Characterization of nontypable haemophilus influenzae isolates recovered from adult patients with underlying chronic lung disease reveals genotypic and phenotypic traits associated with persistent infection

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dc.contributor.authorGarmendia García, Juncal
dc.contributor.authorViadas Martínez, Cristina
dc.contributor.authorCalatayud, Laura
dc.contributor.authorMell, Joshua Chang
dc.contributor.authorMartí Lliteras, Pau
dc.contributor.authorEuba, Begoña
dc.contributor.authorLlobet, Enrique
dc.contributor.authorGil Puig, Carmen
dc.contributor.authorBengoechea Alonso, José Antonio
dc.contributor.authorRedfield, Rosemary J.
dc.contributor.authorLiñares, Josefina
dc.contributor.departmentIdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutuaes_ES
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernua, 359/2012es
dc.date.accessioned2018-09-06T12:20:23Z
dc.date.available2018-09-06T12:20:23Z
dc.date.issued2014
dc.description.abstractNontypable 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.en
dc.description.sponsorshipJCM 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.en
dc.format.mimetypeapplication/pdfen
dc.format.mimetypeapplication/zipen
dc.identifier.doi10.1371/journal.pone.0097020
dc.identifier.issn1932-6203
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/30556
dc.language.isoengen
dc.publisherPublic Library of Scienceen
dc.relation.ispartofPlos One, 9(5): e97020en
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO//SAF2012-31166/ES/
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0097020
dc.rights© 2014 Garmendia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectNontypable Haemophilus influenzae (NTHi)en
dc.subjectPersistent infectionsen
dc.titleCharacterization of nontypable haemophilus influenzae isolates recovered from adult patients with underlying chronic lung disease reveals genotypic and phenotypic traits associated with persistent infectionen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication6018a4d2-1ded-494f-92de-2ca4cebbe693
relation.isAuthorOfPublication7fcbe5e9-956a-431c-95c6-1c988099207c
relation.isAuthorOfPublication.latestForDiscovery6018a4d2-1ded-494f-92de-2ca4cebbe693

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