Biology subjects

Hossain, S.

Publications and source records attributed to Hossain, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Participatory Systems Mapping and Experimental Games to Explore Biosecurity Adoption in Broiler Production in Bangladesh

IntroductionAntimicrobial Resistance (AMR) presents a critical public health challenge, particularly in smallholder broiler farming, where antibiotics are often used preventively in the absence of effective biosecurity measures. ObjectiveThis study investigates the adoption of biosecurity practices as a sustainable alternative to antibiotics through Participatory Systems Mapping and Experimental Games. MethodsA participatory mixed-methods study was conducted in southern Bangladesh (September 2024-June 2025). Causal Loop Diagrams (CLDs) were co-created with farmers, dealers, and veterinary officers. Ten broiler farmers from single village were selected via purposive and snowball sampling. Experimental games simulated four production cycles where farmers chose Option A (biosecurity, adopters) or Option B (antibiotics, non-adopters) after several interactive trainings. Key metrics including biosecurity compliance (0-12 scale), mortality, FCR, antibiotic use, outbreak history, and economic outcomes were recorded. ResultsCLD analysis revealed a reinforcing loop of increased antibiotic reliance driven by fear of mortality, and balancing loops involving training, biosecurity practices, and consumer incentives to reduce use. Five farmers chose Option A, and both groups remained stable until Round 4. Adopters had flock sizes of 800-2000 birds (non-adopters, 600-1000; mean for both = 1000), were younger, and more educated compared to non-adopters. At baseline, both groups had similar biosecurity scores (0). Adopters had higher mean outbreaks (2 vs. 1.4), mortality (5.6 vs. 4.2), antibiotic use (3.6 vs. 3), and FCR (1.8 vs. 1.6) compared to non-adopters. By Round 4, adopters improved biosecurity scores by 125%, eliminated outbreaks, reduced mortality by 52.6%, stopped antibiotic use, improved FCR by 13.3%, and gained 71.72% profit per bird compared to non-adopters. Non-adopters, influenced by adopters, increased biosecurity scores by 25%, reducing outbreaks, mortality, antibiotic use, and FCR. Adopters also increased direct sales to consumers, yielding a 10%-16% profit gain per bird each round. ConclusionThis study highlights the successful adoption of biosecurity practices by farmers, replacing antibiotics and improving production outcomes. Farmer-driven adoption of these practices fosters long-term sustainability and supports a healthier planet within the One Health framework.

microbiology↗

bioRxiv2026

In silico transcriptomic analysis reveals shared molecular signatures and immune-associated pathways between Hashimotos thyroiditis and type 2 diabetes with exploratory drug repurposing

The management of Hashimotos thyroiditis (HT), one of the most prevalent autoimmune disorders worldwide, becomes more complex when it coexists with type 2 diabetes (T2D) compared with the management of either disease alone. This complexity may arise from overlapping genetic, metabolic, and immune dysregulation, as well as potential therapeutic conflicts. Although HT and T2D are known to co-occur and share immune and metabolic features, the molecular characteristics underlying these overlaps have not been systematically explored. This study aimed to identify shared gene expression signatures and associated biological pathways between HT and T2D using an in silico, hypothesis-generating approach, and to explore candidate compounds that may be relevant to both conditions. Independent transcriptomic datasets (GSE138198 for control/HT and GSE29231 for control/T2D) were analyzed, leading to the identification of 59 genes that were differentially expressed in both HT and T2D compared with control samples. Protein-protein interaction (PPI) network analysis prioritized five shared key genes (sKGs): CDC42, CD74, FOS, RAC2, and YWHAB. Functional enrichment analysis of these sKGs revealed overlapping biological processes, molecular functions, cellular components, and immune-related signaling pathways, as well as shared regulatory networks involving transcription factors (FOXC1 and HNF4A) and microRNAs (hsa-miR-221-3p and hsa-miR-29a-3p). Immune infiltration analysis demonstrated broadly similar patterns of immune dysregulation in both diseases, providing additional biological context for the observed shared molecular signatures. Finally, an exploratory in silico drug repurposing pipeline incorporating molecular docking, ADMET profiling, drug-likeness assessment, and molecular dynamics simulations prioritized three candidate compounds: gliquidone, oleanolic acid, and glipizide for further investigation. Overall, this study provides a hypothesis-generating framework highlighting shared molecular features between HT and T2D, which may inform future experimental validation and clinical research. Author SummaryIn this work, we wanted to better understand why Hashimotos thyroiditis, an autoimmune condition that affects the thyroid gland, is often seen in people who also have type 2 diabetes. Treating patients who live with both conditions can be difficult, and we were interested in finding out whether they share common biological causes. To do this, we examined genetic data from individuals with each disease and looked for patterns that appeared in both groups. We discovered several genes that seem to act in similar ways in the two conditions, particularly genes linked to immune system activity and associated pathways. This finding suggests that shared molecular signatures and immune-associated pathways may play a role in the development of both diseases. We also explored how these shared genetic features influence larger biological processes and immune responses. The similarities we found support the idea that the two diseases may be connected through related biological pathways. In addition, we used computer-based screening methods to identify existing drugs that might influence these shared pathways. While these results need further testing, we hope our findings help open new directions for research and eventually contribute to better care for patients affected by both conditions.

