Biology subjects

Mondal, S. I.

Publications and source records attributed to Mondal, S. I..

6 recordsLinked to original sources

bioRxiv2026

Human Gut Phageome Analysis Uncovers Thousands of Highly Modular Endolysins

The escalating threat of antimicrobial resistance has renewed global interest in bacteriophages as precise and powerful tools for controlling bacterial populations in the human gut. These viruses owe much of their antibacterial potential to phage-encoded endolysins, enzymes capable of rapidly degrading bacterial cell walls with high specificity and low potential for resistance development. Despite their therapeutic promise, the overall composition of the gut phageome and the structural modularity of its endolysins remain poorly understood. In this study, we performed a large-scale analysis of 9,141 human gut metagenomic samples from 34 independent studies. Using standardized workflows for assembly, genome clustering, host prediction, and protein domain annotation, we reconstructed 15,267 phage genomes and identified 3,794 corresponding endolysins. The recovered genomes showed substantial variation in size and coding density, with an average GC content of 43%. Host prediction indicated that most phages targeted bacterial members of the phyla Bacillota (41%) and Bacteroidota (23%). Endolysin sequences grouped into 296 protein families and displayed striking domain modularity. Catalytic domains such as Amidase_2 and Glyco_hydro_25 frequently co-occurred with cell wall-binding motifs including LysM and CW_7. Remarkably, one endolysin contained 15 distinct domains, the highest natural domain diversity reported to date. Collectively, this study represents the most comprehensive characterization of the human gut phageome and its encoded endolysins to date. The exceptional modular diversity uncovered highlights the gut phageome as a rich reservoir of endolysin variants, providing a strong foundation for developing next-generation therapeutics against multidrug-resistant bacterial pathogens.

genomics↗

bioRxiv2025

Genomic Insights into Wolbachia Strain wCin2USA1 Reveal Promising Cytoplasmic Incompatibility Potential and Next-Generation Dengue Biocontrol

Dengue fever poses a growing public health challenge globally, resulting in significant morbidity and economic burden. The use of Wolbachia-mediated biocontrol represents a promising, cost-effective, and environmentally sustainable strategy for managing dengue transmission. However, the susceptibility of existing Wolbachia strains utilized in controlling Aedes aegypti necessitates the investigation of novel strains to enhance dengue control efficacy. This study aimed to identify potential alternative Wolbachia strains for dengue control by comparing the genomes of seven Wolbachia pipientis strains: wMel, wAlbB, wlrr, wHm-C, wAnm, ant7, and a strain isolated from Aedes aegypti. We conducted comprehensive genomic analyses, including phylogenetic assessments, metabolic pathway evaluations, and characterization of the Cytoplasmic Incompatibility Factor (Cif) genes. Our analyses identified the strain wCin2USA1 as a strong candidate for alternative dengue control strategies. This strain demonstrated remarkable genomic similarities to wMel, an already established strain used as biocontrol for Aedes aegypti. Importantly, this strain presented two distinct pairs of Cif genes from different monophyletic types, each homologous to the Cif genes found in wMel and wAlbB. This genetic architecture suggests a high degree of compatibility and demonstrates promising potential for the suppression of Aedes aegypti populations through the induction of Cytoplasmic Incompatibility. The presence of multiple intact prophage regions also suggests greater adaptability compared to established strains. Our findings support the hypothesis that wCin2USA1 could serve as an effective biocontrol agent against dengue transmission. This work provides critical insights into developing innovative Wolbachia-based interventions aimed at mitigating the persistent threat posed by dengue fever. Future research should concentrate on optimizing release methodologies, evaluating ecological impacts, and assessing the strains effectiveness against the dengue virus. Author SummaryDengue fever is one of the fastest-growing mosquito-borne diseases in the world, causing illness and economic challenges in many countries. Current mosquito control methods, such as insecticides, are often costly, less effective over time, and harmful to the environment. An alternative approach uses naturally occurring bacteria called Wolbachia, which live inside insects. When certain Wolbachia strains are introduced into mosquitoes, they can reduce the insects ability to spread viruses like dengue. In our study, we compared the genetic makeup of several Wolbachia strains to identify new candidates that may work better for controlling dengue. We discovered that a strain called wCin2USA1 has strong potential because it shares important features with two strains already used successfully, while also having unique advantages. These include genes that help prevent mosquitoes from reproducing normally when carrying different Wolbachia strains, which can reduce mosquito populations. Our findings suggest that wCin2USA1 could be developed as a new, environmentally friendly tool to help reduce dengue transmission.

genomics↗

bioRxiv2024

Streptococcus Phage Genomes Reveal Extensive Diversity, New Taxonomic Insights, and Novel Endolysin-Derived Antimicrobial Peptides

The global rise of antibiotic-resistant bacteria, particularly among Streptococcus species, poses an escalating public health threat. Traditional antibiotic development has proven inadequate, making innovative approaches such as bacteriophage-based therapies promising alternatives. A deep understanding of phage biology at the genomic level is essential for advancing therapeutic applications. Here, we analyzed 709 Streptococcus phage genomes to bridge gaps in genomic diversity and propose revisions to Streptococcus phage taxonomy. The phage genomes were clustered based on shared proteins, resulting in 66 clusters and 35 singletons with significant variation in genome characteristics. Through proteome phylogeny, average nucleotide identity, and inter-cluster core genes, we propose 21 new family-level classifications and 296 genus-level subclusters, providing an updated framework for Streptococcus phage taxonomy. Further analysis revealed diverse domain architectures in Streptococcus phage endolysins, including previously unreported structures. Specific domains were associated with distinct streptococcal hosts, suggesting adaptive evolution. We also observed variation in endolysin gene organization, with purifying selection acting on most sites, though some were subject to diversifying selection. Additionally, 182 novel endolysin-derived antimicrobial peptides (AMPs) were identified, some exhibiting antifungal, antiviral, cell-penetrating and non-toxic properties. Molecular dynamics and docking simulations demonstrated high stability and strong binding affinity of peptides EP-39 and EP-121 to the Streptococcus pneumoniae virulence factor autolysin. This is the first comprehensive comparative study of Streptococcus phage genomes, providing critical insights into phage diversity and taxonomy. It also highlights the therapeutic potential of endolysin-derived AMPs against multidrug-resistant Streptococcus strains. Further experimental validation is required to assess their clinical potential.

