Biology subjects

Hossain, S. S.

Publications and source records attributed to Hossain, S. S..

5 recordsLinked to original sources

bioRxiv2025

Intrinsically disordered regions facilitate Msn2 target search to drive promoter selectivity

Transcription factors (TFs) regulate gene expression by binding specific DNA motifs, yet only a fraction of putative sites is occupied in vivo. Intrinsically disordered regions (IDRs) have emerged as key contributors to promoter selectivity, but the underlying mechanisms remain incompletely understood. Here, we use single-molecule optical tweezers to dissect how IDRs influence DNA binding by Msn2, a yeast stress-response regulator. We show that IDRs facilitate initial non-specific association with DNA and promote one-dimensional diffusion toward target motifs, supported by charge-mediated interactions. Remarkably, the IDR-dependent search mechanism displays sequence sensitivity, with promoter-derived sequences enhancing both initial binding and sliding rates, demonstrating that Msn2-DNA interactions alone are sufficient to confer promoter selectivity in the absence of chromatin or cofactors. These findings provide direct mechanistic evidence for how IDRs tune transcription factor search dynamics and expand sequence recognition beyond canonical motifs, supporting a mechanism for promoter selectivity in complex genomic contexts.

biophysics↗

bioRxiv2021

A novel method for improving the accuracy of MR-derived patient-specific vascular models using X-ray angiography

MR imaging is a noninvasive imaging modality that is commonly used during clinical follow up and has been widely utilized to reconstruct realistic 3D vascular models for patient-specific analysis. In a recent work, we utilized patient-specific hemodynamic analysis of the circle of Willis to noninvasively assess stroke risk in pediatric Moyamoya disease (MMD)--a progressive steno-occlusive cerebrovascular disease that leads to recurrent stroke. The objective was to identify vascular regions with critically high wall shear rate (WSR), signifying elevated stroke risk. However, sources of error including insufficient resolution of MR images can negatively impact vascular model accuracy, especially in areas of severe pathological narrowing, and thus diminish clinical relevance of simulation results, as local hemodynamics are sensitive to vessel geometry. We have developed a novel method to improve the accuracy of MR-derived 3D vascular models utilizing 2D X-ray angiography (XA), which is considered the gold standard for clinically assessing vessel caliber. In this workflow, "virtual angiographies" (VA) of 3D MR-derived vascular models are conducted, producing 2D projections that are compared to corresponding XA images guiding the local adjustment of modeled vessels. This VA-comparison-adjustment loop is iterated until the two agree, as confirmed by an expert neuroradiologist. Using this method, we generated models of the circle of Willis of two patients with a history of unilateral stroke. Blood flow simulations were performed using a Navier-Stokes solver within an isogeoemtric analysis framework and WSR distributions were quantified. Results for one patient show as much as 45% underestimation of local WSR in the stenotic left anterior cerebral artery (LACA) and up to a 60% underestimation in the right anterior cerebral artery when using the initial MR-derived model compared to the XA-adjusted model, emphasizing the need for verifying improved accuracy of the adjusted model. To that end, vessel cross-sectional areas of the pre- and post-adjustment models were compared to those seen in 3D CTA images of the same patient. CTA has superior resolution and signal to noise ratio compared to MR imaging but is not commonly used in clinic due to radiation exposure concerns, especially in pediatric patients. While the vessels in the initial model had normalized root mean squared deviations (NRMSDs) ranging from 26% to 182% and 31% to 69% in two patients with respect to CTA, the adjusted vessel NRMSDs were comparatively smaller (32% to 53% and 11% to 42%). In the mildly stenotic LACA of patient 1, the NRMSDs for the pre- and post-adjusted models were 49% and 32%, respectively. These findings suggest that our XA-based adjustment method can considerably improve the accuracy of vascular models, and thus, stroke-risk prediction. An accurate individualized assessment of stroke risk would be of substantial clinical benefit because it would help guide the timing of preventative surgical interventions in pediatric MMD patients.

bioengineering↗

bioRxiv2021

Commensal Pseudomonas fluorescens protect Arabidopsis from closely-related Pseudomonas pathogens in a colonization-dependent manner