bioinformatics↗

bioRxiv2026

A Course-Undergraduate Research Experience (CURE) to explore the effect of structural variants on gene expression in C. elegans balancers

Bioinformatics, a discipline at the crossroads of Biology and Computational Sciences, also referred to as Computational Biology, is nowadays widely spread in research programs. However, implementing any Bioinformatics projects requires the ability to comprehend biological concepts and apply computational approaches, and rare are the undergraduate programs offering such multi-disciplinary training. In addition, understanding the dynamic between Biology research projects and Bioinformatics analyses is challenging with no real-life experience. Course-based undergraduate research experience (CURE) courses are innovative programs that allow more students to acquire research experience and provide the perfect setting to introduce students to applied bioinformatics. As a part of the Bachelor of Health Sciences of the Cumming School of Medicine at the University of Calgary (Canada), a CURE applied bioinformatics was implemented in the Winter of 2023 to 2025. Students investigated the effect of structural variants (SVs, genetic variants larger than 50 bp) on gene expression in the model organism Caenorhabditis elegans (a hermaphrodite 1-mm long roundworm). The students detected and characterized SVs by analyzing genome and transcriptome sequencing data of C. elegans strains called balancers, as they are known to carry large genomic variations balancing regions of the genome by limiting recombination and allowing maintenance of lethal mutations. They used Galaxy, a public web-based supercomputing resource, but also a local High-Performance computing system, and R, to report different effects of SVs on gene expression and splicing. Students research explained the molecular mechanism behind the uncoordinated phenotype caused by the reciprocal translocation eT1(III;V) and uncovered unexpected effects on gene expression on an understudied gene. We evaluated the courses impact on student learning journeys and showed that the CURE favored students understanding of the Bioinformatics field and fostered their research interest. We provide here guidelines to facilitate the CURE implementations to improve access for undergraduate students to bioinformatics research experiences.

bioinformatics↗

bioRxiv2025

Commensal Escherichia coli colonization triggers Peyer's patch development

The gut microbiota plays a pivotal role in shaping mucosal immunity, yet the specific microbes contributing to lymphoid tissue development remain poorly defined. Here, we identify Escherichia coli, a pioneer commensal bacterium, as a key driver of naive B cell accumulation in gut Peyers patches and lamina propria via a CXCR2-dependent mechanism. We show that E. coli promotes B cell recruitment through the production of curli amyloid fibers, which signal via Toll-like receptor 2 (TLR2). Notably, this effect extends beyond the neonatal period, revealing a broader temporal window for microbial modulation of mucosal immune development. These findings reveal a previously unrecognized role for a defined gut commensal bacterium and its molecular products in orchestrating the formation of gut-associated lymphoid tissue and B cell recruitment.

microbiology↗

bioRxiv2025

A novel bioinformatics approach reveals key transcription factors regulating type 1 diabetes-associated transcriptomes

We developed a novel bioinformatics pipeline that reveals key transcription factors (TFs) regulating type 1 diabetes transcriptomes by combining automated Python workflows, DESeq2-based differential expression analysis, motif enrichment, and genome-wide TF abundance profiling, a rare but powerful strategy that deepens our understanding of disease mechanisms. This approach not only uncovers TFs driving pathology but also quantifies TF abundance across multiple genomic loci, enabling rapid and precise monitoring of their occupancy. Analyzing 21 RNA sequencing datasets, including 13 from early-stage T1D patients and 8 matched controls, we identified nearly 6 000 differentially expressed genes; 1 900 met strict significance and fold-change criteria and 211 are previously uncharacterized transcripts that distinguish T1D from healthy samples. Pathway analysis highlighted disruptions in beta-cell signaling, ALK-linked drug responses, neurodegenerative processes, and cytoskeletal organization. Upstream motif analysis revealed enrichment of Myc/Max, AP-1, SP-1, TATA-box, and NF-{kappa}B binding sites in upregulated genes, confirming their central role in the T1D transcriptome. By placing TFs at the core of our discovery platform, this work uncovers novel molecular drivers of T1D and identifies actionable biomarkers and therapeutic targets for personalized treatment.

bioinformatics↗

bioRxiv2025

In Silico Characterization of a Hypothetical Protein from Pseudomonas aeruginosa LESB58: A Structural and Functional Perspective.

