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Enrichment, Isolation and Characterization of Phenazine-1-Carboxylic Acid (PCA)-Degrading Bacteria Under Aerobic and Anaerobic Conditions

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Enrichment, Isolation and Characterization of Phenazine-1-Carboxylic Acid (PCA)-Degrading Bacteria Under Aerobic and Anaerobic Conditions Enrichment, isolation and characterization of phenazine-1-carboxylic acid (PCA)-degrading bacteria under aerobic and anaerobic conditions Miaomiao Zhang A thesis in fulfilment of the requirements for the degree of Doctor of Philosophy School of Civil and Environmental Engineering Faculty of Engineering September, 2018 THE UNIVERSITY OF NEW SOUTH WALES Thesis/Dissertation Sheet Surname or Family name: ZHANG First name: Miaomiao Other name/s: Abbreviation for degree as given in the University calendar: PhD School: Civil and Environmental Engineering Faculty: Engineering Title: Enrichment, isolation and characterization of phenazine-1- carboxylic acid (PCA)-degrading bacteria under aerobic and anaerobic conditions Abstract Phenazines are a large class of nitrogen-containing aromatic heterocyclic compounds produced and secreted by bacteria from phylogenetically diverse taxa under aerobic and anaerobic conditions. Phenazine-1-carboxylic acid (PCA) is regarded as a ‘core’ phenazine because it is transformed to other phenazine derivatives. Due to their important roles in ecological fitness, biocontrol of plant pathogens, infection in cystic fibrosis and potential in anticancer treatments, understanding the fate of phenazine compounds is prudent. Only seven bacterial species are known to degrade phenazines and all of them are aerobic. Hence, the aim of this study is to enrich, isolate and characterize additional bacteria with the ability to degrade phenazines aerobically and anaerobically. In this study, the isolation of a PCA-degrading Rhodanobacter sp. PCA2 belonging to Grammaproteobacteria is reported. Characterization studies revealed that strain PCA2 is also capable of transforming other phenazines including phenazine, pyocyanin and 1-hydroxyphenazine. The sequencing, annotation and analysis of the genome of strain PCA2 revealed that genes (ubiD and the homolog of the MFORT_16269 gene) involved in PCA degradation were plasmid borne. Studies on abundance and expression of the homolog of MFORT_16269 gene via qPCR and RT-qPCR showed its involvement in PCA degradation by strain PCA2. Furthermore, results from LC-MS analysis together with proteomics indicated that strain PCA2 degraded PCA via decarboxylation and cleavage of aromatic and nitrogen-containing rings, potentially catalysed by UbiD, UbiX, phenylpropionate dioxygenase, biphenyl-2,3-diol 1,2-dioxygenase, amidohydrolase and nitroreductase. Three intermediates including phenazine, (4Z)-2-hydroxy-5- {[(1Z)-6-(hydroxyamino)cyclohexa -2,4-dien-1-ylidene]carbamoyl} penta-2,4-dienoic acid (HCCPD) and phenylhydroxylamine are reported. This study also reports the isolation of the first known anaerobic PCA degrading bacterium. Enterobacteriaceae were highly enriched after anaerobic incubation with PCA as a carbon, nitrogen and energy source and iron(III) as a terminal electron acceptor. Ultimately a Morganella morganii strain was isolated and shown to oxidise PCA whilst reducing iron(III). Declaration relating to disposition of project thesis/dissertation I hereby grant to the University of New South Wales or its agents the right to archive and to make available my thesis or dissertation in whole or in part in the University libraries in all forms of media, now or here after known, subject to the provisions of the Copyright Act 1968. I retain all property rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertation. I also authorise University Microfilms to use the 350 word abstract of my thesis in Dissertation Abstracts International (this is applicable to doctoral theses only).e 29/06/2018 ………………………………..…… ……………………………………..…… ……….……………………....… Signature Witness Signature Date The University recognises that there may be exceptional circumstances requiring restrictions on copying or conditions on use. Requests for restriction for a period of up to 2 years must be made in writing. Requests for a longer period of restriction may be considered in exceptional circumstances and require the approval of the Dean of Graduate Research. FOR OFFICE USE ONLY Date of completion of requirements for Award: Abstract Phenazines are a large class of nitrogen-containing aromatic heterocyclic compounds produced and secreted by bacteria from phylogenetically diverse taxa under aerobic and anaerobic conditions. Phenazine-1-carboxylic acid (PCA) is regarded as a ‘core’ phenazine because it is transformed to other phenazine derivatives. Due to their important roles in ecological