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      Reclassification of the Specialized Metabolite Producer Pseudomonas mesoacidophila ATCC 31433 as a Member of the Burkholderia cepacia Complex

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          ABSTRACT

          Pseudomonas mesoacidophila ATCC 31433 is a Gram-negative bacterium, first isolated from Japanese soil samples, that produces the monobactam isosulfazecin and the β-lactam-potentiating bulgecins. To characterize the biosynthetic potential of P. mesoacidophila ATCC 31433, its complete genome was determined using single-molecule real-time DNA sequence analysis. The 7.8-Mb genome comprised four replicons, three chromosomal (each encoding rRNA) and one plasmid. Phylogenetic analysis demonstrated that P. mesoacidophila ATCC 31433 was misclassified at the time of its deposition and is a member of the Burkholderia cepacia complex, most closely related to Burkholderia ubonensis. The sequenced genome shows considerable additional biosynthetic potential; known gene clusters for malleilactone, ornibactin, isosulfazecin, alkylhydroxyquinoline, and pyrrolnitrin biosynthesis and several uncharacterized biosynthetic gene clusters for polyketides, nonribosomal peptides, and other metabolites were identified. Furthermore, P. mesoacidophila ATCC 31433 harbors many genes associated with environmental resilience and antibiotic resistance and was resistant to a range of antibiotics and metal ions. In summary, this bioactive strain should be designated B. cepacia complex strain ATCC 31433, pending further detailed taxonomic characterization.

          IMPORTANCE This work reports the complete genome sequence of Pseudomonas mesoacidophila ATCC 31433, a known producer of bioactive compounds. Large numbers of both known and novel biosynthetic gene clusters were identified, indicating that P. mesoacidophila ATCC 31433 is an untapped resource for discovery of novel bioactive compounds. Phylogenetic analysis demonstrated that P. mesoacidophila ATCC 31433 is in fact a member of the Burkholderia cepacia complex, most closely related to the species Burkholderia ubonensis. Further investigation of the classification and biosynthetic potential of P. mesoacidophila ATCC 31433 is warranted.

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          Most cited references38

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          The genome of Burkholderia cenocepacia J2315, an epidemic pathogen of cystic fibrosis patients.

          Bacterial infections of the lungs of cystic fibrosis (CF) patients cause major complications in the treatment of this common genetic disease. Burkholderia cenocepacia infection is particularly problematic since this organism has high levels of antibiotic resistance, making it difficult to eradicate; the resulting chronic infections are associated with severe declines in lung function and increased mortality rates. B. cenocepacia strain J2315 was isolated from a CF patient and is a member of the epidemic ET12 lineage that originated in Canada or the United Kingdom and spread to Europe. The 8.06-Mb genome of this highly transmissible pathogen comprises three circular chromosomes and a plasmid and encodes a broad array of functions typical of this metabolically versatile genus, as well as numerous virulence and drug resistance functions. Although B. cenocepacia strains can be isolated from soil and can be pathogenic to both plants and man, J2315 is representative of a lineage of B. cenocepacia rarely isolated from the environment and which spreads between CF patients. Comparative analysis revealed that ca. 21% of the genome is unique in comparison to other strains of B. cenocepacia, highlighting the genomic plasticity of this species. Pseudogenes in virulence determinants suggest that the pathogenic response of J2315 may have been recently selected to promote persistence in the CF lung. The J2315 genome contains evidence that its unique and highly adapted genetic content has played a significant role in its success as an epidemic CF pathogen.
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            Versatility of aminoglycosides and prospects for their future.

            Aminoglycoside antibiotics have had a major impact on our ability to treat bacterial infections for the past half century. Whereas the interest in these versatile antibiotics continues to be high, their clinical utility has been compromised by widespread instances of resistance. The multitude of mechanisms of resistance is disconcerting but also illuminates how nature can manifest resistance when bacteria are confronted by antibiotics. This article reviews the most recent knowledge about the mechanisms of aminoglycoside action and the mechanisms of resistance to these antibiotics.
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              PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance.

