Biology subjects

Deka, N.

Publications and source records attributed to Deka, N..

12 recordsLinked to original sources

bioRxiv2026

Optimized Urine Metagenomic Methods Reveal Longitudinal Microbial Community Dynamics and Predictors of Transition from Asymptomatic Colonization to CAUTI

BackgroundUrinary tract infections (UTIs) rank among the most common infections globally, with many linked to indwelling urinary catheters. Our prior culture-based longitudinal evaluation of long-term catheterized nursing home residents revealed persistent asymptomatic colonization by pathogens and demonstrated that CAUTI onset was not necessarily due to new pathogen acquisition. In this study, we optimized metagenomics methods to examine the ecological structure underlying persistent colonization and the transition to infection. ResultsWe present a comprehensive longitudinal metagenomic analysis of catheterized urine specimens, revealing colonization dynamics of 69 microbial species across 198 samples from 9 individuals. Descriptive ecological metrics were combined with Bayesian mixed-effects models that accounted for repeated within-participant sampling to identify clusters of co-occurring species, determine the impact of perturbations such as antibiotic exposure and catheter changes on community structure, and identify taxa predictive of infection sign and symptom onset. Longitudinal specimens clustered into three main ecological phenotypes: 1) moderate diversity, unstable communities (3 participants); 2) high diversity, stable communities that resisted disruption even after multiple catheter changes (3 participants); and 3) low diversity, pathogen-dominated communities (3 participants). Catheter changes alone did not significantly disrupt community composition, while antibiotic exposures induced major shifts often followed by re-colonization with the same genera within subsequent weeks. Six clusters of species were identified for which relative abundances correlated across perturbations to the microbial community, including a mutually exclusive Enterobacterales cluster and fastidious-anaerobe group cluster. 24 species were found to correlate with onset of signs and symptoms of infection, 11 of which were missed by standard urine culture. ConclusionsThe catheterized urinary tract represents a novel ecosystem that is resilient to disruption by catheter changes but susceptible to antibiotic perturbation. Antibiotic exposure did deplete all species associated with signs and symptoms but also depleted potentially benign microbes. Our findings have direct implications for catheter management protocols and antibiotic stewardship in long-term catheterized patients. Prospective evaluation using this framework in a larger cohort can help translate these ecological insights into clinical decision-making tools.

microbiology↗

bioRxiv2026

L Fucose Dependent Biofilm Formation by Escherichia coli Enhances Polymicrobial Interactions and Antibiotic Tolerance on Urinary Catheters

Urinary tract infections are common healthcare associated infections, a large subset of which are caused by indwelling catheters. Long term catheterization causes persistent, asymptomatic, polymicrobial colonization despite catheters changes and antibiotic usage. In these polymicrobial populations, P. mirabilis, E. faecalis, and E. coli were found as the most common co-colonizing species. We investigated how interactions between P. mirabilis, E. coli, and E. faecalis contribute to biofilm formation and colonization of urinary catheters. Our results show that the interaction between these three species leads to enhanced biofilm biomass driven by an increase in total protein content of the biofilm. Biofilm enhancement required all three species and was also media-dependent, especially for dual-species combinations. Importantly, triple species biofilms also demonstrate biofilm enhancement when established under flow conditions in a biofilm reactor model using silicone urinary catheters. Additionally, triple species biofilm enhancement occurred in co-colonizing isolates from catheterized patients and was found to be specific to interactions between these three species. Triple species biofilms also demonstrated a species-dependent resistance to two commonly used antibiotics, ciprofloxacin and nitrofurantoin. By examining priority effects, E. coli was found to be the main facilitator of biofilm enhancement in a flow model. Finally, proteomics revealed that an L-fucose utilization pathway in E. coli was a key contributor to triple species biofilm enhancement. Overall, our results demonstrate the significant impact of polymicrobial interactions on biofilm formation in the catheterized environment and highlight ways in which complex microbial interplay and priority effects can shape the establishment of persistent colonization.

microbiology↗

bioRxiv2026

Expression-dependent but strand-independent synonymous single-nucleotide polymorphism in the Escherichia coli chromosome

