Virulence mechanisms of Streptococcus pneumoniae during co-infection

Streptococcus pneumoniae (pneumococcus) represents a key clinical challenge, being a major global cause of morbidity and mortality. Typically existing as a nasopharyngeal commensal, pneumococcus undergoes significant metabolic changes during its switch to a virulent pathogen, when it can cause severe pneumoniae, bacteriemia and meningitis. This switch is poorly understood but is thought to be influenced by environmental signals arising from co-infections between pneumococcus and other bacteria as well as viruses in the nasopharynx. This review provides a comprehensive overview of the multi-stage progression of pneumococcal invasive disease, from initial colonisation to host barrier migration. We examine environmental triggers that drive the lifestyle switch from commensal to virulent, highlighting the role of other organisms in this stimulation. In particular, we focus on influenza A and respiratory syncytial virus, as well as other bacteria including Staphylococcus aureus, Moraxella catarrhalis and Haemophilus influenzae. Overall, we bring the current understanding of the field into the context of the growing antimicrobial resistance global threat, demonstrating that understanding these complex cross-species interactions is vital for developing clinical interventions against secondary pneumococcal infections.