Capillary leakage provides nutrients and antioxidants for rapid pneumococcal proliferation in influenza-infected lower airways.

Sender V, Hentrich K, Pathak A, Tan Qian Ler A, Embaie BT, Lundström SL, Gaetani M, Bergstrand J, Nakamoto R, Sham L, Widengren J, Normark S, Henriques-Normark B

Proc. Natl. Acad. Sci. U.S.A. 117 (49) 31386-31397 [2020-12-08; online 2020-11-23]

Influenza A virus (IAV)-related mortality is often due to secondary bacterial infections, primarily by pneumococci. Here, we study how IAV-modulated changes in the lungs affect bacterial replication in the lower respiratory tract (LRT). Bronchoalveolar lavages (BALs) from coinfected mice showed rapid bacterial proliferation 4 to 6 h after pneumococcal challenge. Metabolomic and quantitative proteomic analyses demonstrated capillary leakage with efflux of nutrients and antioxidants into the alveolar space. Pneumococcal adaptation to IAV-induced inflammation and redox imbalance increased the expression of the pneumococcal chaperone/protease HtrA. Presence of HtrA resulted in bacterial growth advantage in the IAV-infected LRT and protection from complement-mediated opsonophagocytosis due to capsular production. Absence of HtrA led to growth arrest in vitro that was partially restored by antioxidants. Pneumococcal ability to grow in the IAV-infected LRT depends on the nutrient-rich milieu with increased levels of antioxidants such as ascorbic acid and its ability to adapt to and cope with oxidative damage and immune clearance.

Bioinformatics Support for Computational Resources [Service]

Chemical Proteomics [Collaborative]

PubMed 33229573

DOI 10.1073/pnas.2012265117

Crossref 10.1073/pnas.2012265117

pii: 2012265117
pmc: PMC7733805