Journal article
In Vivo Gene Essentiality and Metabolism in Bordetella pertussis
mSphere, Vol.4(3), p.e00694-18
05/01/2019
DOI: 10.1128/mSphere.00694-18
PMCID: PMC6531889
PMID: 31118307
Abstract
Our study describes the first
in vivo
transposon sequencing (Tn-seq) analysis of
B. pertussis
and identifies genes predicted to be essential for
in vivo
growth in a murine model of intranasal infection, generating key resources for future investigations into
B. pertussis
pathogenesis and vaccine design.
Bordetella pertussis
is the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms of
B. pertussis
growth and pathogenicity. While previous studies have provided insight into
in vitro
gene essentiality of this organism, very little is known about
in vivo
gene essentiality, a critical gap in knowledge, since
B. pertussis
has no previously identified environmental reservoir and is isolated from human respiratory tract samples. We hypothesize that the metabolic capabilities of
B. pertussis
are especially tailored to the respiratory tract and that many of the genes involved in
B. pertussis
metabolism would be required to establish infection
in vivo
. In this study, we generated a diverse library of transposon mutants and then used it to probe gene essentiality
in vivo
in a murine model of infection. Using the CON-ARTIST pipeline, 117 genes were identified as conditionally essential at 1 day postinfection, and 169 genes were identified as conditionally essential at 3 days postinfection. Most of the identified genes were associated with metabolism, and we utilized two existing genome-scale metabolic network reconstructions to probe the effects of individual essential genes on biomass synthesis. This analysis suggested a critical role for glucose metabolism and lipooligosaccharide biosynthesis
in vivo
. This is the first genome-wide evaluation of
in vivo
gene essentiality in
B. pertussis
and provides tools for future exploration.
IMPORTANCE
Our study describes the first
in vivo
transposon sequencing (Tn-seq) analysis of
B. pertussis
and identifies genes predicted to be essential for
in vivo
growth in a murine model of intranasal infection, generating key resources for future investigations into
B. pertussis
pathogenesis and vaccine design.
Details
- Title: Subtitle
- In Vivo Gene Essentiality and Metabolism in Bordetella pertussis
- Creators
- Laura A GonyarPatrick E GelbachDennis G McDuffieAlexander F KoeppelQing ChenGloria LeeLouise M TempleScott StibitzErik L HewlettJason A PapinF. Heath DamronJoshua C Eby
- Resource Type
- Journal article
- Publication Details
- mSphere, Vol.4(3), p.e00694-18
- DOI
- 10.1128/mSphere.00694-18
- PMID
- 31118307
- PMCID
- PMC6531889
- NLM abbreviation
- mSphere
- ISSN
- 2379-5042
- eISSN
- 2379-5042
- Publisher
- American Society for Microbiology
- Grant note
- ; HHSN272201200005C-416476 / ; 5R01AI18000-33 / ;
- Alternative title
- In Vivo Tn-seq in B. pertussis
- Language
- English
- Date published
- 05/01/2019
- Academic Unit
- Iowa Neuroscience Institute; Immunology; Internal Medicine
- Record Identifier
- 9984071993402771
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