Skip to content

Research at St Andrews

Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei

Research output: Contribution to journalArticle

DOI

Author(s)

Narisara Chantratita, Drew A. Rholl, Bernice Sim, Vanaporn Wuthiekanun, Direk Limmathurotsakul, Premjit Amornchai, Aunchalee Thanwisai, Hui Hoon Chua, Wen Fong Ooi, Matthew T. G. Holden, Nicholas P. Day, Patrick Tan, Herbert P. Schweizer, Sharon J. Peacock

School/Research organisations

Abstract

Known mechanisms of resistance to beta-lactam antibiotics include beta-lactamase expression, altered drug target, decreased bacterial permeability, and increased drug efflux. Here, we describe a unique mechanism of beta-lactam resistance in the biothreat organism Burkholderia pseudomallei (the cause of melioidosis), associated with treatment failure during prolonged ceftazidime therapy of natural infection. Detailed comparisons of the initial ceftazidime-susceptible infecting isolate and subsequent ceftazidime-resistant variants from six patients led us to identify a common, large-scale genomic loss involving a minimum of 49 genes in all six resistant strains. Mutational analysis of wild-type B. pseudomallei demonstrated that ceftazidime resistance was due to deletion of a gene encoding a penicillin-binding protein 3 (BPSS1219) present within the region of genomic loss. The clinical ceftazidime-resistant variants failed to grow using commonly used laboratory culture media, including commercial blood cultures, rendering the variants almost undetectable in the diagnostic laboratory. Melioidosis is notoriously difficult to cure and clinical treatment failure is common in patients treated with ceftazidime, the drug of first choice across most of Southeast Asia where the majority of cases are reported. The mechanism described here represents an explanation for ceftazidime treatment failure, and may be a frequent but undetected resistance event.

Close

Details

Original languageEnglish
Pages (from-to)17165-17170
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number41
DOIs
Publication statusPublished - 11 Oct 2011

    Research areas

  • SMALL-COLONY VARIANTS, PSEUDOMONAS-PSEUDOMALLEI, ESCHERICHIA-COLI, BETA-LACTAMASES, MELIOIDOSIS, SUSCEPTIBILITY, DIVISION, BACTERIA, INFECTIONS, AERUGINOSA

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Genomic identification of cryptic susceptibility to penicillins and β-lactamase inhibitors in methicillin-resistant Staphylococcus aureus

    Harrison, E. M., Ba, X., Coll, F., Blane, B., Restif, O., Carvell, H., Köser, C. U., Jamrozy, D., Reuter, S., Lovering, A., Gleadall, N., Bellis, K. L., Uhlemann, A. C., Lowy, F. D., Massey, R. C., Grilo, I. R., Sobral, R., Larsen, J., Rhod Larsen, A., Vingsbo Lundberg, C. & 5 othersParkhill, J., Paterson, G. K., Holden, M. T. G., Peacock, S. J. & Holmes, M. A., 24 Jun 2019, In : Nature Microbiology. 15 p.

    Research output: Contribution to journalArticle

  2. Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics

    Davies, M. R., McIntyre, L., Mutreja, A., Lacey, J. A., Lees, J. A., Towers, R. J., Duchêne, S., Smeesters, P. R., Frost, H. R., Price, D. J., Holden, M. T. G., David, S., Giffard, P. M., Worthing, K. A., Seale, A. C., Berkley, J. A., Harris, S. R., Rivera-Hernandez, T., Berking, O., Cork, A. J. & 18 othersTorres, R. S. L. A., Lithgow, T., Strugnell, R. A., Bergmann, R., Nitsche-Schmitz, P., Chhatwal, G. S., Bentley, S. D., Fraser, J. D., Moreland, N. J., Carapetis, J. R., Steer, A. C., Parkhill, J., Saul, A., Williamson, D. A., Currie, B. J., Tong, S. Y. C., Dougan, G. & Walker, M. J., Jun 2019, In : Nature Genetics. 51, 6, p. 1035-1043

    Research output: Contribution to journalArticle

  3. Antimicrobial resistance in atopic dermatitis: need for an urgent rethink

    Harkins, C. P., Holden, M. T. G. & Irvine, A. D., Mar 2019, In : Annals of Allergy Asthma & Immunology. 122, 3, p. 236-240 5 p.

    Research output: Contribution to journalArticle

  4. Molecular epidemiology and expression of capsular polysaccharides in Staphylococcus aureus clinical isolates in the United States

    Mohamed, N., Timofeyeva, Y., Jamrozy, D., Rojas, E., Hao, L., Silmon de Monerri, N. C., Hawkins, J., Singh, G., Cai, B., Liberator, P., Sebastian, S., Donald, R. G. K., Scully, I. L., Jones, C. H., Creech, C. B., Thomsen, I., Parkhill, J., Peacock, S. J., Jansen, K. U., Holden, M. T. G. & 1 othersAnderson, A. S., 14 Jan 2019, In : PLoS ONE. 14, 1, 33 p., e0208356.

    Research output: Contribution to journalArticle

Related by journal

  1. Proceedings of the National Academy of Sciences of the United States of America (Journal)

    Michael Martin Nevels (Guest editor)
    Jul 2016 → …

    Activity: Publication peer-review and editorial work typesEditor of research journal

  2. Proceedings of the National Academy of Sciences of the United States of America (Journal)

    Oscar Eduardo Gaggiotti (Member of editorial board)
    1 Jan 2013 → …

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

  3. Proceedings of the National Academy of Sciences of the United States of America (Journal)

    Terry K Smith (Member of editorial board)
    2012 → …

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

  4. Proceedings of the National Academy of Sciences of the United States of America (Journal)

    Terry K Smith (Member of editorial board)
    2008 → …

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

  5. Proceedings of the National Academy of Sciences of the United States of America (Journal)

    Gareth Brian Miles (Reviewer)
    2006 → …

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

Related by journal

  1. Acute social isolation alters neurogenomic state in songbird forebrain

    George, J., Bell, Z., Condliffe, D., Doher, K., Abaurrea, T., Spencer, K., Leitao, A., Gahr, M., Hurd, P. & Clayton, D. F., 22 Jul 2019, In : Proceedings of the National Academy of Sciences of the United States of America. Latest Articles

    Research output: Contribution to journalArticle

  2. Asymmetries between achromatic and chromatic extraction of 3D motion signals

    Kaestner, M., Maloney, R., Wailes-Newson, K., Bloj, M., Harris, J., Morland, A. & Wade, A., 17 Jun 2019, In : Proceedings of the National Academy of Sciences of the United States of America. Latest Articles, 10 p.

    Research output: Contribution to journalArticle

  3. Limited oxygen production in the Mesoarchean ocean

    Ossa Ossa, F., Hofmann, A., Spangenberg, J. E., Poulton, S. W., Stüeken, E. E., Schoenberg, R., Eickmann, B., Wille, M., Butler, M. & Bekker, A., 2 Apr 2019, In : Proceedings of the National Academy of Sciences of the United States of America. 116, 14, p. 6647-6652 6 p.

    Research output: Contribution to journalArticle

  4. Scleral pigmentation leads to conspicuous, not cryptic, eye morphology in chimpanzees

    Perea-García, J. O., Kret, M. E., Monteiro, A. & Hobaiter, C., 3 Sep 2019, In : Proceedings of the National Academy of Sciences of the United States of America. Latest Articles, 3 p., 201911410 .

    Research output: Contribution to journalArticle

ID: 74261481