Evolving and assembling to pierce through: Evolutionary and structural aspects of antimicrobial peptides.

The burgeoning menace of antimicrobial resistance across the globe has necessitated investigations into other chemotherapeutic strategies to combat infections. Antimicrobial peptides, or host defense peptides, are a set of promising therapeutic candidates in this regard. Most of them cause membrane permeabilization and are a key component of the innate immune response to pathogenic invasion. It has also been reported that peptide self-assembly is a driving factor governing the microbicidal activity of these peptide candidates. While efforts have been made to develop novel synthetic peptides against various microbes, many clinical trials of such peptides have failed due to toxicity and hemolytic activity to the host. A function-guided rational peptide engineering, based on evolutionary principles, physicochemical properties and activity determinants of AMP activity, is expected to help in targeting specific microbes. Furthermore, it is important to develop a unified understanding of the evolution of AMPs in order to fully appreciate their importance in host defense. This review seeks to explore the evolution of AMPs and the physicochemical determinants of AMP activity. The specific interactions driving AMP self-assembly have also been reviewed, emphasizing implications of this self-assembly on microbicidal and immunomodulatory activity.

Natural products and their semi-synthetic derivatives against antimicrobial-resistant human pathogenic bacteria and fungi.

Human infectious diseases caused by various microbial pathogens, in general, impact a large population of individuals every year. These microbial diseases that spread quickly remain to be a big issue in various health-related domains and to withstand the negative drug impacts, the antimicrobial-resistant pathogenic microbial organisms (pathogenic bacteria and pathogenic fungi) have developed a variety of resistance processes against many antimicrobial drug classes. During the COVID-19 outbreak, there seems to be an upsurge in drug and multidrug resistant-associated pathogenic microbial species. The preponderance of existing antimicrobials isn't completely effective, which limits their application in clinical settings. Several naturally occurring chemicals produced from bacteria, plants, animals, marine species, and other sources are now being studied for antimicrobial characteristics. These natural antimicrobial compounds extracted from different sources have been demonstrated to be effective against a variety of diseases, although plants remain the most abundant source. These compounds have shown promise in reducing the microbial diseases linked to the development of drug tolerance and resistance. This paper offers a detailed review of some of the most vital and promising natural compounds and their derivatives against various human infectious microbial organisms. The inhibitory action of different natural antimicrobial compounds, and their possible mechanism of antimicrobial action against a range of pathogenic fungal and bacterial organisms, is provided. The review will be useful in refining current antimicrobial (antifungal and antibacterial) medicines as well as establishing new treatment strategies to tackle the rising number of human bacterial and fungal-associated infections.

Gut microbial metabolome in inflammatory bowel disease: From association to therapeutic perspectives.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a set of clinically chronic, relapsing gastrointestinal inflammatory disease and lacks of an absolute cure. Although the precise etiology is unknown, developments in high-throughput microbial genomic sequencing significantly illuminate the changes in the intestinal microbial structure and functions in patients with IBD. The application of microbial metabolomics suggests that the microbiota can influence IBD pathogenesis by producing metabolites, which are implicated as crucial mediators of host-microbial crosstalk. This review aims to elaborate the current knowledge of perturbations of the microbiome-metabolome interface in IBD with description of altered composition and metabolite profiles of gut microbiota. We emphasized and elaborated recent findings of several potentially protective metabolite classes in IBD, including fatty acids, amino acids and derivatives and bile acids. This article will facilitate a deeper understanding of the new therapeutic approach for IBD by applying metabolome-based adjunctive treatment.

Localization of antimicrobial peptides in the tunic of Ciona intestinalis (Ascidiacea, Tunicata) and their involvement in local inflammatory-like reactions.

Tunicates comprising a wide variety of different species synthesize antimicrobial peptides as important effector molecules of the innate immune system. Recently, two putative gene families coding for antimicrobial peptides were identified in the expressed sequence tag database of the tunicate Ciona intestinalis. Two synthetic peptides representing the cationic core region of one member of each of the families displayed potent antibacterial and antifungal activities. Moreover, the natural peptides were demonstrated to be synthesized and stored in distinct hemocyte types. Here, we investigated the presence of these natural peptides, namely Ci-MAM-A and Ci-PAP-A, in the tunic of C. intestinalis considering that the ascidian tunic is a body surface barrier exposed to constant microbial assault. Furthermore, as the tunic may represent a major route of entry for pathogen invasion after its damage we monitored the location of these peptides upon a local inflammatory-like reaction induced by injection of foreign cells. Using immunocytochemistry and electron microscopy both peptides were localized to the tunic and were massively present in granulocytes of inflamed tissue. Conclusively, antimicrobial peptides may constitute a chemical barrier within the tunic of urochordates.