Genome sequencing of disease and carriage isolates of nontypeable Haemophilus influenzae identifies discrete population structure.
One of the main hurdles for the development of an effective and broadly protective vaccine against nonencapsulated isolates of Haemophilus influenzae (NTHi) lies in the genetic diversity of the species, which renders extremely difficult the identification of cross-protective candidate antigens. To assess whether a population structure of NTHi could be defined, we performed genome sequencing of a collection of diverse clinical isolates representative of both carriage and disease and of the diversity of the natural population. Analysis of the distribution of polymorphic sites in the core genome and of the composition of the accessory genome defined distinct evolutionary clades and supported a predominantly clonal evolution of NTHi, with the majority of genetic information transmitted vertically within lineages. A correlation between the population structure and the presence of selected surface-associated proteins and lipooligosaccharide structure, known to contribute to virulence, was found. This high-resolution, genome-based population structure of NTHi provides the foundation to obtain a better understanding, of NTHi adaptation to the host as well as its commensal and virulence behavior, that could facilitate intervention strategies against disease caused by this important human pathogen.
Novartis Vaccines, 53100 Siena, Italy.
Matteo
M
De Chiara
Derek
D
Hood
Alessandro
A
Muzzi
Derek J
DJ
Pickard
Tim
T
Perkins
Mariagrazia
M
Pizza
Gordon
G
Dougan
Rino
R
Rappuoli
E Richard
ER
Moxon
Marco
M
Soriani
Claudio
C
Donati
D002353:Carrier State; D016680:Genome, Bacterial; D006193:Haemophilus influenzae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D010802:Phylogeny
NTHi; genomics; population genetics