BackgroundPseudomonas aeruginosa LESB58 is an omnipresent opportunistic bacteria that causes both acute and persistent infections in immunocompromised people. This bacteria is now on the WHOs red list, meaning that new medicines are desperately needed for treatment. Although the bacterial genome is known, many hypothetical proteins have unidentified activities. Annotating hypothetical proteins can be critical steps toward discovering new druggable targets and treatments. In this work, a hypothetical protein of the Pseudomonas aeruginosa LESB58 strain (accession no. CAW29855.1, 284 amino acids) was chosen for in-depth structural and functional research. Methods & ResultsThe target hypothetical proteins subcellular location and other physicochemical characteristics were estimated to indicate that it is cytoplasmic. Using bioinformatics tools, it was determined that the target protein had the conserved domain of the phenazine biosynthesis protein family. Multiple sequence alignment of the target proteins homologous sequence was produced, which helped to create a phylogenetic tree and identify the target proteins common ancestor. The extended strand was mostly present in the secondary structure produced by PSI-PRED. Using a template protein (PDB ID: 1uok.1.A), a 3D model of the target protein was predicted using the SWISS-MODEL service based on the homology modeling idea. After energy reduction via the YASARA tool, which increases the structures stability the SWISS-MODEL structure was evaluated and validated using multiple tools. The RMSD value of 0.347 [A] was produced by superimposing the target with the template protein using UCSF Chimera, indicating a dependable three-dimensional structure. PrankWeb server anticipated and visualized the modeled structures active site. The target proteins with non-homologous protein against the human proteome and human antitargets are finally predicted by a pipeline builder, suggest that this protein may be a possible therapeutic target. ConclusionBy helping P. aeruginosa evade the hosts immune system and form biofilms that contribute to antibiotic resistance and worsen infections, this protein can boost P. aeruginosa pathogenicity. The studys results, which examine both functional and structural features, might help in the creation of novel antibacterial drug targets and Pseudomonas aeruginosa LSB58 medications.

bioinformatics↗

bioRxiv2025

Dendritic cells activate pyroptosis and effector-triggered apoptosis to restrict Legionella infection

The innate immune system relies on pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) and guard proteins to monitor pathogen disruption of host cell processes. How different immune cell types engage PRR- and guard protein-dependent defenses in response to infection is poorly understood. Here, we show that macrophages and dendritic cells (DCs) respond in distinct ways to bacterial virulence activities. In macrophages, the bacterial pathogen Legionella pneumophila deploys its Dot/Icm type IV secretion system (T4SS) to deliver effector proteins that facilitate its robust intracellular replication. In contrast, T4SS activity triggers rapid DC death that potently restricts Legionella replication within this cell type. Intriguingly, we found that infected DCs exhibit considerable heterogeneity at the single cell level. Initially, a subset of DCs activate caspase-11 and NLRP3 inflammasome-dependent pyroptosis and release IL-1{beta} early during infection. At later timepoints, a separate DC population undergoes apoptosis driven by T4SS effectors that block host protein synthesis, thereby depleting the levels of the pro-survival proteins Mcl-1 and cFLIP. Together, pyroptosis and effector-triggered apoptosis robustly restrict Legionella replication in DCs. Collectively, our work suggests a model where Mcl-1 and cFLIP guard host translation in DCs, and that macrophages and DCs distinctly employ innate immune sensors and guard proteins to mount divergent responses to Legionella infection.

immunology↗

bioRxiv2024

A Comprehensive Pangenome Approach to Exploring the Probiotic Potential of Weissella Confusa