genomics↗

bioRxiv2024

Comparative genomics reveals diversity and taxonomic relationships among Clostridioides difficile phages

Clostridioides difficile is associated with life-threatening antibiotic-associated diarrhea, colitis, and toxin-mediated infections. While antibiotics are the primary treatment against C. difficile infections, increasing resistance necessitates alternatives. Bacteriophages and bacteriophage-derived proteins such as endolysins hold promise as potential solutions. Understanding phage biology at the genomic level is crucial for their therapeutic use. We conducted a comparative genomic analysis of 44 C. difficile phage genomes from public databases, examining both whole genome and proteome levels and grouping them by shared protein content. Relationships within each group were observed, and core and highly conserved genes were identified. Using genome and proteome phylogeny, average nucleotide identity, and core gene identification, we proposed an updated taxonomic classification. Nine distinct clusters were identified, without any singleton. Cluster members exhibited similar genome architecture, genome sizes, GC content, number of coding sequences, presence of core genes, and high nucleotide identity. Additionally, we propose 23 new genera, three families and the elevation of currently assigned genera to subfamilies. The lytic module proteins, endolysins, and holins were also characterized, revealing four distinct endolysin organizations with diverse domain architectures. Notably, the amidase_3 and LysM domains were highly conserved and subjected to purifying selection within the C. difficile phage genomes. This is the first comprehensive comparative study regarding C. difficile phage genomes. Our study provides valuable genomic insights that add to the current understanding of the phages. Our taxonomic analysis may improve the classification scheme of C. difficile phages and aid in the future classification of newly isolated C. difficile phage genomes.

genomics↗

bioRxiv2023

Multiphoton imaging of glucose, galactose, and fructose-induced formation of fluorescent advanced glycation end products in tissues

Blood glucose and HbA1c, intermediate glycation products of hemoglobin, remain the two clinical biomarkers for monitoring disease progression in diabetics. However, the formation of advanced glycation end products (AGEs) has been implicated in diabetic pathogenesis and the use of AGEs in tissues as long-term glycemic markers may be of value in the clinical setting. Therefore, it is necessary to understand how different tissue constituents respond to dietary monosaccharides. In this study, we studied the in vitro rate of fluorescent AGEs (fAGEs) formation with multiphoton microscopy in different porcine tissues (aorta, cornea, kidney, dermis, and tendon). These tissues were treated with D-glucose, D-galactose, and D-fructose, three primary monosaccharides found in human diets. We found that the use of D-fructose resulted in the highest glycation rate, followed by D-galactose and then D-glucose. Moreover, compared to non-collagen tissue constituents such as elastic fibers and cells, the rate of tissue glycation was consistently higher in collagen, suggesting that collagen is a more sensitive target for fAGE formation. However, we also found that collagen in different tissues exhibits different rates of fAGE formation, with slower rates observed in tightly packed tissues such as cornea and tendon. Our study suggests that for fAGE to be developed into a long-term glycemic biomarker, loosely organized collagen tissues located in the proximity of vasculature may be the best targets.

biophysics↗

bioRxiv2020

Proteome Exploration of Legionella pneumophila for Identifying Novel Therapuetics: A Hierarchical Subtractive Genomics and Reverse Vaccinology Approach

Legionella pneumophila, the causative agent of a serious type of pneumonia (lung infection) called Legionnaires disease. It is emerging as an antibacterial resistant strain day by day. Hence, the identification of novel drug targets and vaccine candidates is essential to fight against this pathogen. Herein attempts were taken through subtractive genomics approach on complete proteome of L. pneumophila to address the challenges of multidrug resistance. A total 2930 proteins from L. pneumophila proteome were investigated through diverse subtractive proteomics approaches, e.g., identification of human non-homologous and pathogen-specific essential proteins, druggability and anti-target analysis, prediction of subcellular localization, human microbiome non-homology screening, protein-protein interactions studies in order to find out effective drug and vaccine targets. Only 3 were identified that fulfilled all these criteria and proposed as novel drug targets against L. pneumophila. Furthermore, outer membrane protein TolB was identified as potential vaccine target with better antigenicity score and allowed for further in silico analysis to design a unique multiepitope subunit vaccine against it. Antigenicity and transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis, and molecular docking approach were adopted to generate the most potent epitopes. The final vaccine was constructed by the combination of highly immunogenic epitopes along with suitable adjuvant and linkers. The designed vaccine construct showed higher binding interaction with different MHC molecules and human immune TLR2 receptors with minimum deformability at molecular level. The translational potency and microbial expression of the vaccine protein was also analyzed using pET28a(+) vector. The present study aids in the development of novel therapeutics and vaccine candidates for efficient treatment of the infections caused by Legionella pneumophila. However, further wet lab-based investigations and in vivo trials are highly recommended to experimentally validate our prediction.

bioinformatics↗