Research Projects
3 Ongoing Projects
On Going Researches
1. Developing a phage bank in Bangladesh: a rapid and cost-effective tool to combat antimicrobial resistance in the developing world
The global rise of antibiotic resistance (AMR) poses a critical threat, particularly in lower- and middle-income countries (LMICs) that are expected to bear the highest burden of AMR-related deaths. Many LMICs depend on imported therapeutics from industrialized nations, a process often delayed by financial and supply chain constraints, as highlighted during the COVID-19 pandemic. Locally produced antibacterial therapies are therefore urgently needed. Bacteriophages (phages) provide a targeted and cost-effective alternative to conventional antibiotics. This study aims to establish a diverse, well-characterized phage collection in Bangladesh as a rapid, cost-effective, and environmentally friendly alternative to conventional antibiotics. To build this resource, phages were isolated from hospital sewage, clinical samples, farm effluents, and municipal drainage. The bacterial targets included Klebsiella pneumoniae, Escherichia coli, Klebsiella aerogenes, Salmonella typhimurium, Staphylococcus auricularis, Staphylococcus hemolyticus, Staphylococcus aureus, Enterobacter cloacae, Stenotrophomonas maltophilia, Bacillus subtilis, and Enterococcus faecalis. Phage characterization included multiplicity of infection (MOI) assays, one-step growth curve analyses, and stability testing under variable temperature and pH conditions. Biofilm-degrading potential was assessed using antibiotic-tolerant biofilm models. Whole-genome sequencing was performed for four representative phages to evaluate the presence of virulence or antibiotic resistance genes. Phages demonstrated efficient bacterial lysis at low MOI values and exhibited stable replication with defined latent and lysis periods. Many isolates remained active across broad temperature and pH ranges. Several phages displayed strong biofilm-disruptive activity, effectively lysing antibiotic-tolerant bacteria within biofilms. Genomic analysis confirmed the absence of undesirable genes, supporting their therapeutic safety. The growing phage bank, comprising environmentally stable, biofilm-active, and genomically safe isolates, represents a significant One Health resource for Bangladesh. This platform enables the rapid development of tailored phage therapies against multidrug-resistant pathogens in human, animal, and environmental sectors. By reducing reliance on imported therapeutics, this initiative offers a sustainable and scalable model for LMICs addressing the AMR crisis.
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2. 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.
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3. 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.
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