Biology subjects

Bordenstein, S.

Publications and source records attributed to Bordenstein, S..

3 recordsLinked to original sources

bioRxiv2025

Wolbachia and its pWCP plasmid show differential dynamics during the development of Culex mosquitoes

Mosquitoes are major vectors of pathogens such as arboviruses and parasites, causing significant health impacts each year. Wolbachia, an intracellular bacterium widely distributed among arthropods, represents a promising vector control solution. This bacterium can reduce the transmission of dengue, Zika and chikungunya arboviruses and manipulate the reproduction of its host through its prophage WO. Although research on the Wolbachia mobilome primarily focuses on WO and the phenotypes it induces, the function of Wolbachia plasmid pWCP, recently discovered and reported to be strikingly conserved worldwide, remains unknown. In this study, we analyzed the presence and abundance of pWCP as well as Wolbachia in two different species of Culex mosquitoes, one of the most widespread genera in the world and a vector of numerous diseases. We compared relative densities of the bacterium and its mobile genetic element in Culex pipiens molestus and Culex quinquefasciatus, a facultatively autogenous and a anautogenous species, respectively, throughout their development from larval stage L1 to adult individual specimen using quantitative PCR. Our results suggest that 2-5 copies of pWCP occur in Wolbachia cells on average, and the plasmid co-replicates with Wolbachia cells. Moreover, Wolbachia and pWCP exhibit differential levels of abundance at specific development stages throughout the mosquitos life cycle in each species. These findings indicate important, and likely beneficial, roles for the plasmid in the bacteriums biology in different mosquito species as well as complex interaction dynamics between Wolbachia and its host during its life cycle. ImportanceMosquitoes of the Culex genus are critical vectors for numerous diseases, causing significant public health concerns. The intracellular bacterium Wolbachia has emerged as a promising vector control solution due to its ability to interfere with pathogen transmission and manipulate mosquito reproduction. However, unlike the extensively studied WO phage, the biological significance and function of Wolbachias pWCP plasmid, a recently discovered and strikingly conserved mobile genetic element in Culex species, remains unknown. This study investigates the developmental dynamics of pWCP and Wolbachia in two Culex mosquito species, Culex pipiens molestus and Culex quinquefasciatus across their life cycle. In general, the abundance levels of Wolbachia and the plasmid were found to vary across life stages and differ between the two species. However, a relatively small number of pWCP copies were observed per Wolbachia cell, together with a co-replication of the plasmid with the bacterium for most developmental stages. Altogether, these findings suggest a likely beneficial and non-parasitic role for pWCP in Wolbachias biology, that may contribute to the intricate interactions between the bacterium and its mosquito hosts.

microbiology↗

bioRxiv2023

Low Gut Microbial Diversity Augments Estrogen-driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease

Although profibrotic cytokines such as IL-17A and TGF-{beta}1 have been implicated in interstitial lung disease (ILD) pathogenesis, interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as phosphorylation of STAT3, have not been defined. Here we show by chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells that regions within the STAT3 locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung. Genetic absence of ESR1 or ovariectomy in mice significantly increased pSTAT3 and IL-17A expression in pulmonary CD4+ T cells, which was reduced after repletion of female hormones. Remarkably, there was no significant reduction in lung fibrosis under either condition, suggesting that factors outside of ovarian hormones also contribute. Assessment of lung fibrosis among menstruating females in different rearing environments revealed that environments favoring gut dysbiosis augment fibrosis. Furthermore, hormone repletion following ovariectomy further augmented lung fibrosis, suggesting pathologic interactions between gonadal hormones and gut microbiota on lung fibrosis severity. Analysis in female sarcoidosis patients revealed a significant reduction in pSTAT3 and IL-17A levels and a concomitant increase in TGF-{beta}1 levels in CD4+ T cells, compared to male sarcoidosis patients. These studies reveal that estrogen is profibrotic in females and that gut dysbiosis in menstruating females augments lung fibrosis severity, supporting a critical interaction between gonadal hormones and gut flora in lung fibrosis pathogenesis.

immunology↗

bioRxiv2021

The Most Widespread Phage in Animals: Genomics and Taxonomic Classification of Phage WO

Wolbachia are the most common obligate, intracellular bacteria in animals. They exist worldwide in arthropod and nematode hosts in which they commonly act as reproductive parasites or mutualists, respectively. Bacteriophage WO, the largest of Wolbachias mobile elements, includes reproductive parasitism genes, serves as a hotspot for genetic divergence and genomic rearrangement of the bacterial chromosome, and uniquely encodes a Eukaryotic Association Module with eukaryotic-like genes and an ensemble of putative host interaction genes. Despite WOs relevance to genome evolution, selfish genetics, and symbiotic applications, relatively little is known about its origin, host range, diversification, and taxonomic classification. Here we analyze the most comprehensive set of 150 Wolbachia and phage WO assemblies to provide a framework for discretely organizing and naming integrated phage WO genomes. We demonstrate that WO is principally in arthropod Wolbachia with relatives in diverse endosymbionts and metagenomes, organized into four variants related by gene synteny, often oriented opposite the origin of replication in the Wolbachia chromosome, and the large serine recombinase is an ideal typing tool to assign taxonomic classification of the four variants. We identify a novel, putative lytic cassette and WOs association with a conserved eleven gene island, termed Undecim Cluster, that is enriched with virulence-like genes. Finally, we evaluate WO-like Islands in the Wolbachia genome and discuss a new model in which Octomom, a notable WO-like Island, arose from a split with WO. Together, these findings establish the first comprehensive Linnaean taxonomic classification of endosymbiont phages that includes distinguishable genera of phage WO, a family of non-Wolbachia phages from aquatic environments, and an order that captures the collective relatedness of these viruses.

genomics↗