              Antimicrobial peptides are distributed throughout the animal kingdom and are a key component of innate immunity. Salmonella typhimurium regulates mechanisms of resistance to cationic antimicrobial peptides through the two-component systems PhoP-PhoQ and PmrA-PmrB. Polymyxin resistance is encoded by the PmrA-PmrB regulon, whose products modify the lipopolysaccharide (LPS) core and lipid A regions with ethanolamine and add aminoarabinose to the 4' phosphate of lipid A. Two PmrA-PmrB-regulated S. typhimurium loci (pmrE and pmrF) have been identified that are necessary for resistance to polymyxin and for the addition of aminoarabinose to lipid A. One locus, pmrE, contains a single gene previously identified as pagA (or ugd) that is predicted to encode a UDP-glucose dehydrogenase. The second locus, pmrF, is the second gene of a putative operon predicted to encode seven proteins, some with similarity to glycosyltransferases and other complex carbohydrate biosynthetic enzymes. Genes immediately flanking this putative operon are also regulated by PmrA-PmrB and/or have been associated with S. typhimurium polymyxin resistance. This work represents the first identification of non-regulatory genes necessary for modification of lipid A and subsequent antimicrobial peptide resistance, and provides support for the hypothesis that lipid A aminoarabinose modification promotes resistance to cationic antimicrobial peptides.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                J Bacteriol
                J. Bacteriol
                jb
                jb
                JB
                Journal of Bacteriology
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                0021-9193
                1098-5530
                24 April 2017
                13 June 2017
                1 July 2017
                13 June 2017
                : 199
                : 13
                : e00125-17
                Affiliations
                [a ]Department of Chemistry, Swansea University, Swansea, United Kingdom
                [b ]School of Chemistry, Cardiff University, Cardiff, United Kingdom
                [c ]School of Biosciences, Cardiff University, Cardiff, United Kingdom
                [d ]Department of Biosciences, Swansea University, Swansea, United Kingdom
                [e ]School of Medicine, Swansea University, Swansea, United Kingdom
                [f ]Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
                [g ]School of Chemistry, University of Bristol, Bristol, United Kingdom
                University of Tennessee at Knoxville
                Author notes
                Address correspondence to E. Joel Loveridge, e.j.loveridge@ 123456swansea.ac.uk , or John Crosby, john.crosby@ 123456bristol.ac.uk .
                [*]

                Present address: Sarah E. Adams, The Francis Crick Institute, London, United Kingdom; Daniel Rodriguez-Martin, Centro de Investigación en Sanidad Animal, Madrid, Spain; Ingrid Pinel, Faculty of Applied Sciences, Delft University, Delft, Netherlands.

                Citation Loveridge EJ, Jones C, Bull MJ, Moody SC, Kahl MW, Khan Z, Neilson L, Tomeva M, Adams SE, Wood AC, Rodriguez-Martin D, Pinel I, Parkhill J, Mahenthiralingam E, Crosby J. 2017. Reclassification of the specialized metabolite producer Pseudomonas mesoacidophila ATCC 31433 as a member of the Burkholderia cepacia complex. J Bacteriol 199:e00125-17. https://doi.org/10.1128/JB.00125-17.

                Author information
                http://orcid.org/0000-0002-8528-4019
                http://orcid.org/0000-0001-6275-0235
                http://orcid.org/0000-0002-7069-5958
                http://orcid.org/0000-0001-9014-3790
                Article
                00125-17
                10.1128/JB.00125-17
                5472815
                28439036
                f0e745a9-2561-4e61-9c73-c95b07b43ab9
                Copyright © 2017 Loveridge et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 1 March 2017
                : 13 April 2017
                Page count
                Figures: 3, Tables: 4, Equations: 0, References: 54, Pages: 12, Words: 6928
                Funding
                Funded by: Life Science Research Network Wales
                Award ID: NRNSep14036
                Award Recipient : E. Joel Loveridge
                Funded by: Biochemical Society https://doi.org/10.13039/501100000373
                Award Recipient : E. Joel Loveridge
                Funded by: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) https://doi.org/10.13039/501100000268
                Award ID: BB/L01758X/1
                Award Recipient : E. Joel Loveridge
                Funded by: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) https://doi.org/10.13039/501100000268
                Award ID: BB/L021692/1
                Award Recipient : Julian Parkhill Award Recipient : Eshwar Mahenthiralingam
                Funded by: RCUK | Medical Research Council (MRC) https://doi.org/10.13039/501100000265
                Award ID: MR/L015080/1
                Award Recipient : Matthew J. Bull
                Categories
                Research Article
                Custom metadata
                July 2017

                Microbiology & Virology
                genome,identification,antibiotic resistance,metal resistance,antibacterial,biosynthesis,bulgecin

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