AbstractMutation in genomes is mainly attributed to replication, though transcription is also known to be mutagenic and is a more frequent event than replication in an organism. Recently, there have been reports regarding genome-wide transcription-induced mutagenesis. However, a distinct demonstration of specific mutation being replication-dependent and/or transcription-dependent in genomes is yet to be established. Here, we studied synonymous single-nucleotide polymorphisms (SNPs) in 2091 individual coding sequences (CDS) in the leading strand (LeS) and the lagging strand (LaS) of the Escherichia coli chromosome by comparing across 157 strains. The frequencies of complementary transitions (ti) and complementary transversions (tv) were compared in each CDS to assess parity violation in the context of strand location and gene expression. The C[->]T and G[->]A exhibited the maximum frequency as well as the most prominent strand inequality as these tis were influenced both by the strand location as well as by the gene expression. Interestingly, inequality between T[->]C and A[->]G was expression-dependent but strand-independent. This was a direct demonstration of strand inequality due to expression but not due to replication. A[->]T and G[->]T tvs were universally more frequent than their complementary T[->]A and C[->]A, respectively. The strand-independent but expression-dependent synonymous SNP inequality in CDS, supports the role of transcription-induced mutagenesis contributing to strand inequality in the E. coli chromosome. Significance StatementMutational patterns in bacterial genomes are shaped by both replication and transcription, but their relative roles remain unclear. By analyzing synonymous SNPs across 157 strains of E. coli, we identify strong strand-specific asymmetry consistent with replication-associated biases. A strong asymmetry between the strands regarding C[->]T and G[->]A ti is observed, as it is influenced by replication asymmetry and expression. We further show that gene expression significantly influences mutation types, with T[->]C ti being enriched in the highly expressed genes and A[->]G ti being enriched in the lowly expressed genes. Notably, A[->]T ti is strand independent but exhibits mild dependency on gene expression, revealing a previously unrecognized mutational pattern. These findings highlight how some SNPs are influenced by transcription but not replication

evolutionary biology↗

bioRxiv2026

Chondroitin sulfate degradation bolsters Proteus mirabilis growth and colonization of the catheterized urinary tract

Glycosaminoglycans (GAGs) are negatively charged polysaccharides composed of repeating disaccharide units and are essential components of the extracellular matrix throughout numerous tissues. The bladder urothelium has a thick protective GAG layer that primarily consists of chondroitin sulfate (CS), heparan sulfate (HS), and hyaluronic acid (HA), and urinary tract pathogens must either degrade or otherwise circumvent this layer to infect the urothelium. In this study, we investigated GAG degradation by Proteus mirabilis, a common and persistent colonizer of the catheterized urinary tract. Almost all P. mirabilis urinary tract isolates harbor a putative chondroitin endolyase (PMI2127), exolyase (PMI2128), and sulfatase (PMI2124). By generating mutant and complemented strains of these genes, we determined that P. mirabilis strain HI4320 degrades multiple forms of CS under numerous culture conditions, including during growth in human urine, and can use CS degradation products as a carbon source. Sulfatase and endolyase activity were required for efficient degradation of all CS types, while the exolyase only contributed to using CS-B or CS-C as carbon source. Interestingly, only endolyase activity contributed to colonization in a murine model of CAUTI, although the colonization defect was even more pronounced when the endolyase and exolyase were both disrupted. The colonization defect was specific to the CAUTI model, likely due to the impact of catheterization on the GAG landscape of the bladder. Limiting CS degradation by P. mirabilis may therefore represent a strategy for reducing risk of ascending infection in catheterized patients. ImportanceGlycosaminoglycans (GAGs) are a family of negatively charged heteropolysaccharides that are ubiquitously expressed throughout the body, forming a significant component of the extracellular matrix and a luminal GAG layer in the bladder. This GAG layer functions as a physical barrier for the bladder surface, protecting it from bacterial infection. Disruption of this barrier through physical forces, such as catheter insertion, or enzymatic degradation by bacteria may contribute to infection outcomes. In this study, we defined the contribution of three putative chondroitin sulfate degrading enzymes (PMI2124, PMI2127, PMI2128) to the pathogenesis of a common pathogen in the catharized urinary tract, Proteus mirabilis. We found that P. mirabilis can utilize chondroitin sulfate as a carbon source, and that chondroitin sulfate degradation contributes to infection in a model of catheterized urinary tract infection. This work contributes to a growing understanding of how uropathogens subvert host defenses and acquire nutrients within the bladder.