BackgroundFermented foods harbour the bacterium Weissella confusa, which has probiotic properties but can potentially act as an opportunistic pathogen in humans and animals. Using pangenome analysis, our study aimed to improve the classification and identify functional traits of publicly available W. confusa genomes, focusing on evaluating their potential as probiotics. MethodThe genomic sequence of 120 strains of W. confusa was acquired from the NCBI RefSeq database. The downloaded sequences underwent a quality verification and filtering process. Ultimately, the chosen genomes were examined for comparative genomic analysis. We employed Roary to investigate the pangenome of W. confusa. Fishers exact test was utilised to analyse contingency tables, with a significance threshold of p < 0.05 (two-tailed). ResultsOur investigation revealed that the pangenome of W. confusa comprises 1100 core genes, 184 soft-core genes, 1407 shell genes, and 7006 cloud genes. This finding emphasises the "open" aspect of the W. confusa pangenome. The comparison of genomes showed that there were no acquired antibiotic resistance genes. However, the strains had different amounts of prophage regions, CRISPR arrays, and plasmids. Our research identified probiotic marker genes (PMGs), with the majority (78%) found in the core and soft-core genomes of various strains of W. confusa. ConclusionsAn extensive investigation of the W. confusa pangenome has concluded that it could be useful as a probiotic. Additional research is necessary to thoroughly evaluate the potential risks.

bioinformatics↗

bioRxiv2024

Order among chaos: high throughput MYCroplanters can distinguish interacting drivers of host infection in a highly stochastic system

While microbiomes provide diverse benefits for their host, they are notoriously variable in structure and function. As a result, substantial experimental replication and scalability are required to identify the contributions of and interactions between microbiota, the host and the environment. Here, we describe a novel high throughput plant growth system (MYCroplanters) to test how multiple host, microbiota, and pathogen variables predict host health. Using an Arabidopsis-Pseudomonas host-microbiome-pathogen model, we found that host genotype and order of arrival predict competition outcome between strains in the rhizosphere, but pathogen and microbiota dose can overwhelm these effects. Regardless of host or inoculation conditions, final microbial community structure emerged as a consistent predictor of host health. We demonstrate that high-throughput tools like MYCroplanters can isolate interacting drivers of host health. Increasing the scale at which we can screen components of microbiome-mediated host benefits will facilitate building microbiome engineering solutions for medicine and agricultural applications.

ecology↗

bioRxiv2024

GENOME-WIDE IDENTIFICATION, CHARACTERIZATION AND EXPRESSION ANALYSIS OF NA+/H+ EXCHANGER GENE FAMILY IN TWO CORCHORUS SPECIES

Na+/H+ exchangers (NHXs) are secondary ion transporter to exchange H+ and transfer Na+ or K+ across membrane plays crucial role in cellular pH and Na+ and K+ homeostasis in plant. In the present study, we have performed genomewide identification, characterization and comparative analysis of NHXs genes in two cultivated jute species and found seven Co and Cc NHXs in each genome. Subsequently phylogenetic analysis demonstrated that Co and Cc NHXs have three sub-group that correlate with other plant species containing 10-12 transmembrane helices (TMH) and a hydrophilic C-terminal domain in the cytoplasmic region, the TMH compose a hollow cylinder to provide the channel for Na+ and H+ transport. Promoter profiling of both species NHXs genes revealed in enrichment of cis element involved in stress responsiveness reflecting their potential involvement against abiotic stress. Transcriptome data and real time PCR of Co and Cc NHXs gene expression analysis under saline and drought condition showed significant differences, which suggest their potential role in abiotic stress conditions. This is the first comprehensive analysis providing baseline information of Co and Cc NHXs genes in abiotic stress condition which can be used for the development of abiotic stress tolerant jute variety.

bioinformatics↗

bioRxiv2024

Multidimensional analysis of cortical interneuron synaptic features reveals underlying synaptic heterogeneity

Cortical interneurons represent a diverse set of neuronal subtypes characterized in part by their striking degree of synaptic specificity. However, little is known about the extent of synaptic diversity because of the lack of unbiased methods to extract synaptic features among interneuron subtypes. Here, we develop an approach to aggregate image features from fluorescent confocal images of interneuron synapses and their post-synaptic targets, in order to characterize the heterogeneity of synapses at fine scale. We started by training a model that recognizes pre- and post-synaptic compartments and then determines the target of each genetically-identified interneuron synapse in vitro and in vivo. Our model extracts hundreds of spatial and intensity features from each analyzed synapse, constructing a multidimensional data set, consisting of millions of synapses, which allowed us to perform an unsupervised analysis on this dataset, uncovering novel synaptic subgroups. The subgroups were spatially distributed in a highly structured manner that revealed the local underlying topology of the postsynaptic environment. Dendrite-targeting subgroups were clustered onto subdomains of the dendrite along the proximal to distal axis. Soma-targeting subgroups were enriched onto different postsynaptic cell types. We also find that the two main subclasses of interneurons, basket cells and somatostatin interneurons, utilize distinct strategies to enact inhibitory coverage. Thus, our analysis of multidimensional synaptic features establishes a conceptual framework for studying interneuron synaptic diversity.

