Journal Article

Multispecies transcriptomics reveals influenza A virus modulation of Streptococcus pneumoniae EF3030 infection in human lung epithelium and murine lung

Earnhardt, Erin Y., Im, Hansol, Martínez, Eriel, Lane, Jessica R., Roussey, Holly N., Tipper, Jennifer L., D'Mello, Adonis, Prokopczuk, Federico I., Tettelin, Hervé, Harrod, Kevin S., Orihuela, Carlos J.

2026

Overview

Transition from pneumococcal colonization to invasive disease is not well understood. Studies have shown that such a transition can occur as a result of influenza A virus (IAV) coinfection. We investigated the pneumococcal (serotype 19F, strain EF3030, and isogenic mutants) and airway epithelial transcriptomes with and without IAV (A/California/07 2009 pH1N1) infection. Pneumococcus and influenza coinfection leads to enhanced bacterial transcriptional programs related to growth, nutrient availability, and energy biosynthesis, suggesting conversion to an invasive phenotype. Influenza-induced secondary EF3030 infection influences human bronchial epithelial cell (HBEC) microtubules and extracellular matrix. Notably, sialic acid (NanR) utilization is a central regulon in EF3030 mono/coinfection with pH1N1 on HBEC. Downregulation of sialic acid utilization during influenza coinfection improved Spn pathogenicity ex vivo but did not alter disease in vivo, suggesting other metabolic cues are also important. This study uncovers critical metabolic features of the EF3030-pH1N1 interface to inform how Spn proliferates during IAV coinfection.

• Publisher: American Society for Microbiology,American Society for Microbiology (ASM)
• Subject: Animals / Bacterial infections / Bacterial Pathogenesis / Bronchopulmonary infection / Cell differentiation / Cilia / Clinical Microbiology and Infectious Diseases / co-infection / Coinfection - microbiology / Coinfection - virology / Colonization / Disease Models, Animal / Down-regulation / Epithelial cells / Epithelial Cells - microbiology / Epithelial Cells - virology / Epithelium / Extracellular matrix / Female / Gene expression / Gene Expression Profiling / Genomes / Host-Microbial Interactions / Host-Pathogen Interactions / Humans / Influenza / Influenza A / Influenza A virus - physiology / Influenza A Virus, H1N1 Subtype / Influenza Viruses / Influenza, Human / Invasiveness / Lung - microbiology / Lung - virology / Lungs / Metabolic pathways / Mice / Microbial Pathogenesis and Immunology / Microtubules / Nasopharynx / Nutrient availability / Pathogenesis of Influenza / Pathogenicity / Phenotypes / Pneumococcal Infections - microbiology / Pneumococcal Infections - virology / Pneumococcal Pathogenesis / Pneumonia / primary human lung cells / Protein families / Research Article / Respiratory Infections / Streptococcus infections / Streptococcus pneumoniae / Streptococcus pneumoniae - genetics / Streptococcus pneumoniae - pathogenicity / Transcriptome / Transcriptomes / Transcriptomics / Virology / Virulence