Biology subjects

Azad, A. K.

Publications and source records attributed to Azad, A. K..

4 recordsLinked to original sources

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↗

bioRxiv2023

HIV Infection impairs the Host Response to Mycobacterium tuberculosis Infection by altering Surfactant Protein D function in the Human Lung Alveolar Mucosa

Tuberculosis is the leading cause of death for people living with HIV (PLWH). We hypothesized that altered functions of innate immune components in the human alveolar lining fluid of PLWH (HIV-ALF), drive susceptibility to Mycobacterium tuberculosis (M.tb) infection. Our results indicate a significant increase in oxidation of innate proteins and chemokine levels, and significantly lower levels and function of complement components and Th1/Th2/Th17 cytokines in HIV-ALF vs. control-ALF (non-HIV infected people). We further found a deficiency of surfactant protein-D (SP-D) and reduced binding of SP-D to M.tb that had been exposed to HIV-ALF. Primary human macrophages infected with M.tb exposed to HIV-ALF were significantly less capable of controlling the infection, which was reversed by SP-D replenishment in HIV-ALF. Thus, our data suggest that PLWH without antiretroviral therapy (ART) have declining host innate defense function in their lung mucosa, thereby favoring M.tb and potentially other pulmonary infections.

cell biology↗

bioRxiv2022

Short communication: Antibiotic resistance in Gram-negative bacteria isolated from street-vended foods in Bangladesh

Antibiotic-resistant pathogens disseminated through food are a public health concern. Although a significant proportion of the urban population in developing countries consume street-vended foods, their role in spreading antibiotic resistance has been rarely investigated. In this study, we evaluated the antibiotic resistance patterns of bacterial isolates (n = 50) collected from five categories of street-vended foods (phuchka, chatpati, sausage, bun, and salad) in Bangladesh. Antibiotic susceptibility to twelve antibiotics was investigated by the Kirby-Bauer disk diffusion method. We found a high prevalence of E. coli (n = 32) in street-vended foods, with most isolates (65.63%) exhibiting multidrug resistance. The multiple antibiotic resistance (MAR) index showed that 22 isolates had MAR above 0.2, with resistance mostly against oxacillin, ampicillin, and cefuroxime. From the rest, three representative isolates were selected for molecular identification by DNA sequencing of 16S rDNA. Klebsiella oxytoca showed multiple drug resistance (MDR) and was resistant to ampicillin, oxacillin, cefuroxime, and kanamycin. Burkholderia fungorum showed no distinct inhibition zone against ampicillin and chloramphenicol. Additionally, the Serratia nematodiphila isolate showed no distinct inhibition zone against three antibiotics, including ampicillin, oxacillin, and cefuroxime. These findings might contribute to the knowledge of emerging antibiotic-resistant foodborne pathogens and raise concerns about the safety of street-vended foods in Bangladesh.

microbiology↗

bioRxiv2022

Human alveolar macrophage response to Mycobacterium tuberculosis: immune characteristics underlying large inter-individual variability

Mycobacterium tuberculosis (M.tb) establishes residence and growth in human alveolar macrophages (AMs). Large inter-individual variation in M.tb-AM interactions is a potential early indicator of TB risk and efficacy of therapies and vaccines. Herein, we systematically analyze interactions of a virulent M.tb strain with freshly isolated human AMs from 28 healthy adult donors, measuring host RNA expression and secreted candidate proteins associated with TB pathogenesis over 72h. We observe large inter-individual differences in bacterial uptake and growth, with tenfold variation in M.tb load at 72h, reflected by large variation of gene expression programs. Systems analysis of differential and variable RNA and protein expression identifies TB-associated genes and networks (e.g., IL1B and IDO1). RNA time profiles document early stimulation of M1-type macrophage gene expression followed by emergence of an M2-type profile. The fine-scale resolution of this work enables the separation of genes and networks regulating early M.tb growth dynamics, and development of potential markers of individual susceptibility to M.tb infection and response to therapies.

systems biology↗