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bioRxiv · 10.1101/2025.06.05.658111

Wolbachia induces host cell identity changes and determines symbiotic fate in Drosophila

Jacobs, J.·Mirchandani, C. D.·Seligmann, W. E.·Sacco, S.·Escalona, M.·Green, R. E.·Russell, S.
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Abstract

Host-associated bacteria influence eukaryotic cellular differentiation, but the underlying mechanisms are difficult to disentangle because of cell-type-specific tropisms and phenotypes. The association between Wolbachia pipientis and Drosophila melanogaster offers a tractable system for gaining high-resolution insight into how host and microbe gene expression interact. Using Wolbachia-infected D. melanogaster cell lines, we show that the native wMel strain alters host phenotypic, transcriptomic, and chromatin conformation states. High-throughput imaging reveals that wMel infection differentially alters host cellular phenotypes in a titer-independent manner in some cell lines. These phenotypically altered host cells exhibit differential gene expression complementary to the expression patterns observed in their wMel symbionts. Infection was also negatively associated with chromatin organization and histone modification pathways, prompting us to investigate differences in chromatin conformation between infection states. Micro-C chromatin contact data reveal that wMel infection conferred increased D. melanogaster chromatin contacts coinciding with both increased compartmentalization and derepression. The X chromosome exhibited evidence consistent with altered dosage compensation, with no downstream alteration of the X:autosome transcript ratio or X-linked histone acetylation, consistent with a dosage compensation-mediated male-killing mechanism encoded by wMel that has been suppressed in D. melanogaster. Overall, these findings suggest that the character of Wolbachia symbiosis, cooperative or antagonistic, emerges in response to the host cellular environment. Furthermore, these results demonstrate that in vitro cell lines offer promising avenues for uncovering the functional genetic basis of microbe-induced host phenotypes.

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Jacobs, J., Mirchandani, C. D., Seligmann, W. E., Sacco, S., Escalona, M., Green, R. E., Russell, S.. 2025-06-06. Wolbachia induces host cell identity changes and determines symbiotic fate in Drosophila. https://doi.org/10.1101/2025.06.05.658111

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