Characterization of nontypable haemophilus influenzae isolates recovered from adult patients with underlying chronic lung disease reveals genotypic and phenotypic traits associated with persistent infection
Fecha
2014Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Impacto
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10.1371/journal.pone.0097020
Resumen
Nontypable Haemophilus influenzae (NTHi) has emerged as an important opportunistic pathogen causing infection in adults
suffering obstructive lung diseases. Existing evidence associates chronic infection by NTHi to the progression of the chronic
respiratory disease, but specific features of NTHi associated with persistence have not been comprehensively addressed. To
provide clues about adaptiv ...
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Nontypable Haemophilus influenzae (NTHi) has emerged as an important opportunistic pathogen causing infection in adults
suffering obstructive lung diseases. Existing evidence associates chronic infection by NTHi to the progression of the chronic
respiratory disease, but specific features of NTHi associated with persistence have not been comprehensively addressed. To
provide clues about adaptive strategies adopted by NTHi during persistent infection, we compared sequential persistent
isolates with newly acquired isolates in sputa from six patients with chronic obstructive lung disease. Pulse field gel
electrophoresis (PFGE) identified three patients with consecutive persistent strains and three with new strains. Phenotypic
characterisation included infection of respiratory epithelial cells, bacterial self-aggregation, biofilm formation and resistance
to antimicrobial peptides (AMP). Persistent isolates differed from new strains in showing low epithelial adhesion and
inability to form biofilms when grown under continuous-flow culture conditions in microfermenters. Self-aggregation
clustered the strains by patient, not by persistence. Increasing resistance to AMPs was observed for each series of persistent
isolates; this was not associated with lipooligosaccharide decoration with phosphorylcholine or with lipid A acylation.
Variation was further analyzed for the series of three persistent isolates recovered from patient 1. These isolates displayed
comparable growth rate, natural transformation frequency and murine pulmonary infection. Genome sequencing of these
three isolates revealed sequential acquisition of single-nucleotide variants in the AMP permease sapC, the heme acquisition
systems hgpB, hgpC, hup and hxuC, the 3-deoxy-D-manno-octulosonic acid kinase kdkA, the long-chain fatty acid transporter
ompP1, and the phosphoribosylamine glycine ligase purD. Collectively, we frame a range of pathogenic traits and a
repertoire of genetic variants in the context of persistent infection by NTHi. [--]
Materias
Nontypable Haemophilus influenzae (NTHi),
Persistent infections
Editor
Public Library of Science
Publicado en
Plos One, 9(5): e97020
Departamento
Universidad Pública de Navarra/Nafarroako Unibertsitate Publikoa. IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
Versión del editor
Entidades Financiadoras
JCM was supported by a postdoctoral fellowship from the U.S. National Institutes of Health (5F32AI084427). This work has been funded by grants from ISCIII PS09/00130, Ministerio Economía y Competitividad (MINECO) SAF2012-31166, Dpto. Salud Gobierno Navarra 359/2012, and Ministerio Educación PRX 12/00191 to JG, PS09/01904 to JL, and Canadian Institutes of Health Research grant to RJR. CIBERES is an initiative from ISCIII, Spain.