Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts.
Animals
Disease Models, Animal
Ferrets
Genetic Testing
High-Throughput Screening Assays
Infectious Disease Transmission, Vertical
/ prevention & control
Mice
Mutagenesis, Insertional
Pneumococcal Infections
/ microbiology
Pneumococcal Vaccines
/ administration & dosage
Sequence Analysis, DNA
Streptococcus pneumoniae
/ genetics
Vaccines, Synthetic
/ administration & dosage
Virulence Factors
/ genetics
Streptococcus pneumoniae
ferret
influenza
transmission
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
12 06 2019
12 06 2019
Historique:
received:
08
08
2018
revised:
18
02
2019
accepted:
02
04
2019
pubmed:
28
5
2019
medline:
24
12
2019
entrez:
26
5
2019
Statut:
ppublish
Résumé
The capacity of Streptococcus pneumoniae to successfully transmit and colonize new human hosts is a critical aspect of pneumococcal population biology and a prerequisite for invasive disease. However, the bacterial mechanisms underlying this process remain largely unknown. To identify bacterial factors required for transmission, we conducted a high-throughput genetic screen with a transposon sequencing (Tn-seq) library of a pneumococcal strain in a ferret transmission model. Key players in both metabolism and transcriptional regulation were identified as required for efficient bacterial transmission. Targeted deletion of the putative C3-degrading protease CppA, iron transporter PiaA, or competence regulatory histidine kinase ComD significantly decreased transmissibility in a mouse model, further validating the screen. Maternal vaccination with recombinant surface-exposed PiaA and CppA alone or in combination blocked transmission in offspring and were more effective than capsule-based vaccines. These data underscore the possibility of targeting pneumococcal transmission as a means of eliminating invasive disease in the population.
Identifiants
pubmed: 31126758
pii: S1931-3128(19)30215-X
doi: 10.1016/j.chom.2019.04.012
pmc: PMC6598203
mid: NIHMS1528020
pii:
doi:
Substances chimiques
Pneumococcal Vaccines
0
Vaccines, Synthetic
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
884-891.e6Subventions
Organisme : NIAID NIH HHS
ID : R01 AI110618
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI117247
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI124302
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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