neuroscience↗

bioRxiv2023

Genome Mining of Salinispora Uncovers a Repertoire of Secondary Metabolites and Carbohydrate-Active Enzymes

Natural products derived from microorganisms are a significant part of the pharmaceutical industrys arsenal today. These efforts have increasingly centred on marine microbes, which have produced a variety of intriguing novel chemicals. Marine-derived strains are likely candidates for natural product discovery since actinomycetes are a significant source of microbially produced natural compounds. The availability of microbial genome sequencing has revealed a number of natural products (NPs) that have not yet been thoroughly investigated. The genome mining potential of the genus Salinispora, which has potential for the production of secondary metabolites of clinical importance, remains unexplored. In this study, we have demonstrated a thorough comprehension of the genetic characteristics, biosynthetic gene clusters (BGCs), and genetic clusters for carbohydrate-active enzymes found in the Salinispora genomes. In our analysis, we have identified 686 BGCs, among which 3.79% are identical to the BGCs that produce ketomemicin B3/ketomemicin B4, salinilactam, lymphostin/neolymphostinol B/lymphostinol/neolymphostin B, benzastatin, and thiolactomycin. We have found 19.5% of the BGCs, which are only present in the genomes of Salinispora and may open the door to the development of novel drugs. We have also found a total of 3604 genes in 62 various categories of the six major carbohydrate-active enzymes. The development of new-generation bioactive compounds that are significant for biotechnology relies heavily on the scientific insights provided by genome mining in this genus.

bioinformatics↗

bioRxiv2023

Host subversion of bacterial metallophore usage drives copper intoxication

Microorganisms can acquire metal ions in metal-limited environments using small molecules called metallophores. While metals and their importers are essential, metals can also be toxic, and metallophores have limited ability to discriminate metals. The impact of the metallophore-mediated non-cognate metal uptake on bacterial metal homeostasis and pathogenesis remains to be defined. The globally significant pathogen Staphylococcus aureus uses the Cnt system to secrete the metallophore staphylopine in zinc-limited host niches. Here, we show that staphylopine and the Cnt system facilitate bacterial copper uptake, potentiating the need for copper detoxification. During in vivo infection, staphylopine usage increased S. aureus susceptibility to host-mediated copper stress, indicating that the innate immune response can harness the antimicrobial potential of altered elemental abundances in host niches. Collectively, these observations show that while the broad-spectrum metal-chelating properties of metallophores can be advantageous, the host can exploit these properties to drive metal intoxication and mediate antibacterial control. IMPORTANCEDuring infection bacteria must overcome the dual threats of metal starvation and intoxication. This work reveals that the zinc-withholding response of the host sensitizes Staphylococcus aureus to copper intoxication. In response to zinc starvation S. aureus utilizes the metallophore staphylopine. The current work revealed that the host can leverage the promiscuity of staphylopine to intoxicate S. aureus during infection. Significantly, staphylopine-like metallophores are produced by a wide range of pathogens, suggesting that this is a conserved weakness that the host can leverage to toxify invaders with copper. Moreover, it challenges the assumption that the broad-spectrum metal binding of metallophores is inherently beneficial to bacteria.

microbiology↗

bioRxiv2022

Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B

Much of our current understanding of how small-molecule ligands interact with proteins stems from X-ray crystal structures determined at cryogenic (cryo) temperature. For proteins alone, room-temperature (RT) crystallography can reveal previously hidden, biologically relevant alternate conformations. However, less is understood about how RT crystallography may impact the conformational landscapes of protein-ligand complexes. Previously we showed that small-molecule fragments cluster in putative allosteric sites using a cryo crystallographic screen of the therapeutic target PTP1B (Keedy*, Hill*, 2018). Here we have performed two RT crystallographic screens of PTP1B using many of the same fragments, representing the largest RT crystallographic screens of a diverse library of ligands to date, and enabling a direct interrogation of the effect of data collection temperature on protein-ligand interactions. We show that at RT, fewer ligands bind, and often more weakly -- but with a variety of temperature-dependent differences, including unique binding poses, changes in solvation, new binding sites, and distinct protein allosteric conformational responses. Overall, this work suggests that the vast body of existing cryogenic-temperature protein-ligand structures may provide an incomplete picture, and highlights the potential of RT crystallography to help complete this picture by revealing distinct conformational modes of protein-ligand systems. Our results may inspire future use of RT crystallography to interrogate the roles of protein-ligand conformational ensembles in biological function.

