N-glycan breakdown by bacterial CAZymes.

The modification of proteins by N-glycans is ubiquitous to most organisms and they have multiple biological functions, including protecting the adjoining protein from degradation and facilitating communication or adhesion between cells, for example. Microbes have evolved CAZymes to deconstruct different types of N-glycans and some of these have been characterised from microbes originating from different niches, both commensals and pathogens. The specificity of these CAZymes provides clues as to how different microbes breakdown these substrates and possibly cross-feed them. Discovery of CAZymes highly specific for N-glycans also provides new tools and options for modifying glycoproteins.

Computational tools for exploring peptide-membrane interactions in gram-positive bacteria.

The vital cellular functions in Gram-positive bacteria are controlled by signaling molecules known as quorum sensing peptides (QSPs), considered promising therapeutic interventions for bacterial infections. In the bacterial system QSPs bind to membrane-coupled receptors, which then auto-phosphorylate and activate intracellular response regulators. These response regulators induce target gene expression in bacteria. One of the most reliable trends in drug discovery research for virulence-associated molecular targets is the use of peptide drugs or new functionalities. In this perspective, computational methods act as auxiliary aids for biologists, where methodologies based on machine learning and in silico analysis are developed as suitable tools for target peptide identification. Therefore, the development of quick and reliable computational resources to identify or predict these QSPs along with their receptors and inhibitors is receiving considerable attention. The databases such as Quorumpeps and Quorum Sensing of Human Gut Microbes (QSHGM) provide a detailed overview of the structures and functions of QSPs. The tools and algorithms such as QSPpred, QSPred-FL, iQSP, EnsembleQS and PEPred-Suite have been used for the generic prediction of QSPs and feature representation. The availability of compiled key resources for utilizing peptide features based on amino acid composition, positional preferences, and motifs as well as structural and physicochemical properties, including biofilm inhibitory peptides, can aid in elucidating the QSP and membrane receptor interactions in infectious Gram-positive pathogens. Herein, we present a comprehensive survey of diverse computational approaches that are suitable for detecting QSPs and QS interference molecules. This review highlights the utility of these methods for developing potential biomarkers against infectious Gram-positive pathogens.

Structure and evolution of the bifidobacterial carbohydrate metabolism proteins and enzymes.

Bifidobacteria have attracted significant attention because they provide health-promoting effects in the human gut. In this review, we present a current overview of the three-dimensional structures of bifidobacterial proteins involved in carbohydrate uptake, degradation, and metabolism. As predominant early colonizers of the infant's gut, distinct bifidobacterial species are equipped with a panel of transporters and enzymes specific for human milk oligosaccharides (HMOs). Interestingly, Bifidobacterium bifidum and Bifidobacterium longum possess lacto-N-biosidases with unrelated structural folds to release the disaccharide lacto-N-biose from HMOs, suggesting the convergent evolution of this activity from different ancestral proteins. The crystal structures of enzymes that confer the degradation of glycans from the mucin glycoprotein layer provide a structural basis for the utilization of this sustainable nutrient in the gastrointestinal tract. The utilization of several plant dietary oligosaccharides has been studied in detail, and the prime importance of oligosaccharide-specific ATP-binding cassette (ABC) transporters in glycan utilisations by bifidobacteria has been revealed. The structural elements underpinning the high selectivity and roles of ABC transporter binding proteins in establishing competitive growth on preferred oligosaccharides are discussed. Distinct ABC transporters are conserved across several bifidobacterial species, e.g. those targeting arabinoxylooligosaccharide and α-1,6-galactosides/glucosides. Less prevalent transporters, e.g. targeting ß-mannooligosaccharides, may contribute to the metabolic specialisation within Bifidobacterium. Some bifidobacterial species have established symbiotic relationships with humans. Structural studies of carbohydrate-utilizing systems in Bifidobacterium have revealed the interesting history of molecular coevolution with the host, as highlighted by the early selection of bifidobacteria by mucin and breast milk glycans.

Catabolic Machinery of the Human Gut Microbes Bestow Resilience Against Vanillin Antimicrobial Nature.

