Single Cell Bottlenecks in the Pathogenesis of Streptococcus pneumoniae

PLoS Pathogens

Masamitsu Kono¹  Jeffrey N. Weiser¹  Aoife M. Roche¹  Marisol Zuniga¹  Shigeto Hamaguchi²  M. Ammar Zafar³ 

[1] Department of Microbiology, New York University, New York, New York, United States of America;Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;Department of Otolaryngology-Head and Neck Surgery, Wakayama Medical University, Wakayama, Japan

关键词: Influenza A virus;    Bacteremia;    Co-infections;    Blood;    Mouse models;    Pneumococcus;    Sepsis;    Middle ear;   

DOI  :  10.1371/journal.ppat.1005887

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Herein, we studied a virulent isolate of the leading bacterial pathogen Streptococcus pneumoniae in an infant mouse model of colonization, disease and transmission, both with and without influenza A (IAV) co-infection. To identify vulnerable points in the multiple steps involved in pneumococcal pathogenesis, this model was utilized for a comprehensive analysis of population bottlenecks. Our findings reveal that in the setting of IAV co-infection the organism must pass through single cell bottlenecks during bloodstream invasion from the nasopharynx within the host and in transmission between hosts. Passage through these bottlenecks was not associated with genetic adaptation by the pathogen. The bottleneck in transmission occurred between bacterial exit from one host and establishment in another explaining why the number of shed organisms in secretions is critical to overcoming it. These observations demonstrate how viral infection, and TLR-dependent innate immune responses it stimulates and that are required to control it, drive bacterial contagion.

【 授权许可】

CC BY