Biology subjects

Maity, T.

Publications and source records attributed to Maity, T..

6 recordsLinked to original sources

bioRxiv2026

Polystyrene Microplastics Accelerate Antibiotic Resistance Evolution and Exacerbate Pathogenicity in Acinetobacter Baumannii

Microplastics are pervasive environmental contaminants and are increasingly detected in contexts relevant to human health, yet their effects on antimicrobial resistance, host-pathogen interactions, and infection outcomes remain poorly understood. Here, we show that exposure to polystyrene microplastics alters both antibiotic resistance evolution and pathogenic behavior in Acinetobacter baumannii, a leading cause of multidrug-resistant hospital-acquired infections. Using experimental evolution under antibiotic selection, we demonstrate that microplastic exposure accelerates resistance emergence across multiple antibiotic classes. Although microplastic exposure did not uniformly enhance biofilm formation, it modestly impaired macrophage-mediated bacterial clearance, suggesting broader effects on bacterial adaptation and host interaction. In vivo, microplastic-associated infection resulted in more severe disease, characterized by increased lung tissue damage and reduced survival in a murine model of A. baumannii pneumonia. Together, these findings identify microplastics as ecological modifiers of bacterial adaptation, linking widespread plastic pollution to enhanced antimicrobial resistance and worsened infectious disease outcomes.

microbiology↗

bioRxiv2026

DISRUPTION OF A DNA REPAIR PROTEIN PROMOTES ANTIBIOTIC RESISTANCE IN ACINETOBACTER BAUMANNII

Acinetobacter baumannii is a high priority Gram negative opportunistic pathogen known for its high rates of multidrug resistance (MDR). Minocycline (MIN), a tetracycline class antibiotic, is one of the most effective antibiotics for treating A. baumannii infections in patients. Unfortunately, MIN resistance is spreading internationally and has begun to emerge in the United States. While efflux pumps are correlated with MIN resistant A. baumannii, clinical data suggests alternative mechanisms of MIN resistance. To explore the genetic basis for MIN resistance in A. baumannii we employed a machine learning model to predict genetic resistance correlates from clinical isolates. Mutations in ruvB, a DNA repair protein, were strongly correlated with MIN resistant clinical strains of A. baumannii .Consistent with the prediction, tn26 insertion in ruvB in A. baumannii strain AB5075, and deletion of ruvB in strain ATCC 19606, increased MIN minimum inhibitory concentrations to a level that exceeds the MIN resistance breakpoint. RuvB complexes with RuvA and RuvC to resolve Holliday junctions during recombination. However, only ruvB mutants showed the resistance phenotype; neither ruvA nor ruvC mutants were MIN resistant, suggesting loss of the activity of the complex was not the basis for resistance. We observed ruvB mutants produced increased biomass during planktonic growth relative to the other two ruv mutants. Upon examination, the ruvB::tn26 mutant had a 451% increase in biomass and 360% thicker biofilms relative to wildtype. We determined the disruption of ruvB lead to thicker biofilms and enriched in extracellular DNA (eDNA), and DNase I treatment collapsed the enhanced biofilm phenotype and markedly reduced tetracycline class MICs. FLAG-RuvA accumulated within the biofilm matrix in the absence of RuvB, supporting a model in which RuvA contributes to stabilization of eDNA-rich structures. In a murine pneumonia model, ruvB disruption did not significantly alter survival or pulmonary burden in untreated infection but reduced bacterial dissemination and increased minocycline resistance. Together, these findings reveal an unexpected connection between Holliday junction processing, eDNA-rich biofilm architecture, and antibiotic resistance in A. baumannii.

microbiology↗

bioRxiv2026

A Clinically Silent Resistance Phenotype That Promotes Acinetobacter baumannii Survival During Colistin Therapy

