Academic Journal
Influenza A virus co-infection alters Streptococcus pneumoniae gene expression during upper respiratory tract colonization.
| Title: | Influenza A virus co-infection alters Streptococcus pneumoniae gene expression during upper respiratory tract colonization. |
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| Authors: | Nutter NA; Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Costa-Terryll A; Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Miller LM; Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Leung M; Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina, USA., Zhang P; Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina, USA., Islam MM; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA., Fecko D; Department of Microbiology, New York University School of Medicine, New York, New York, USA., Zafar MA; Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA. |
| Source: | Infection and immunity [Infect Immun] 2026 Oct 13; Vol. 94 (10), pp. e0032326. Date of Electronic Publication: 2026 Sep 01. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0246127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5522 (Electronic) Linking ISSN: 00199567 NLM ISO Abbreviation: Infect Immun Subsets: MEDLINE |
| Imprint Name(s): | Publication: Washington, DC : American Society For Microbiology Original Publication: [Bethesda, Md.] American Society for Microbiology. |
| MeSH Terms: | Streptococcus pneumoniae*/genetics , Coinfection*/microbiology , Coinfection*/virology , Influenza A virus*/physiology , Pneumococcal Infections*/microbiology , Orthomyxoviridae Infections*/virology , Orthomyxoviridae Infections*/complications , Orthomyxoviridae Infections*/microbiology , Respiratory Tract Infections*/microbiology , Gene Expression Regulation, Bacterial*, Nasopharynx/microbiology ; Animals ; Mice ; Gene Expression Profiling ; Disease Models, Animal ; Humans ; Female |
| Abstract: | Streptococcus pneumoniae (Spn) asymptomatically colonizes the upper respiratory tract (URT), a niche from which it can transmit to another host or cause invasive disease in the same host. The in vivo transcriptional adaptations that Spn undergoes during nasopharyngeal colonization, particularly during influenza A virus (IAV) co-infection, are poorly understood. Here, we leveraged an established infant mouse model of colonization, shedding, and transmission to perform genome-wide transcriptomic profiling of Spn during mono- and during IAV co-infection. Compared with broth-grown controls, pneumococci isolated from the URT exhibited distinct transcriptional programs, with over 200 genes differentially expressed across time points. Genes involved in carbohydrate uptake and metabolism, glycan degradation, amino sugar and nucleotide sugar metabolism, and amino acid biosynthesis were consistently enriched during colonization, highlighting metabolic adaptation to the nasopharyngeal niche. In contrast, IAV co-infection induced a markedly distinct transcriptional signature, including upregulation of branched-chain amino acid biosynthesis, bacteriocin production, and phosphate acquisition systems. Notably, the pilus islet-1 locus was upregulated during Spn-IAV co-infection. Functional studies demonstrated that while the pilus was dispensable for colonization under mono- and co-infection conditions, it promoted high-shedding events and enhanced inflammatory responses during IAV co-infection. However, reduced inflammation and reduced high-shedding events from pups inoculated with a pilus-deficient mutant did not alter transmission frequency in the infant mouse model. Collectively, our findings define the in vivo transcriptional landscape of Spn during URT colonization and reveal distinct bacterial adaptations during viral co-infection, providing insight into mechanisms that influence pneumococcal persistence, inflammation, and transmission. |
| Competing Interests: | The authors declare no conflict of interest. |
| Comments: | Update of: bioRxiv. 2026 May 19:2026.05.19.726214. doi: 10.64898/2026.05.19.726214.. (PMID: 42239407) |
| Grant Information: | R21 AI154047 United States AI NIAID NIH HHS; AI154047 National Institute of Allergy and Infectious Diseases; P30CA012197 United States CA NCI NIH HHS |
| Contributed Indexing: | Keywords: RNA-seq; Streptococcus pneumoniae; transmission |
| Entry Date(s): | Date Created: 20260902 Date Completed: 20261013 Latest Revision: 20261013 |
| Update Code: | 20261014 |
| DOI: | 10.1128/iai.00323-26 |
| PMID: | 42684855 |
| Database: | MEDLINE |
| ISSN: | 1098-5522 |
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| DOI: | 10.1128/iai.00323-26 |