Biology subjects

Banerji, D.

Publications and source records attributed to Banerji, D..

3 recordsLinked to original sources

bioRxiv2020

Sexual conflict drives micro- and macroevolution of sexual dimorphism in immunity

BackgroundSexual selection can have major effects on mating rates and sex-specific costs of mating and may thereby influence sex-differences in immunity as well as associated host-pathogen dynamics. Yet, experimental evidence linking the mating system to evolved sexual dimorphism in immunity are scarce and the direct effects of mating rate on immunity are not well established. Here, we use transcriptomic analyses, experimental evolution and phylogenetic comparative methods to study the association between the mating system and sexual dimorphism in immunity in seed beetles, where mating causes internal injuries in females. ResultsWe demonstrate that female phenoloxidase (PO) activity, involved in wound healing and defence against parasitic infections, is elevated relative to males. This difference is accompanied by concomitant sex-differences in the expression of genes in the pro-phenoloxidase activating cascade. We document substantial phenotypic plasticity in female PO activity in response to mating and show that experimental evolution under enforced monogamy (resulting in low remating rates and sexual conflict relative to natural polygamy) rapidly decreases female (but not male) PO activity. Moreover, monogamous females have evolved increased tolerance to bacterial infection unrelated to mating, implying that female responses to costly mating may trade off with other aspects of immune defence, an hypothesis which broadly accords with the documented sex differences in gene expression. Finally, female (but not male) PO activity shows correlated evolution with the perceived harmfulness of male genitalia across 12 species of seed beetles, suggesting that sexual conflict has a significant influence on sexual dimorphisms in immunity in this group of insects. ConclusionsOur study provides insights into the links between sexual conflict and sexual dimorphism in immunity at the molecular and phenotypic level and suggests that selection pressures moulded by mating interactions can lead to a sex-specific mosaic of immune responses with important implications for host-pathogen dynamics in sexually reproducing organisms.

evolutionary biology↗

bioRxiv2019

Serological and metagenomic interrogation of cerebrospinal fluid implicates enteroviruses in pediatric acute flaccid myelitis

BackgroundSince 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.\n\nMethodsWe interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.\n\nResultsThe most significantly enriched viral family by VirScan of CSF in AFM versus OND controls was Picornaviridae (mean rpK 11,266 versus mean rpK 950, p-adjusted < 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). Enriched Picornaviridae peptides belonged almost entirely to the genus Enterovirus. The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value < 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.\n\nConclusionDespite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM.

microbiology↗

bioRxiv2017

Metagenomics for chronic meningitis: clarifying interpretation and diagnosis

ImportanceIdentifying infectious causes of subacute and chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed.\n\nObjectiveTo present a case series of patients with diagnostically challenging subacute and chronic meningitis in whom metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF), supported by a statistical framework generated from mNGS sequencing of non-infectious patients and environmental controls, identified a pathogen.\n\nDesignCase series. Using mNGS data from the CSF of 94 non-infectious neuroinflammatory cases and 24 water and reagent controls, we developed and implemented a weighted scoring metric based on z-scores at the species and genus level for both nucleotide and protein databases to prioritize and rank mNGS results. We performed mNGS on total RNA extracted from CSF of patients with subacute or chronic meningitis and highlight seven cases representing a diverse array of pathogens.\n\nSettingA multi-center study of mNGS pathogen discovery in patients with suspected neuroinflammatory conditions.\n\nParticipantsPatients with diagnostically challenging subacute or chronic meningitis enrolled in a research study of mNGS performed on CSF.\n\nInterventionmNGS was performed on total RNA extracted from CSF (0.25-0.5 mL). A weighted z-score was used to filter out environmental contaminants and facilitate efficient data triage and analysis.\n\nMain Outcomes1) Pathogens identified by mNGS and 2) ability of a statistical model to prioritize, rank, and simplify mNGS results.\n\nResultsmNGS identified parasitic worms, fungi and viruses in seven subjects: Taenia solium (n=2), Cryptococcus neoformans, human immunodeficiency virus-1, Aspergillus oryzae, Histoplasma capsulatum, and Candida dubliniensis. Evaluating mNGS data with a weighted z-score based scoring algorithm effectively separated bona fide pathogen sequences from spurious environmental sequences.\n\nConclusions and RelevancemNGS of CSF identified a diversity of microbial pathogens in patients with diagnostically challenging subacute or chronic meningitis, including a case of subarachnoid neurocysticercosis that defied diagnosis for one year, the first case of CNS vasculitis caused by Aspergillus oryzae, and the fourth reported case of Candida dubliniensis meningitis. Filtering metagenomic data with a scoring algorithm greatly clarified data interpretation and highlights the difficulties attributing biological significance to organisms that may be present in control samples used for metagenomic sequencing studies.\n\nKey PointsQuestion: How can metagenomic next-generation sequencing of cerebrospinal fluid be leveraged to aid in the diagnosis of patients with subacute or chronic meningitis?\n\nFindings: Metagenomic next-generation sequencing identified parasitic worms, fungi and viruses in a case series of seven subjects. A database of water-only and healthy patient controls enabled application of a z-score based scoring algorithm to effectively separate bona fide pathogen sequences from spurious environmental sequences.\n\nMeaning: Our scoring algorithm greatly simplified data interpretation in a series of patients with a wide range of challenging infectious causes of subacute or chronic meningitis identified by metagenomic next-generation sequencing.

microbiology↗