Plants form commensal associations with soil microorganisms, creating a root microbiome that provides benefits to the host including protection against pathogens. While bacteria can inhibit pathogens through production of antimicrobial compounds in vitro, it is largely unknown how microbiota contribute to pathogen protection in planta. We developed a gnotobiotic model system consisting of Arabidopsis thaliana, and an opportunistic pathogen Pseudomonas sp. N2C3, to identify mechanisms that determine the outcome of plant-pathogen-microbiome interactions in the rhizosphere. We screened 25 phylogenetically diverse Pseudomonas strains for their ability to protect against N2C3 and found that commensal strains closely related to N2C3 were more likely to protect against pathogenesis. We used a comparative genomics approach to identify unique genes in the protective strains that revealed no genes that correlate with protection, suggesting that variable regulation of components of the core Pseudomonas genome may contribute to pathogen protection. We found that commensal colonization level was highly predictive of protection and so tested deletions in genes previously shown to be required for Arabidopsis rhizosphere colonization. We identified a response regulator colR that is required for Pseudomonas protection from N2C3 and fitness in competition with N2C3 indicating that competitive exclusion may contribute to pathogen protection. We found that Pseudomonas WCS365 also protects against the agricultural pathogen Pseudomonas fuscovaginae SE-1, the causal agent of bacterial sheath brown rot of rice. This work establishes a gnotobiotic model to uncover mechanisms by which members of the microbiome can protect hosts from pathogens and informs our understanding of the use of beneficial strains for microbiome engineering in dysbiotic soil systems.

microbiology↗

bioRxiv2018

A genome-wide screen identifies genes in rhizosphere-associated Pseudomonas required to evade plant defenses

Pseudomonas fluorescens and related plant root- (\"rhizosphere\") associated species contribute to plant health by modulating defenses and facilitating nutrient uptake. To identify bacterial fitness determinants in the rhizosphere of the model plant Arabidopsis thaliana, we performed a Tn-Seq screen using the biocontrol and growth-promoting strain Pseudomonas sp. WCS365. The screen, which was performed in parallel on wild-type and an immunocompromised Arabidopsis, identified 231 genes that positively affect fitness in the rhizosphere of wild-type plants. A subset of these genes negatively affect fitness in the rhizosphere of immunocompromised plants. We postulated that these genes might be involved in avoiding plant defenses and verified 7 Pseudomonas sp. WCS365 candidate genes by generating clean deletions. We found that two of these deletion strains, {Delta}morA (encodes a putative diguanylate cyclase/phosphodiesterase) and {Delta}spuC (encodes a putrescine aminotransferase) formed enhanced biofilms and inhibited plant growth. Inhibition of plant growth by {Delta}spuC and {Delta}morA was the result of pattern triggered immunity (PTI) as measured by induction of an Arabidopsis PTI reporter and FLS2/BAK1-dependent inhibition of plant growth. We found that MorA acts as a phosphodiesterase to inhibit biofilm formation suggesting a possible role in biofilm dispersal. We found that both putrescine and its precursor arginine promote biofilm formation that is enhanced in the {Delta}spuC mutant, which cannot break down putrescine suggesting that putrescine might serve as a signaling molecule in the rhizosphere. Collectively, this work identified novel bacterial factors required to evade plant defenses in the rhizosphere.\n\nImportanceWhile rhizosphere bacteria hold the potential to improve plant health and fitness, little is known about the bacterial genes required to evade host immunity. Using a model system consisting of Arabidopsis and a beneficial Pseudomonas sp. isolate, we identified bacterial genes required for both rhizosphere fitness and for evading host immune responses. This work advances our understanding of how evasion of host defenses contributes to survival in the rhizosphere.

microbiology↗

bioRxiv2018

Convergent gain and loss of genomic islands drives lifestyle changes in plant-associated bacteria

Host-associated bacteria can have both beneficial and detrimental effects on host health. While some of the molecular mechanisms that determine these outcomes are known, little is known about the evolutionary histories of pathogenic or mutualistic lifestyles. Using the model plant Arabidopsis, we found that closely related strains within the Pseudomonas fluorescens species complex promote plant growth and occasionally cause disease. To elucidate the genetic basis of the transition between commensalism and pathogenesis, we developed a computational pipeline and identified genomic islands that correlate with outcomes for plant health. One island containing genes for lipopeptide biosynthesis and quorum sensing is required for pathogenesis. Conservation of the quorum sensing machinery in this island allows pathogenic strains to eavesdrop on quorum signals in the environment and coordinate pathogenic behavior. We found that genomic loci associated with both pathogenic and commensal lifestyles were convergently gained and lost in multiple lineages through homologous recombination, possibly constituting an early step in the differentiation of pathogenic and commensal lifestyles. Collectively this work provides novel insights into the evolution of commensal and pathogenic lifestyles within a single clade of host-associated bacteria.

microbiology↗