microbiology↗

bioRxiv2025

Pangenome Analysis of Proteus mirabilis Reveals Lineage-Specific Antimicrobial Resistance Profiles and Discordant Genotype-Phenotype Correlations

Urinary tract infections (UTIs) impose a large healthcare burden, with escalating antimicrobial resistance (AMR) and treatment failure. Proteus mirabilis is an under-characterized and challenging UTI pathogen due to intrinsic resistances and biofilm formation. To understand P. mirabilis population genomics, we combined pangenome analysis, in silico AMR predication, and phenotypic antimicrobial susceptibility testing (AST) across 1,027 P. mirabilis genomes derived from human urine specimens. This revealed a mosaic pangenome driven by extensive accessory genome plasticity. Multilocus sequence typing (MLST) identified 213 MLSTs with only 7% having [≥]10 genomes, highlighting strain diversity. AMR gene profiles were largely lineage specific, with 25% of genomes harboring resistances for >6 antimicrobial subclasses. ST135 was identified as a highly MDR lineage, with 95% of genomes carrying [≥]16 resistance genes. Mobile genetic element (MGE) analysis of 22 clinical isolates with complete, reference level genomes revealed that Tn7 transposons, IS26-mediated genomic islands, and class 1 integrons act as vehicles for high AMR gene dissemination, including IS26-mediated gene stacking within a Proteus mirabilis Genomic Resistance Island 1 (PmGRI1) in ST135 isolates. While presence of genes like aph(3)-la reliably predicted kanamycin resistance, discordance for antibiotics such as trimethoprim-sulfamethoxazole and chloramphenicol revealed that AMR gene stacking, regulatory context, and intrinsic mechanisms, like efflux pumps, modulate phenotypic outcomes. In summary, our study provides a comprehensive and phenotypic resolution of P. mirabilis AMR, establishing that resistance architecture is lineage structured, MGE-driven, and phenotypically non-deterministic. We emphasize the need to shift towards standardized, genome-informed surveillance framework to translate into diagnostic and therapeutic strategies.

microbiology↗

bioRxiv2025

Silent Speech Recognition with Wearable Magnetometers

Next-generation human-computer interaction (HCI) is moving towards more seamless, intuitive, and personal modes of communication, redefining how we interact with technology and one another. Within this landscape, silent speech recognition (SSR) offers a powerful new interaction paradigm, enabling hands-free, private interaction while supporting individuals with speech impairments and enabling communication in noisy or sensitive environments. Recent advances in miniaturized sensors and artificial intelligence (AI) have accelerated the development of more sophisticated wearable SSR systems, driven by growing demand for effortless and accessible communication. Although electrophysiological (ExG) modalities, particularly electromyography (EMG), have dominated early efforts in developing wearable SSR, critical challenges remain. Limited generalizability across users, sensor-skin interface issues, and difficulties with the comfort of use are all current roadblocks to reliable, high-fidelity signals in a wearable form factor. We propose that magnetometers offer a promising alternative to ExG and have the potential to unlock more robust, generalizable, and user-friendly SSR systems. We demonstrate that magnetometers embedded in a headphone form factor achieve a per-user SSR accuracy of 86%, significantly outperforming previously reported state-of-the-art wearable headphones combining ExG and inertial measurement units (IMUs). In addition, we show that wearable magnetometry enables generalization across individuals for SSR. Extending beyond headphones, we also introduce a necklace form factor with magnetometers that is capable of decoding both silent and overt speech in ambient conditions, further showcasing the versatility of magnetometers across different wearable designs in real-world conditions.

neuroscience↗

bioRxiv2024

Higher frequency of transition mutation over transversion mutation in genomes: evidence from the binding energy calculation of base pairs using DFT

Base substitution mutations such as transition (ti) and transversion (tv) in organisms are major driving force in molecular evolution. In this study, different possible types of base pairing that can cause ti and tv were investigated using the density functional theory (DFT) method. The chemical structures of bases as well as base pairs were optimized using B3LYP hybrid functional along with 6-31G(d,p) basis set. We performed single point energy calculation of all optimized species using the same functional but combined with higher diffuse and polarized basis set i.e. 6-311++G(d,p) to get more refined energy of all species. The binding energy of various base pairs was calculated considering basis set superposition error (BSSE) as well as without BSSE. The binding energy of the base pairs leading to ti was found to be more stable than that of the base pairs leading to tv. This was interesting considering the observations in organisms that tis are more frequent than tvs. Among the base pairs leading to the same ti, G(keto): T (enol) base pair was found to be more stable than A(imino):C(amino) base pair. This theoretical study of binding energy of different base pairs using the DFT method has provided additional evidences in support to the biological observations of a higher transition rate than transversion in genomes.

