Journal article
Dual species transcriptomics reveals conserved metabolic and immunologic processes in interactions between human neutrophils and Neisseria gonorrhoeae
PLoS pathogens, Vol.20(7), p.e1012369
07/08/2024
DOI: 10.1371/journal.ppat.1012369
PMCID: PMC11257400
PMID: 38976720
Abstract
Neisseria gonorrhoeae (the gonococcus, Gc) causes the sexually transmitted infection gonorrhea. Gc is a prominent threat to human health by causing severe lifelong sequelae, including infertility and chronic pelvic pain, which is amplified by the emergence of "superbug" strains 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, neutrophils) that typically clear bacteria. Here, dual-species RNA-sequencing was used to define Gc and PMN transcriptional profiles alone and after infection. Core host and bacterial responses were assessed for two strains of Gc and three human donors' PMNs. Comparative analysis of Gc transcripts revealed overlap between Gc responses to PMNs, iron, and hydrogen peroxide; 98 transcripts were differentially expressed across both Gc strains in response to PMN co-culture, including iron-responsive and oxidative stress response genes. We experimentally determined that the iron-dependent TbpB is suppressed by PMN co-culture, and iron-limited Gc have a survival advantage when cultured with PMNs. Analysis of PMN transcripts modulated by Gc infection revealed differential expression of genes driving cell adhesion, migration, inflammatory responses, and inflammation resolution pathways. Production of pro-inflammatory cytokines, including IL1B and IL8, the adhesion factor ICAM1, and prostaglandin PGE2 were induced in PMNs in response to Gc. Together, this study represents a comprehensive and experimentally validated dual-species transcriptomic analysis of two isolates of Gc and primary human PMNs that gives insight into how this bacterium survives innate immune onslaught to cause disease.
Details
- Title: Subtitle
- Dual species transcriptomics reveals conserved metabolic and immunologic processes in interactions between human neutrophils and Neisseria gonorrhoeae
- Creators
- Aimee D. Potter - University of VirginiaVonetta L. Edwards - University of Maryland, BaltimoreAdonis D'Mello - University of Maryland, BaltimoreMary C. Gray - University of VirginiaAmol C. Shetty - University of Maryland, BaltimoreAmy L. Forehand - University of VirginiaCamille S. Westlake - University of VirginiaEvan R. Lamb - University of VirginiaXuechu Zhao - University of Maryland, BaltimoreStephanie A. Ragland - University of VirginiaAlison K. Criss - University of VirginiaHerve Tettelin - University of Maryland, Baltimore
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.20(7), p.e1012369
- Publisher
- Public Library Science
- DOI
- 10.1371/journal.ppat.1012369
- PMID
- 38976720
- PMCID
- PMC11257400
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Number of pages
- 25
- Grant note
- University of Virginia Robert R. Wagner Fellowship National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) U19AI110820 / Department of Health and Human Services R21AI130646; T32AI007496; R01AI097312; R01AI127793; R21AI161302; U19AI094044; T32AI007046; T32 GM007267; F30 AI179038 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 07/08/2024
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984701825502771
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