title: Single Cell Bottlenecks in the Pathogenesis of Streptococcus pneumoniae.
abstract: 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.
authors.affiliation: Department of Microbiology, New York University, New York, New York, United States of America.|Department of Otolaryngology-Head and Neck Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Masamitsu
authors.identifier: http://orcid.org/0000-0002-7896-4892
authors.initials: M
authors.lastname: Kono
authors.affiliation: Department of Microbiology, New York University, New York, New York, United States of America.
authors.forename: M Ammar
authors.initials: MA
authors.lastname: Zafar
authors.affiliation: Department of Microbiology, New York University, New York, New York, United States of America.
authors.forename: Marisol
authors.initials: M
authors.lastname: Zuniga
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Roche
authors.affiliation: Department of Microbiology, New York University, New York, New York, United States of America.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hamaguchi
authors.affiliation: Department of Microbiology, New York University, New York, New York, United States of America.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
mesh_terms: D000818:Animals; D060085:Coinfection / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D009980:Influenza A virus; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000635:transmission*; D013296:Streptococcus pneumoniae