Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection
Mirelys Hernandez-Morfa1,2, Nicolas M Reinoso-Vizcaino1,2, Victoria E Zappia1,2
1Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.
Abstract:
Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection.
Insights
Influenza A virus infection enhances the survival of Streptococcus pneumoniae by promoting fluoroquinolone persistence within host cells. This occurs due to increased oxidative stress and impaired autophagy, highlighting challenges in treating coinfections.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- * *Streptococcus pneumoniae* causes severe complications, especially after influenza A virus (IAV) infection.
- * IAV infection increases intracellular survival of *S. pneumoniae* and promotes fluoroquinolone (FQ) persistence.
- * Intracellular FQ persistence is triggered by host cell oxidative stress, allowing bacteria to survive high drug concentrations.
Purpose of the Study:
- * To investigate how IAV infection influences pneumococcal intracellular FQ persistence.
- * To identify host and bacterial factors contributing to this enhanced persistence.
Main Methods:
- * Investigated *S. pneumoniae* survival and FQ persistence in IAV-infected human cells (pneumocytes, macrophages, neutrophils).
- * Assessed oxidative stress levels and autophagy function (autophagosome-lysosome fusion) in infected cells.
- * Identified *S. pneumoniae* genes involved in oxidative stress response using genetic screens.
Main Results:
- * IAV infection significantly enhanced pneumococcal FQ persistence in infected pneumocytes, macrophages, and neutrophils.
- * Increased oxidative stress in IAV-infected cells contributed to enhanced FQ persistence.
- * The phenotype was more pronounced in autophagy-proficient cells, suggesting IAV-induced autophagy blockage plays a role.
- * Several *S. pneumoniae* oxidative stress response genes (*sodA*, *clpL*, *nrdH*, *psaB*) were found to be critical for FQ persistence.
Conclusions:
- * IAV infection creates a cellular environment that promotes *S. pneumoniae* fluoroquinolone persistence.
- * This mechanism involves increased oxidative stress and potentially impaired autophagy.
- * Specific bacterial genes mediating oxidative stress response are crucial for this antibiotic persistence.
- * Findings highlight the need to consider viral-host interactions when treating pneumococcal infections in influenza patients.
More Related Videos
10:47Using Bioluminescent Imaging to Investigate Synergism Between Streptococcus pneumoniae and Influenza A Virus in Infant Mice
Published on: April 14, 2011
07:44Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes
Published on: February 14, 2025
Related Concept Videos
01:28Pneumonia IV: Management
Bacterial Pneumonia Treatment
For bacterial pneumonia, antibiotics serve as the cornerstone of therapy. Initial treatment often begins with empirical antibiotics, tailored to the anticipated causative organism and adjusted based on culture results. Key antibiotic choices include:
01:30Pneumonia I: Introduction
Risk Factors
Various factors influence the likelihood of developing pneumonia. Age plays a crucial role, with infants, children under two, and individuals over 65 at increased risk due to their...
01:30Pneumonia III: Complications and Assessment
01:29Pneumonia II: Pathophysiology