fitness, biocontrol of plant pathogens, infection in cystic fibrosis and potential in anticancer treatments, understanding the fate of phenazine compounds is prudent. Only seven bacterial species are known to degrade phenazines and all of them are aerobic. Hence, the aim of this study is to enrich, isolate and characterize additional bacteria with the ability to degrade phenazines aerobically and anaerobically. In this study, the isolation of a PCA-degrading Rhodanobacter sp. PCA2 belonging to Grammaproteobacteria is reported. Characterization studies revealed that strain PCA2 is also capable of transforming other phenazines including phenazine, pyocyanin and 1- hydroxyphenazine. The sequencing, annotation and analysis of the genome of strain PCA2 revealed that genes (ubiD and the homolog of the MFORT_16269 gene) involved in PCA degradation were plasmid borne. Studies on abundance and expression of the homolog of MFORT_16269 gene via qPCR and RT-qPCR showed its involvement in PCA degradation by strain PCA2. Furthermore, results from LC-MS analysis together with proteomics indicated that strain PCA2 degraded PCA via decarboxylation and cleavage of aromatic and nitrogen-containing rings, potentially catalysed by UbiD, UbiX, phenylpropionate dioxygenase, biphenyl-2,3-diol 1,2-dioxygenase, amidohydrolase and nitroreductase. Three intermediates including phenazine, (4Z)-2- hydroxy-5-{[(1Z)-6-(hydroxyamino)cyclohexa -2,4-dien-1-ylidene]carbamoyl} penta- 2,4-dienoic acid (HCCPD) and phenylhydroxylamine are reported. This study also reports the isolation of the first known anaerobic PCA degrading bacterium. Enterobacteriaceae were highly enriched after anaerobic incubation with PCA as a carbon, nitrogen and energy source and iron(III) as a terminal electron acceptor. Ultimately a Morganella morganii strain was isolated and shown to oxidise PCA whilst reducing iron(III). I ORIGINALITY STATEMENT ‘I hereby declare that this submission is my own work and to the best of my knowledge it contains no materials previously published or written by another person, or substantial proportions of material which have been accepted for the award of any other degree or diploma at UNSW or any other educational institution, except where due acknowledgement is made in the thesis. Any contribution made to the research by others, with whom I have worked at UNSW or elsewhere, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project's design and conception or in style, presentation and linguistic expression is acknowledged.’ Signed …………………………………………….............. 29/06/2018 Date …………………………………… ……….............. II COPYRIGHT STATEMENT ‘I hereby grant the University of New South Wales or its agents the right to archive and to make available my thesis or dissertation in whole or part in the University libraries in all forms of media, now or here after known, subject to the provisions of the Copyright Act 1968. I retain all proprietary rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertation. I also authorise University Microfilms to use the 350 word abstract of my thesis in Dissertation Abstract International (this is applicable to doctoral theses only). I have either used no substantial portions of copyright material in my thesis or I have obtained permission to use copyright material; where permission has not been granted I have applied/will apply for a partial restriction of the digital copy of my thesis or dissertation.’ Signed ……………………………………………........................... 29/06/2018 Date ……………………………………...................................... AUTHENTICITY STATEMENT ‘I certify that the Library deposit digital copy is a direct equivalent of the final officially approved version of my thesis. No emendation of content has occurred and if there are any minor variations in formatting, they are the result of the conversion to digital format.’ Signed ……………………………………………........................... 29/06/2018 Date ……………………………………………........................... III Acknowledgements I would like to express my first and foremost thanks to my supervisor Prof. Mike Manefield for giving me the opportunity to work in his group, as well as for his great guidance and resources throughout the last few years. Thank you for providing me with the rewarding research experience to work towards and learn to be a professional scientist. Also, I must acknowledge him for allowing me the suitable degree of scientific freedom. My deepest appreciation goes out to you for your time and supervision that made my PhD study to be a professional and enjoyable journey. I would also like to take this chance to acknowledge Dr. Sabrina Beckmann for her continued guidance as a co-supervisor during my early half and two years and offering me opportunities to work on neutral red crystal. I am grateful
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