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    The involvement of the low-oxygen-activated locus of Burkholderia cenocepacia in adaptation during cystic fibrosis infection


    Cullen, Louise and O'Connor, Andrew and McCormack, Sarah and Owens, Rebecca A. and Holt, Giles S. and Collins, Cassandra and Callaghan, Maire and Doyle, Sean and Smith, Darren and Schaffer, Kirsten and Fitzpatrick, David A. and McClean, Siobhan (2018) The involvement of the low-oxygen-activated locus of Burkholderia cenocepacia in adaptation during cystic fibrosis infection. Scientific Reports, 8 (1). p. 13386. ISSN 2045-2322

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    Abstract

    Chronic infection with opportunistic pathogens including Burkholderia cepacia complex (Bcc) is a hallmark of cystic fibrosis (CF). We investigated the adaptive mechanisms facilitating chronic lung infection in sequential Bcc isolates from two siblings with CF (P1 and P2), one of whom also experienced intermittent blood-stream infections (P2). We previously showed increased lung cell attachment with colonisation time in both P1 and P2. WGS analysis confirmed that the isolates are closely related. Twelve genes showed three or more mutations, suggesting these were genes under selection. Single nucleotide polymorphisms (SNVs) in 45 regulatory genes were also observed. Proteomic analysis showed that the abundance of 149 proteins increased over 61-months in sputum isolates, and both time- and source-related alterations in protein abundance between the second patient’s isolates. A consistent time-dependent increase in abundance of 19 proteins encoded by a low-oxygen-activated (lxa) locus was observed in both sets of isolates. Attachment was dramatically reduced in a B. cenocepacia K56-2Δlxa-locus deletion mutant, further indicating that it encodes protein(s) involved in host-cell attachment. Time-related changes in virulence in Galleria mellonella or motility were not observed. We conclude that the lxa-locus, associated with anoxic persistence in vitro, plays a role in host-cell attachment and adaptation to chronic colonization in the hypoxic niche of the CF lung.

    Item Type: Article
    Additional Information: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
    Keywords: bacterial evolution; infection; Burkholderia cenocepacia; adaptation; cystic fibrosis;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11055
    Identification Number: https://doi.org/10.1038/s41598-018-31556-6
    Depositing User: David Fitzpatrick
    Date Deposited: 18 Sep 2019 14:04
    Journal or Publication Title: Scientific Reports
    Publisher: Nature Publishing Group
    Refereed: Yes
    URI:

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