum L. cv Orso) seedlings extracts showed phenoloxidase-like activity, becoming visible on polyacrylamide gels also in the absence of hydrogen peroxide. The results obtained after a characterization of the two activities, based on their substrate specificity, on their selective inhibition, and on the possible occurrence of artifacts, suggested the existence of polyfunctional peroxidase isozymes. Different isozymes possessing only phenol oxidase activity were not found in the same plant material. This appears to be the first evidence of phenoloxidase-acting isoperoxidases in winter wheat.
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