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Halder, B.

Publications and source records attributed to Halder, B..

3 recordsLinked to original sources

Colistin resistance-mediated lipopolysaccharide modification in Klebsiella pneumoniae modulates host inflammatory response

Resistance to the polymyxin antimicrobial colistin in Gram-negative bacteria is associated with a modification of the immunogenic lipid A moiety of the lipopolysaccharide (LPS). Chromosomal and plasmid-borne colistin resistance results in the addition of L-Ara4N and pEtN groups to lipopolysaccharide (LPS), respectively. Here, using THP-1 cells, we studied the impact of different LPS modifications of Klebsiella pneumoniae in stimulating host immune response. K. pneumoniae clinical isolates were screened for colistin resistance using broth microdilution (BMD) and the MALDIxin test. LPS was extracted from colistin-resistant isolates and used to stimulate differentiated THP-1 cells. Luminex cytokine assay measured the immune induction via a panel of proinflammatory cytokines. Out of a collection of 72 clinical K. pneumoniae, eight (11.1%) exhibited phenotypic colistin resistance with a minimum inhibitory concentration (MIC) of 8 to 64 mg/L. In total, five isolates possessed genes associated with polymyxin resistance; three isolates had a mutation in the pmrB gene, and two were mcr-8.1 positive. MALDIxin demonstrated that all eight phenotypic colistin-resistant isolates elaborated peaks at m/z 1,955 and m/z 2,193, indicating an L-Ara4N group of LPS modification. For two mcr-8.1 positive isolates, LPS had a pEtN group. The LPS modification positively correlated with colistin MIC (correlation coefficient, r= 0.6 and R2= 0.4). Compared to the native structure, LPS modification was associated with greater production of IL-1{beta}, IL-6, and CXCL-8 (p<0.001). The pEtN-conjugated LPS triggered a significantly greater production of TNF-, IL-6, and CXCL-8 compared to L-Ara4N (p<0.05). This study reveals that the colistin MIC value can significantly predict lipid A modification in clinical K. pneumoniae, and differences in resistance-mediated lipid A modification result in variation in the immunological response. This study highlights the potential of dynamic host-pathogen interaction in the context of colistin resistance.

microbiology↗

To jump or not to jump: Comparing effects of phenotypic plasticity on the visual responses and escape behavior of locusts and grasshoppers

Locusts exhibit remarkable phenotypic plasticity changing their appearance and behavior from solitary grasshoppers to gregarious locusts when population density increases. These changes include morphological differences in the size and shape of brain regions, but little is known about plasticity within individual neurons and alterations in behavior not directly related to aggregation or swarming. We examined looming escape behavior and the properties of a well-studied collision-detection neuron in gregarious and solitarious animals of three closely related species, the desert locust (Schistocerca gregaria), the Central American locust (S. piceifrons) and the American bird grasshopper (S. americana). For this neuron, the lobula giant movement detector (LGMD), we examined dendritic morphology, membrane properties, gene expression, and looming responses. Gregarious animals reliably jumped in response to looming stimuli, but surprisingly solitarious desert locusts did not produce escape jumps. These solitarious animals also had smaller LGMD dendrites. This is the first study done on three different species of grasshoppers to observe the effects of phenotypic plasticity on the jump escape behavior, physiology and transcriptomics of these animals. Surprisingly, there were little differences in these properties between the two phases except for behavior. For all the three species, gregarious animals jumped more than solitarious animals, but no significant differences were found between the two phases of animals in the electrophysiological and transcriptomics studies. Our results suggest that phase change impacts mainly the motor system and that the physiological properties of motor neurons need to be characterized to understand fully the variation in jump escape behavior across phases. New & Noteworthy (74 words): Swarming is observed in some grasshopper species, called locusts. We compared jump escape behavior between gregarious and solitarious grasshoppers and locusts, as well as LGMD responses to looming stimuli, and analyzed the morphological differences in this neuron. This study provides insights into the effects of phase change on the visual system of locusts and grasshoppers as it relates to looming-evoked jump escape behavior. In this context, our results suggest that phenotypic plasticity mainly impacts the motor system.

neuroscience↗

ER tethering and active transport govern condensate diffusion during hyperosmotic stress

BackgroundHyperosmotic shock and the resulting cell volume compression are commonly experienced by organs such as the kidneys, causing rapid formation of hyperosmotic phase separation (HOPS) condensates in the cytoplasm and nucleoplasm. Although the tight relationship between hyperosmotic shock and condensation has been characterized, the dynamics of biomolecular condensates in hyperosmotically compressed cells and their regulatory mechanisms remain largely unknown. ResultsWe used live-cell single-particle tracking (SPT) across different time scales to systematically characterize the dynamics of HOPS condensates formed by model protein mRNA decapping enzyme 1A (DCP1A). We found that HOPS condensates predominantly exhibited sub-diffusion rather than free diffusion, whereas some ([~]2%) exhibited short super-diffusion. Using tools measuring spatial accessibility inside cells and fluorescence labels for specific cellular organelles, we further revealed the origins of sub-diffusion and super-diffusion as endoplasmic reticulum (ER) attachment and coupling to microtubule-dependent active transport, respectively. Further, we reconstructed an accessibility map of the hyperosmotically compressed cell from trajectories of genetically encoded multimeric nanoparticles (GEMs), revealing that the cytoplasm of a compressed cell remains highly accessible without significant local corrals. ConclusionsIn contrast to prior portrayals of the cytosolic space as static and constrained, our data suggest that the cytosol of a hyperosmotically compressed cell remains dynamic and accessible. Meanwhile, hyperosmotic and potentially other condensates can be spatially organized through docking to membrane structures, with intermittent episodes of long-range transport. These insights broaden our understanding of the physical environment within cells under hyperosmotic shock and provide a model for spatiotemporal organization of condensates via docking or coupling to existing cellular structures and processes.

biophysics↗