molecular biology↗

bioRxiv2024

The impact of fold-dilution and diluent volume on the estimation of colony forming units in a bacterial culture

Considering the non-uniform distribution of bacteria in a liquid culture, accurate enumeration of bacteria by serial dilution is important yet challenging in microbiological research. The deviation of estimated population size from the actual population size is anticipated in view of the sampling error arising at dilution, which is known to increase at each successive dilution; and the sampling error associated with the sample volume, where it is inversely proportional. In the dilution process of such population following a Poisson distribution, the relation of sampling error with the sequentially diluted suspensions is yet to be empirically demonstrated. Also, as a given-fold dilution can be achieved by passaging of either a higher or a lower sample volume, the sampling error associated in this case with the volume being passaged also remains to be evaluated. In view of that, the current experimental study was undertaken to further understand bacterial distribution and the underlying sampling error in dimensions previously not demonstrated. We demonstrated that sampling error in the enumeration process is independent of the bacterial cell densities of the diluted suspensions, which was on contrary to the theoretical assumptions. Moreover, sampling error is also not dependent on the number of passages in the dilution process. Importantly, we also demonstrated that passaging either a higher or lower sample volumes during serial dilution yielded similar enumeration, which was exceptional with regards to the statistical fluctuations inherent to a Poisson distribution.

microbiology↗

bioRxiv2024

Generalizable gesture recognition usingmagnetomyography

The progression of human-computer interfaces into immersive and touchless realities requires new ways of interacting with machines that are correspondingly intuitive and seamless. Among these are gesture-based systems that use natural hand movements to interact with and control digital devices. Today, these systems are most commonly implemented through the use of cameras or inertial sensors, which have drawbacks in environments that are poorly lit, in conditions where the hands are obscured, or for applications that require fine motor control. More recent studies have advocated for the use of surface electromyography (sEMG) to capture gesture information by sensing electrical activity generated by muscle contraction. While promising demonstrations have been shown, studies have also outlined limitations in sEMG when it comes to generalization across a population, largely due to physiological differences between individuals. Magnetomyography (MMG) is an alternative modality for measuring the same motor signals at the muscle, but is impervious to distortions caused by tissue, hair, and moisture; this indicates potential for lower variability caused by physiological differences and changes in skin conductivity, making MMG a promising generalizable solution for gesture control. To test this theory, we developed wristbands with magnetic sensors and implemented a signal processing pipeline for gesture classification. Using this system, we measured MMG across 30 participants performing a gesture task consisting of nine discrete gestures. We demonstrate average single-participant classification accuracy of 95.4%, rivaling state-of-the-art accuracy with sEMG. In addition, we achieved higher cross-session and cross-participant accuracy compared to sEMG studies. Given that these results were obtained with a non-ideal recording system, we anticipate significantly better results with better sensors. Together, these findings suggest that MMG can provide higher performance for control systems based on gesture recognition by overcoming limitations of existing techniques.

neuroscience↗

bioRxiv2024

Magnetomyography: A novel modality for non-invasive muscle sensing

The measurement of magnetic fields generated by skeletal muscle activity, called magnetomyography (MMG), has seen renewed interest from the academic community in recent years. Although studies have demonstrated complex models of MMG and experiments classifying between different movements using MMG, there has yet to be time frequency analysis of MMG as well as concurrent recordings of MMG and its electrical counterpart, surface electromyography (sEMG). Here, we aim to better understand MMG in the context of sEMG by simultaneously recording both modalities during various muscle contraction tasks. We found that, similar to sEMG, MMG shows highly linearly correlated power to the degree of muscle contraction, has a unimodal distribution in spectral power, and can detect changes in muscle fatigue via changes in the spectral distribution. One main difference we found was that MMG typically has more high frequency content compared to sEMG, even when accounting for the filtering induced by the size of the sEMG electrodes. We additionally demonstrate empirically the decrease in MMG power due to distance from the arm and show MMG decreases slower than the inverse square law and can be measured up to 50 mm from the surface of the skin. Finally, we were able to capture MMG with non-OPM sensors showing that sensor technology has made great strides towards enabling MMG applications.

