Biology subjects

Sarkar, M. M. H.

Publications and source records attributed to Sarkar, M. M. H..

4 recordsLinked to original sources

bioRxiv2024

Genomic characterization and functional insights of multidrug-resistant Klebsiella pneumoniae strain BCSIR-JUMIID

Klebsiella pneumoniae is a prominent opportunistic pathogen associated with multidrug resistance (MDR) and high morbidity and mortality rates in healthcare settings. The emergence of strains resistant to last-resort antibiotics, such as colistin and carbapenems, poses significant therapeutic challenges. This study presents the complete genome analysis of the MDR strain K. pneumoniae BCSIR-JUMIID to elucidate its genetic architecture, resistance mechanisms, and virulence factors. The genome of K. pneumoniae BCSIR-JUMIID, isolated from a pharmaceutical wastewater in Dhaka, Bangladesh, was sequenced using next-generation sequencing technologies. Bioinformatics tools were employed for genome assembly, annotation, and functional analysis. Phylogenetic relationships were established through whole-genome comparisons. Antibiotic resistance genes, virulence factors, and mobile genetic elements were identified using the Comprehensive Antibiotic Resistance Database (CARD), ResFinder-4.5.0, Virulence Factors Database (VFDB), and various phage identification tools. The genome of K. pneumoniae BCSIR-JUMIID consists of 5,769,218 bp with a G+C content of 56.79%, assembled into 343 contigs. A total of 6,062 coding sequences (CDS), including 1,087 hypothetical proteins, 49 tRNA genes, and 4 rRNA genes, were identified. Key loci involved in capsular polysaccharide and O-antigen biosynthesis (KL150, KL107-D1, O3b) were detected. A diverse array of antibiotic resistance genes was uncovered, including those conferring resistance to beta-lactams, quinolones, and colistin. Phage analysis revealed the presence of multiple dsDNA bacteriophages, and CRISPR-Cas systems indicated robust phage defense mechanisms. The genomic analysis of K. pneumoniae BCSIR-JUMIID provides a detailed understanding of its resistance and virulence mechanisms, highlighting its potential for horizontal gene transfer and rapid adaptation. These findings underscore the necessity for continued surveillance and novel therapeutic strategies to combat MDR K. pneumoniae infections effectively.

microbiology↗

bioRxiv2022

Comparative Phylogenetic Analysis and Transcriptomic Profiling of Dengue (DENV-3 genotype I) Outbreak in 2021 in Bangladesh

ObjectivesThe lack of a dengue disease animal model and the complex immune interaction in dengue infection hinders the study of host response and immunopathogenesis. The development of next-generation sequencing (NGS) technology allowed the researchers to study the transcriptomic profiles of human in-depth. We, therefore, implicated phylodynamic and transcriptomic approaches through NGS technology to know the origin of dengue virus (DENV) and their host response in infected patients with dengue fever. MethodsTo determine the whole genome sequences of the dengue virus and their transcriptomic profiles, RNA was extracted from the serum samples of 3 healthy, and 21 dengue patients. These samples were custom performed at phylogenetic, phylodynamic, differential express gene (DEG), and gene ontology (GO) using respective bioinformatics tools. ResultsThe whole genome sequence analysis revealed that the total number of nucleotide ranges on these serum RNA samples were in between 10647 and 10707. Phylogenetic tree analysis showed that these strains were belonged to DENV-3 genotype I. Phylodynamic analysis showed that the 2021 epidemic isolates were clade shifted and maintained as a new clade in compared to 2019 epidemic. Transcriptome analysis mapped a total of 19267 expressed genes. Of them, there were higher expression of genes in dengue-positive samples (n = 17375) with a count of 6953 unique genes in comparison to healthy controls (n = 12314) with a count of 1892 unique genes. A total of 2686 DEGs were identified in a host factor-independent manner in dengue patients with a q-value < 0.05. DESeq2 plot counts function of the top 24 genes with the smallest q-values of differential gene expression of RNA-seq data showed that 11 genes were upregulated, whereas 13 genes were downregulated. GO analysis showed a significant upregulation (p = <0.001) in a process of multicellular organismal, nervous system, sensory perception of chemical stimulus, and G protein-coupled receptor signalling pathways in the dengue patients. However, there were a significant downregulation (p = < 0.001) of intracellular component, cellular anatomical entity, and protein-containing complex in dengue patients. Most importantly, there was significant increase of a classes of immunity protein (Cytokines especially TGF-{beta}1, chemokines, inflammasome, and factors for blood coagulations) in dengue patients in compared to the healthy controls, with increased GO of immune system process. In addition, upregulation of toll receptor (TLR) signalling pathways were also initiated in the patients infected with dengue virus. These TLR pathways were particularly involved for the activation of innate in couple with adaptive immune system that probably involved the rapid elimination of dengue virus infected cells. These differentially expressed genes could be further investigated for target based prophylactic interventions for dengue. ConclusionThis is a first report to document the complete genomic features of dengue, and differentially expressed genes in patients with dengue virus in Bangladesh. These genes may have diagnostic and therapeutic values for dengue infection. Continual genomic surveillance is required to further investigate the shift in dominant genotypes in relation to viral pathogenesis.

evolutionary biology↗

bioRxiv2022

Metagenomic analysis reveals the abundance and diversity of opportunistic fungal pathogens in the nasopharyngeal tract of COVID-19 patients

