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Kamruzzaman, M.

Publications and source records attributed to Kamruzzaman, M..

9 recordsLinked to original sources

Specific exclusion of conjugative plasmids from the gut microflora

The rise of dangerous antimicrobial resistance (AMR), especially to the newer carbapenem antibiotics, is largely driven by the spread of conjugative plasmids between bacteria. These plasmids rapidly disseminate among common gut organisms like Escherichia coli and Klebsiella pneumoniae, which together account for around half of lethal sepsis and septic shock. Current AMR control measures, such as surveillance and isolation, are often ineffective, and AMR is often detected for the first time when infection is well established. Natural plasmid entry-exclusion systems (EES) protect bacterial populations from repeated entry by plasmids that are already established, or indeed by any plasmid with a related cognate EES, and we demonstrate here the exploitation of this mechanism for therapeutic purposes. We combined exclusion genes from three major AMR plasmid types (IncM, IncL, and IncC) into an efficient conjugative plasmid backbone and showed that this engineered probiotic plasmid prevents invasive AMR plasmids from entering bacterial populations in vitro and in vivo, in the mouse gut. This offers a promising new strategy to control invasive AMR plasmids and prevent AMR acquisition in high-risk settings, such as in hospitals or AMR-endemic regions.

microbiology↗

Hyperspectral Imaging to Quantify Nodules and Detect Biological Nitrogen Fixation in Legumes

Legume root nodules are important for biological nitrogen fixation, a process critical for plants to gain additional nitrogen from the environment. Nodule quantification is valuable for evaluating nitrogen fixation efficiency, assessing symbiotic relationships, monitoring responses to nitrogen, and supporting genetic studies on legume adaptation and productivity. However, accurate quantification of root nodules is difficult and time-consuming due to the complexity of the root system and soil interference. Here, we explore the utility of hyperspectral imaging as a non-destructive tool to detect active fixing root nodules with minimal preparation and show that we can differentiate nodules and root tissues through unique spectral signatures while also distinguishing between fixing and non-fixing nodules. We applied deep learning techniques to develop an automated nodule counting pipeline adaptable across different legume species and under diverse growth conditions. This approach eliminates the need for labor-intensive counting and enables the detection of nodules embedded within dense root tangles with high accuracy. This automated hyperspectral approach offers a promising alternative to support assessments of nodule abundance and their activity across legume species grown under various environments.

plant biology↗

Computational investigation unveils pathogenic LIG3 non-synonymous mutations and therapeutic targets in acute myeloid leukemia

Single nucleotide polymorphisms (SNPs) in DNA repair genes can impair protein structure and function, contributing to disease development, including cancer. Non-synonymous SNPs (nsSNPs) in the LIG3 gene are linked to genomic instability and increased cancer risk, particularly acute myeloid leukemia (AML). This study aims to identify the most deleterious nsSNPs in the LIG3 gene and potential therapeutic targets for DNA repair restoration in AML. We employed in-silico computational methods to analyze LIG3 nsSNPs, using PredictSNP and Mutation3D to assess pathogenicity. Subsequently, molecular docking and dynamics simulations were conducted to evaluate ligand-binding affinities and protein stability. Out of the 12,191 mapped SNPs, 132 were nsSNPs located in the coding region. Among these, 18 nsSNPs were identified as detrimental including 12 destabilizing and 6 stabilizing nsSNPs. Nine cancer-associated nsSNPs, including L381R and R528C, were predicted due to their structural and functional impacts. Further analysis revealed key phosphorylation and methylation sites, such as 529S and 224R. Molecular dynamics simulations highlighted stable interactions of compounds AHP-MPC and DM-BFC with wild-type and R528C mutant LIG3 proteins, while R671G and V781M mutants showed instability. Protein-protein interaction networks and functional enrichment linked LIG3 to DNA repair pathways. Kaplan-Meier analysis associated high LIG3 expression with improved survival in breast cancer and AML, suggesting its role as a prognostic biomarker. This study emphasizes the mutation-specific effects of LIG3 nsSNPs on protein stability and ligand interactions. We recommend identifying DM-BFC to advance personalized medicine approaches for targeting deleterious variants, following in vitro and in vivo validation for AML treatment.

cancer biology↗

Consolidated sustainable organic nanozyme integrated with Point-Of-Use sensing platform for dual agricultural and biological molecule detection