neuroscience↗

bioRxiv2023

Incidences of Helicobacter infection in pigs and tracing occupational hazard in pig farmers

Helicobacter species (H. sp.) is a gram-negative spiral-shaped motile bacteria that causes gastritis in pigs and also colonizes the human stomach. The current study seeks to assess the prevalence of various H. sp. in the gastric mucosa of slaughtered and dead pigs, as well as the prevalence of Helicobacter infection among pig farmers. A total of 403 stomach samples from various pig slaughter points, 74 necropsy samples from various pig farms and 97 stool samples from pig farmers were collected from Assam, India. Among 477 pig stomach samples tested, 214 samples with gastritis (20.09%) showed Gram negative, spiral-shaped organisms in brush cytology from the mucosal surface, and the rest of the 263 stomach samples without any gastric lesion showed only 3.04% Gram negative, spiral-shaped organisms. In ultrastructure investigation, Scanning Electron Microscopy (SEM) of the four urease positive stomach samples revealed a tightly coiled Helicobacter bacterium (spiral-shaped) found in the mucous lining of the stomach. In histopathological examination of pars esophagia, cardiac and fundic mucosa showed chronic gastritis associated with hemorrhagic necrosis, leucocytic infiltration with neutrophils and macrophages, and lymphoid aggregates (lymphoid follicles) etc. PCR confirmed 16S rRNA genes of Helicobacter suis (H. suis) where a total of 42 (19.63%) out of 214 pig stomach samples and 2 (2.08%) out of 96 stool samples of pig farmers were found positive for H. suis. of these 96 stool samples of pig farmers 3 (3.12%) were confirmed positive for Helicobacter pylori (H. pylori) Phosphoglucosamine mutase gene in PCR. Phylogenic analysis of the 16S rRNA gene of H. suis showed distinct clusters with other H. sp. In conclusion, this study provides evidence for the prevalence of Helicobacter both in pig gastric mucosa and human stool. The findings highlight the need for improved sanitation and hygiene practices among pig farmers to minimize the risk of Helicobacter infection in humans.

microbiology↗

bioRxiv2022

Preferential catabolism of L- vs D-serine by Proteus mirabilis contributes to pathogenesis and catheter-associated urinary tract infection

Proteus mirabilis is a common cause of urinary tract infection, especially in catheterized individuals. Amino acids are the predominant nutrient for bacteria during growth in urine, and our prior studies identified several amino acid import and catabolism genes as fitness factors for P. mirabilis catheter-associated urinary tract infection (CAUTI), particularly D- and L-serine. In this study, we sought to determine the hierarchy of amino acid utilization by P. mirabilis and to examine the relative importance of D- vs L-serine catabolism for critical steps in CAUTI development and progression. Herein, we show that P. mirabilis preferentially catabolizes L-serine during growth in human urine, followed by D-serine, threonine, tyrosine, glutamine, tryptophan, and phenylalanine. Independently disrupting catabolism of either D- or L-serine has minimal impact on in vitro phenotypes while completely disrupting both pathways decreases motility, biofilm formation, and fitness due to perturbation of membrane potential and cell wall biosynthesis. In a mouse model of CAUTI, loss of either serine catabolism system decreased fitness, but disrupting L-serine catabolism caused a greater fitness defect than disrupting D-serine catabolism. We therefore conclude that hierarchical utilization of amino acids may be a critical component of P. mirabilis colonization and pathogenesis within the urinary tract. Abbreviated SummaryAmino acids are a predominant nutrient in urine, and their import and catabolism has been hypothesized to contribute to the ability of bacteria to cause urinary tract infection. We demonstrate that a common uropathogen, Proteus mirabilis, preferentially catabolizes L-serine followed by D-serine, threonine, tyrosine, and glutamine during growth in human urine. We further demonstrate that L-serine catabolism provides a greater fitness advantage than D-serine catabolism, yet both pathways contribute to pathogenesis in the urinary tract. Graphical Abstract(Created using BioRender.com) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/494593v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@13f3286org.highwire.dtl.DTLVardef@e0e84org.highwire.dtl.DTLVardef@db2946org.highwire.dtl.DTLVardef@72b421_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