biophysics↗

bioRxiv2022

Tactile Stimulation Improves Cognition, Motor, and Anxiety-Like Behaviours and Attenuates the AD Pathology in Adult APP NL-G-F/NL-G-F mice

Alzheimers Disease (AD) is one of the largest health crises in the world. There are, however, limited but expensive pharmaceutical interventions to treat AD and most of the treatment options are not for cure or prevention, but to slow down the progression of the disease. The aim of this study was to examine the effect of tactile stimulation on AD-like symptoms and pathology in APP NL-G-F/NL-G-F mice, a mouse model of AD. The results show that tactile stimulation improves the AD-like symptoms on tests of cognition, motor, and anxiety-like behaviours and these improvements are associated with reduced AD pathology in APP mice.

neuroscience↗

bioRxiv2022

Early Tactile Stimulation Influences the Development of Alzheimer Disease in Gestationally Stressed APPNL-G-F/ NL-G-F Adult mice

Alzheimer Disease (AD) is associated with cerebral plaques and tangles, reduced synapse number, and shrinkage in several brain areas and these morphological effects are associated with the onset of compromised cognitive, motor, and anxiety-like behaviours. The focus of this study was to examine the effect of neonatal tactile stimulation on AD-like behavioural and neurological symptoms on APP NL-G-F/NL-G-F mice, a mouse model of AD. Our findings indicate that neonatal tactile stimulation improves cognition, motor skills, and anxiety-like symptoms in both gestationally stressed and non-stressed adult APP mice and that these alterations are associated with reduced A{beta} plaque formation. Thus, tactile stimulation appears to be a promising non-invasive preventative strategy for slowing the onset of dementia in aging animals.

neuroscience↗

bioRxiv2021

Nerve-mediated amputation-induced stem cell activation primes distant appendages for future regeneration events in axolotl

Many species regenerate lost body parts following amputation. Most limb regeneration research has focused on the immediate injury site. Meanwhile, body-wide injury responses remain largely unexplored but may be critical for regeneration. Here, we discovered a role for the sympathetic nervous system in stimulating a body-wide stem cell activation response to amputation that drives enhanced limb regeneration in axolotls. This response is mediated by adrenergic signaling, which coordinates distant cellular activation responses via the 2A-adrenergic receptor, and local regeneration responses via {beta}-adrenergic receptors. Both 2A- and {beta}-adrenergic signaling act upstream of mTOR signaling. Notably, systemically-activated axolotls regenerate limbs faster than naive animals, suggesting a potential selective advantage in environments where injury from cannibalism or predation is common. This work challenges the predominant view that cellular responses underlying regeneration are confined to the injury site and argues instead for body-wide cellular priming as a foundational step that enables localized tissue regrowth.

developmental biology↗

bioRxiv2021

Oxygen depletion and nitric oxide stimulate type IV MSHA pilus retraction in Vibrio cholerae via activation of the phosphodiesterase CdpA

Bacteria use surface appendages called type IV pili to perform diverse activities including DNA uptake, twitching motility, and attachment to surfaces. Dynamic extension and retraction of pili is often required for these activities, but the stimuli that regulate these dynamics remain poorly characterized. To study this question, we use the bacterial pathogen Vibrio cholerae, which uses mannose-sensitive hemagglutinin (MSHA) pili to attach to surfaces in aquatic environments as the first step in biofilm formation. Here, we find that V. cholerae cells retract MSHA pili and detach from a surface in microaerobic conditions. This response is dependent on the phosphodiesterase CdpA, which decreases intracellular levels of cyclic-di-GMP (c-di-GMP) under microaerobic conditions to induce MSHA pilus retraction. CdpA contains a putative NO-sensing NosP domain, and we demonstrate that nitric oxide (NO) is necessary and sufficient to stimulate CdpA-dependent detachment. Thus, we hypothesize that microaerobic conditions result in endogenous production of NO (or an NO-like molecule) in V. cholerae. Together, these results describe a regulatory pathway that allows V. cholerae to rapidly abort biofilm formation. More broadly, these results show how environmental cues can be integrated into the complex regulatory pathways that control pilus dynamic activity and attachment in bacterial species.

microbiology↗