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• W4214679239 abstract "ABSTRACT Neisseria gonorrhoeae (the gonococcus, Gc) is the causative agent of the sexually transmitted infection gonorrhea. Gc is a prominent threat to human health by causing severe and lifelong clinical sequelae, including infertility and chronic pelvic pain, which is amplified by the emergence of “superbug” strains that are resistant to all current antibiotics. Gc is highly adapted to colonize human mucosal surfaces, where it survives despite initiating a robust inflammatory response and influx of polymorphonuclear leukocytes (PMNs or neutrophils) that typically clear bacteria. Here, dual-species RNA-sequencing (RNA-seq) was used to define Gc and PMN transcriptional profiles alone and after infection. Three strains of Gc and three human donors’ transcriptional responses were assessed to characterize core host and bacterial responses. Comparative analysis of Gc transcripts revealed major overlap between the Gc response to PMNs, iron, and hydrogen peroxide; specifically, the TonB system and TonB dependent transporters (TDT) were upregulated in response to PMNs. We experimentally confirmed that induction of the iron-dependent TDT TbpB is responsive to the presence of PMNs and that tonB is required for Gc survival from PMNs. Pathway analysis of PMN transcripts induced by Gc infection revealed differential expression of genes driving pathways involved in cell adhesion and migration, inflammatory responses, and inflammation resolution. Production of pro-inflammatory cytokines, including IL1B and IL8, the adhesion factor ICAM1, and the anti-inflammatory prostaglandin PGE2 was confirmed to be induced in PMNs in response to Gc. Together, this study represents a comprehensive and experimentally validated dual-species transcriptomic analysis of three isolates of Gc and primary human PMNs that gives insight into how this bacterium survives innate immune onslaught to cause disease in humans." @default.
• W4214679239 created "2022-03-02" @default.
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• W4214679239 date "2022-02-28" @default.
• W4214679239 modified "2023-10-16" @default.
• W4214679239 title "Dual species transcriptomics reveals core metabolic and immunologic processes in the interaction between primary human neutrophils and<i>Neisseria gonorrhoeae</i>strains" @default.
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• W4214679239 doi "https://doi.org/10.1101/2022.02.28.482360" @default.
• W4214679239 hasPublicationYear "2022" @default.
• W4214679239 type Work @default.

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