The newly introduced organic nanozymes offer a promising alternative to inorganic nanozymes by sustainable and cost-effective solutions. Given the potential of nanozyme-based Point-of-Care (PoC) systems for on-demand molecule sensing; these user-friendly Point-of-Use(PoU) platforms can be highly beneficial for real-world agricultural and biological applications. Herein, a novel, fully organic compound/monomer-based, sustainable organic nanozyme is introduced, that exhibits peroxidase-like enzyme-like catalytic activity. Utilizing a unique self-assembled particle fabrication process, homogenous nanozyme are fabricated within a short time (within 50 nm, D90), exhibiting decent kinetic profiles (Km= 0.046 mM, H2O2), and degradability for improved waste management after its use. OM nanozyme-incorporated colorimetric sensing platforms successfully detect popular agricultural toxic biomolecules and biological molecules while achieving decent molecule sensing performance (practical LOD, glyphosate: at least 1pgmL-1, glucose: 3.47 ngmL-1) with high analytical sensitivity and selectivity. Additionally, a smartphone image-based polynomial regression analysis system and paper-microfluidic hardware were developed to facilitate PoU applications in a lab-free environment with satisfactory analytic sensitivity (at least 1.6gmL-1, for glyphosate, and glucose). This sustainable OM nanozyme, coupled with the PoU platform, is envisioned to have broad applications in agricultural and biological systems.

bioengineering↗

Shigella O-specific polysaccharide functional IgA responses mediate protection against shigella infection in an endemic high-burden setting

Shigella is the second leading cause of diarrheal disease-related death in young children in low and middle income countries. The mechanism of protection against shigella infection and disease in endemic areas is uncertain. While historically LPS-specific IgG titers have been associated with protection in endemic settings, emerging deeper immune approaches have recently elucidated a protective role for IpaB-specific antibody responses in a controlled human challenge model in North American volunteers. To deeply interrogate potential correlates of immunity in areas endemic for shigellosis, here we applied a systems approach to analyze the serological response to shigella across endemic and non-endemic populations. Additionally, we analyzed shigella-specific antibody responses over time in the context of endemic resistance or breakthrough infections in a high shigella burden location. Individuals with endemic exposure to shigella possessed broad and functional antibody responses across both glycolipid and protein antigens compared to individuals from non-endemic regions. In high shigella burden settings, elevated levels of OSP-specific FcR binding antibodies were associated with resistance to shigellosis. OSP-specific FcR binding IgA found in resistant individuals activated bactericidal neutrophil functions including phagocytosis, degranulation and reactive oxygen species production. Moreover, IgA depletion from resistant serum significantly reduced binding of OSP-specific antibodies to FcR and antibody mediated activation of neutrophils and monocytes. Overall, our findings suggest that OSP-specific functional IgA responses contribute to protective immunity against shigella infection in high-burden settings. These findings will assist in the development and evaluation of shigella vaccines.

immunology↗

L-form switching confers antibiotic, phage and stress tolerance in pathogenic Escherichia coli

The bacterial L-form is induced by exposure to cell wall targeting antibiotics or innate immune effectors such as lysozyme and is likely to be important in many human infections. Here, we demonstrate that the osmotically fragile L-form is a distinct physiological state in Escherichia coli that is highly tolerant of oxidative stress and resistant to powerful antibiotics and common therapeutic bacteriophages. L-forms quickly revert (<20h) to their cell-walled state after antibiotic withdrawal, with apparently normal physiology and with few or no changes in DNA sequence. T4-like phages that are obligately lytic in cell-walled E. coli preferentially pseudolysogenise their L-forms providing them with transient superinfection immunity. Our data indicate that L-form switching is a common response of pathogenic E. coli strains to cell wall-targeting antibiotics and that the most commonly used lytic bacteriophages are ineffective against them in this state.

microbiology↗

Humans surviving cholera develop antibodies against Vibrio cholerae O-specific polysaccharide that inhibit pathogen motility