Acinetobacter baumannii is a major cause of multidrug-resistant nosocomial infections, particularly ventilator-associated pneumonia, for which therapeutic options are increasingly limited. Colistin, a polymyxin antibiotic, is a drug of last resort for A. baumannii, boasting high susceptibility rates. Yet, despite relatively low rates of breakpoint-defined colistin resistance, clinical outcomes are highly variable, and the bacterial strategies that enable survival during colistin therapy remain poorly understood. Here, we integrate supervised machine-learning-guided genomic prioritization with functional, physiological, and in vivo analyses to interrogate the genetic basis of colistin response in A. baumannii. Machine-learning analysis of clinical isolates identified candidate loci associated with colistin survival, many of which did not alter minimum inhibitory concentration (MIC) when disrupted. Instead, growth-dynamic assays uncovered a subset of mutants capable of maintaining fitness upon inhibitory colistin exposure despite classification as susceptible via standardized antibiotic susceptibility testing. We define this phenotype as clinically silent resistance (CSR), a genetically encoded, MIC-independent survival state. Using a murine pneumonia model, we further demonstrate that CSR mutants thrive during colistin therapy in vivo. Together, these findings reveal a hidden layer of colistin survival that is not captured by standard susceptibility testing and highlight fundamental limitations of breakpoint-centric paradigms for predicting treatment outcomes in A. baumannii.

microbiology↗

bioRxiv2025

siRNA complexation with Galactose-Functionalized Dendrimer: PAMAM vs PETIM

siRNA-based therapies hold promise for treating various diseases, but efficient and targeted delivery remains challenging. This study explored the potential of galactose-functionalized poly(amidoamine) (Gal-PAMAM) and poly(propyl ether amine) (Gal-PETIM) dendrimers as siRNA carriers using all-atom molecular dynamics simulations. This study revealed distinct complexation behavior for both the system in physiological (pH [~] 7) and high (pH [~] 10) environments. Electrostatic interactions dominated complexation, with PMF profiles revealing stronger binding affinity for Gal-PAMAM/siRNA at pH 7. siRNA displayed lower flexibility at pH 7 for both complexes, indicating enhanced stability. These findings suggest that Gal-PAMAM dendrimers at physiological pH hold promise for efficient siRNA delivery due to their superior complex stability and interaction strength. However, in polar solvents, Gal-PETIM exhibits hydrophobic behavior, enabling rapid delivery.

biophysics↗

bioRxiv2020

Global proteome and phosphoproteome alterations in third generation EGFR TKI resistance reveal drug targets to circumvent resistance

Lung cancer is the leading cause of cancer mortality worldwide. The treatment of lung cancer patients harboring mutant EGFR with orally administered EGFR TKIs has been a paradigm shift. Osimertinib and rociletinib are 3rd generation irreversible EGFR TKIs targeting the EGFR T790M mutation. Osimertinib is the current standard care for patients with EGFR mutations due to increased efficacy, lower side effects, and enhanced brain penetrance. Unfortunately, all patients develop resistance. Genomic approaches have primarily been used to interrogate resistance mechanisms. Here, we have characterized the proteome and phosphoproteome of a series of isogenic EGFR mutant lung adenocarcinoma cell lines that are either sensitive or resistant to these drugs. To our knowledge, this is the most comprehensive proteomic dataset resource to date to investigate 3rd generation EGFR TKI resistance in lung adenocarcinoma. We have interrogated this unbiased global quantitative mass spectrometry dataset to uncover alterations in signaling pathways, reveal a proteomic signature of epithelial mesenchymal transition (EMT) and identify kinases and phosphatases with altered expression and phosphorylation in TKI resistant cells. Decreased tyrosine phosphorylation of key sites in the phosphatase SHP2 suggests its inhibition resulting in inhibition of RAS/MAPK and activation of PI3K/AKT pathways. Furthermore, we performed anticorrelation analyses of this phosphoproteomic dataset with the published drug-induced P100 phosphoproteomic datasets from the Library of Integrated Network-Based Cellular Signatures (LINCS) program to predict drugs with the potential to overcome EGFR TKI resistance. We identified dactolisib, a PI3K/mTOR inhibitor, which in combination with osimertinib overcomes resistance both in vitro and in vivo.One Sentence Summary Global quantitative proteome and phosphoproteome analyses to examine altered signaling pathways in isogenic 3rd generation EGFR TKI sensitive and resistant cells.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗

bioRxiv2018

The TRIM-NHL protein NHL-2 is a Novel Co-Factor of the CSR-1 and HRDE-1 22G-RNA Pathways

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.

genetics↗