The nasopharyngeal tract (NT) of human is a habitat of a diverse microbial community that work together with other gut microbes to maintain the host immunity. In our previous study, we reported that SARS-CoV-2 infection reduces human nasopharyngeal commensal microbiome (bacteria, archaea and commensal respiratory viruses) but increases the abundance of pathobionts. This study aimed to assess the possible changes in the resident fungal diversity by the inclusion of opportunistic fungi due to the infection of SARS-CoV-2 in the NT of humans. Twenty-two (n = 22) nasopharyngeal swab samples (including COVID-19 = 8, Recovered = 7, and Healthy = 7) were collected for RNAseq-based metagenomics analyses. Our results indicate that SARS-CoV-2 infection significantly increased (p < 0.05, Wilcoxon test) the population and diversity of NT fungi with a high inclusion of opportunistic pathogens. We detected 863 fungal species including 533, 445, and 188 species in COVID-19, Recovered, and Healthy individuals, respectively that indicate a distinct microbiome dysbiosis due to the SARS-CoV-2 infection. Remarkably, 37% of the fungal species were exclusively associated with SARS-CoV-2 infection, where S. cerevisiae (88.62%) and Phaffia rhodozyma (10.30%) were two top abundant species in the NT of COVID-19 patients. Importantly, 16% commensal fungal species found in the Healthy control were not detected in either COVID-19 patients or when they were recovered from the COVID-19. Pairwise Spearmans correlation test showed that several altered metabolic pathways had significant positive correlations (r > 0.5, p < 0.01) with dominant fungal species detected in three metagenomes. Taken together, our results indicate that SARS-CoV-2 infection causes significant dysbiosis of fungal microbiome and alters some metabolic pathways and expression of genes in the NT of human. Findings of our study might be helpful for developing microbiome-based diagnostics, and also devising appropriate therapeutic regimens including antifungal drugs for prevention and control of concurrent fungal coinfections in COVID-19 patients. Author summaryThe SARS-CoV-2 is a highly transmissible and pathogenic betacoronavirus that primarily enters into the human body through NT to cause fearsome COVID-19 disease. Recent high throughput sequencing and downstream bioinformatic analyses revealed that microbiome dysbiosis associated with SARS-CoV-2 infection are not limited to bacteria, and fungi are also implicated in COVID-19 development in susceptible individuals. This study demonstrates that SARS-CoV-2 infection results in remarkable depletion of NT commensal fungal microbiomes with inclusion of various opportunistic fungal pathogens. We discussed the role of these altered fungal microbiomes in the pathophysiology of the SARS-CoV-2 infection. Our results suggest that dysbiosis in fungal microbiomes and associated altered metabolic functional pathways (or genes) possibly play a determining role in the progression of SARS-CoV-2 pathogenesis. Thus, the identifiable changes in the diversity and composition of the NT fungal population and their related genomic features demonstrated in this study might lay a foundation for better understanding of the underlying mechanism of co-pathogenesis, and the ongoing development of therapeutic agents including antifungal drugs for the resolution of COVID-19 pandemic.

microbiology↗

bioRxiv2020

The genetic variants analysis of circulating SARS-CoV-2 in Bangladesh.

Genomic mutation of the virus may impact the viral adaptation to the local environment, their transmission, disease manifestation, and the effectiveness of existing treatment and vaccination. The objectives of this study were to characterize genomic variations, non-synonymous amino acid substitutions, especially in target proteins, mutation events per samples, mutation rate, and overall scenario of coronaviruses across the country. To investigate the genetic diversity, a total of 184 genomes of virus strains sampled from different divisions of Bangladesh with sampling dates between the 10th of May 2020 and the 27th of June 2020 were analyzed. To date, a total of 634 mutations located along the entire genome resulting in non-synonymous 274 amino acid substitutions in 22 different proteins were detected with nucleotide mutation rate estimated to be 23.715 substitutions per year. The highest non-synonymous amino acid substitutions were observed at 48 different positions of the papain-like protease (nsp3). Although no mutations were found in nsp7, nsp9, nsp10, and nsp11, yet orf1ab accounts for 56% of total mutations. Among the structural proteins, the highest non-synonymous amino acid substitution (at 36 positions) observed in spike proteins, in which 9 unique locations were detected relative to the global strains, including 516E>Q in the boundary of the ACE2 binding region. The most dominated variant G614 (95%) based in spike protein is circulating across the country with co-evolving other variants including L323 (94%) in RNA dependent RNA polymerase (RdRp), K203 (82%) and R204 (82%) in nucleocapsid, and F120 (78%) in NSP2. These variants are mostly seen as linked mutations and are part of a haplotype observed in Europe. Data suggest effective containment of clade G strains (4.8%) with sub-clusters GR 82.4%, and GH clade 6.4%. HighlightsO_LIWe have sequenced 137 and analyzed 184 whole-genomes sequences of SARS-CoV-2 strains from different divisions of Bangladesh. C_LIO_LIA total of 634 mutation sites across the SARS-CoV-2 genome and 274 non-synonymous amino acid substitutions were detected. C_LIO_LIThe mutation rate of SARS-CoV-2 estimated to be 23.715 nucleotide substitutions per year. C_LIO_LINine unique variants were detected based on non-anonymous amino acid substitutions in spike protein relative to the global SARS-CoV-2 strains. C_LI

genomics↗