Vanillin is a phenolic food additive commonly used for flavor, antimicrobial, and antioxidant properties. Though it is one of the widely used food additives, strategies of the human gut microbes to evade its antimicrobial activity await extensive elucidation. The current study explores the human gut microbiome with a multi-omics approach to elucidate its composition and metabolic machinery to counter vanillin bioactivity. A combination of SSU rRNA gene diversity, metagenomic RNA features diversity, phylogenetic affiliation of metagenome encoded proteins, uniformly (R = 0.99) indicates the abundance of Bacteroidetes followed by Firmicutes and Proteobacteria. Manual curation of metagenomic dataset identified gene clusters specific for the vanillin metabolism (ligV, ligK, and vanK) and intermediary metabolic pathways (pca and cat operon). Metagenomic dataset comparison identified the omnipresence of vanillin catabolic features across diverse populations. The metabolomic analysis brings forth the functionality of the vanillin catabolic pathway through the Protocatechuate branch of the beta-ketoadipate pathway. These results highlight the human gut microbial features and metabolic bioprocess involved in vanillin catabolism to overcome its antimicrobial activity. The current study advances our understanding of the human gut microbiome adaption toward changing dietary habits.

[Research and prospect of Traditional Chinese Medical Microecology].

In the long-term evolution, microbes and hosts coexist widely, forming a symbiotic microecosystem and resulting the complex interactions of the metabolism. With the application of microecological theory in Chinese materia medica science, two main points have been accepted gradually. On the one hand, the prevention and treatment of human diseases by traditional Chinese medicines can be achieved through the correction and adjustment of the imbalance of the human microecosystem. On the other hand, the microecosystem can regulate the quality of traditional Chinese medicines in real time, and further affect their curative effect. Thus, a new discipline, Traditional Chinese Medical Microecology, has been gradually established. In this review, the background, theoretical structure, research directions, key problems and the relationship with human microecology of Traditional Chinese Medical Microecology were systematically summarized and prospected for promoting its development. Moreover, this review provides a reference protocol for further discoursing the microecological mechanism involving the efficacy of traditional Chinese medicines.

S9A Serine Protease Engender Antigenic Gluten Catabolic Competence to the Human Gut Microbe.

The human gut microbiome has a significant role in host physiology; however its role in gluten catabolism is debatable. Present study explores the role of human gut microbes in gluten catabolism and a native human gut microbe Cellulomonas sp. HM71 was identified. SSU rDNA analysis has described human gut microbiome structure and also confirmed the permanent residentship of Cellulomonas sp. HM71. Catabolic potential of Cellulomonas sp. HM71 to cleave antigenic gluten peptides indicates presence of candidate gene encoding biocatalytic machinery. Genome analysis has identified the presence of gene encoding S9A serine protease family-prolyl endopeptidase, with Ser591, Asp664 and His685 signature residues. Cellulomonas sp. HM71 prolyl endopeptidase activity was found optimal at pH 7.0 and 37 °C with a KM of 35.53 µmol and specifically cleaves at proline residue. Current study describes the gluten catabolism potential of Cellulomonas sp. HM71 depicting possible role of human gut microbes in gluten catabolism to confer resistance mechanisms for the onset of celiac diseases in populations with gluten diet.

Research and prospect of Traditional Chinese Medical Microecology / 中国中药杂志

In the long-term evolution, microbes and hosts coexist widely, forming a symbiotic microecosystem and resulting the complex interactions of the metabolism. With the application of microecological theory in Chinese materia medica science, two main points have been accepted gradually. On the one hand, the prevention and treatment of human diseases by traditional Chinese medicines can be achieved through the correction and adjustment of the imbalance of the human microecosystem. On the other hand, the microecosystem can regulate the quality of traditional Chinese medicines in real time, and further affect their curative effect. Thus, a new discipline, Traditional Chinese Medical Microecology, has been gradually established. In this review, the background, theoretical structure, research directions, key problems and the relationship with human microecology of Traditional Chinese Medical Microecology were systematically summarized and prospected for promoting its development. Moreover, this review provides a reference protocol for further discoursing the microecological mechanism involving the efficacy of traditional Chinese medicines.