The mechanism of protection against cholera afforded by previous illness or vaccination is currently unknown. We have recently shown that antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae correlate highly with protection against cholera. V. cholerae is highly motile and possesses a flagellum sheathed in O-specific polysaccharide (OSP), and motility of V. cholerae correlates with virulence. Using high speed video microscopy, and building upon previous animal-related work, we demonstrate that sera, polyclonal antibody fractions, and OSP-specific monoclonal antibodies recovered from humans surviving cholera block V. cholerae motility at both subagglutinating and agglutinating concentrations. This anti-motility effect is reversed by pre-adsorbing sera and polyclonal antibody fractions with purified OSP; and is associated with OSP-specific but not flagellin-specific monoclonal antibodies. F[ab] fragments of OSP-specific polyclonal antibodies do not inhibit motility, suggesting a requirement for antibody-mediated crosslinking in motility inhibition. We show that OSP-specific antibodies do not directly affect V. cholerae viability, but that OSP-specific monoclonal antibody highly protects against death in the murine cholera model. We used in vivo competitive index studies to demonstrate that OSP-specific antibodies impede colonization and survival of V. cholerae in intestinal tissues, and that this impact is motility-dependent. Our findings suggest that the impedance of motility by antibodies targeting V. cholerae OSP contributes to protection against cholera. IMPORTANCECholera is a severe dehydrating illness of humans caused by Vibrio cholerae. V. cholerae is a highly motile bacterium that has a single flagellum covered in lipopolysaccharide (LPS) displaying O-specific polysaccharide (OSP), and V. cholerae motility correlates with its ability to cause disease. The mechanisms of protection against cholera are not well understood; however, since V. cholerae is a non-invasive intestinal pathogen, it is likely that antibodies that bind the pathogen or its products in the intestinal lumen contribute to protection from infection. Here, we demonstrate that OSP-specific antibodies isolated from humans surviving cholera in Bangladesh inhibit V. cholerae motility and are associated with protection against challenge in a motility-dependent manner.

microbiology↗

Specialised functions of two common plasmid mediated toxin-antitoxin systems, ccdAB and pemIK, in Enterobacteriaceae

Toxin-antitoxin systems (TAS) are commonly found on bacterial plasmids and are involved in plasmid maintenance. Even though the same TAS are present in a variety of plasmid types and bacterial species, differences in their sequences, expression and functions are not well defined. Here, we aimed to identify commonly occurring plasmid TAS in Escherichia coli and Klebsiella pneumoniae and compare the sequence, expression and plasmid stability function of their variants. 27 putative type II TAS were identified from 1063 plasmids of Klebsiella pneumoniae in GenBank. Among these, ccdAB and pemIK were found to be most common, also occurring in plasmids of E. coli. Comparisons of ccdAB variants, taken from E. coli and K. pneumoniae, revealed sequence differences, while pemIK variants from IncF and IncL/M plasmids were almost identical. Similarly, the expression and plasmid stability functions of ccdAB variants varied according to the host strain and species, whereas the expression and functions of pemIK variants were consistent among host strains. The specialised functions of some TAS may determine the host specificity and epidemiology of major antibiotic resistance plasmids.

microbiology↗

Toward A Scalable Exploratory Framework for Complex High-Dimensional Phenomics Data

Phenomics is an emerging branch of modern biology that uses high throughput phenotyping tools to capture multiple environmental and phenotypic traits, often at massive spatial and temporal scales. The resulting high dimensional data represent a treasure trove of information for providing an in-depth understanding of how multiple factors interact and contribute to the overall growth and behavior of different genotypes. However, computational tools that can parse through such complex data and aid in extracting plausible hypotheses are currently lacking. In this paper, we present Hyppo-X, a new algorithmic approach to visually explore complex phenomics data and in the process characterize the role of environment on phenotypic traits. We model the problem as one of unsupervised structure discovery, and use emerging principles from algebraic topology and graph theory for discovering higher-order structures of complex phenomics data. We present an open source software which has interactive visualization capabilities to facilitate data navigation and hypothesis formulation. We test and evaluate Hyppo-X on two real-world plant (maize) data sets. Our results demonstrate the ability of our approach to delineate divergent subpopulation-level behavior. Notably, our approach shows how environmental factors could influence phenotypic behavior, and how that effect varies across different genotypes and different time scales. To the best of our knowledge, this effort provides one of the first approaches to systematically formalize the problem of hypothesis extraction for phenomics data. Considering the infancy of the phenomics field, tools that help users explore complex data and extract plausible hypotheses in a data-guided manner will be critical to future advancements in the use of such data.

bioinformatics↗