@article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/106810,
    title ="Bidirectional redox cycling of phenazine-1-carboxylic acid by Citrobacter portucalensis MBL drives increased nitrate reduction",
    author = "Tsypin, Lev M. and Newman, Dianne K.",
    
    
    
    
    month = "November",
    year = "2020",
    
    
    
    url = "https://resolver.caltech.edu/CaltechAUTHORS:20201124-104632686",
    note = "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nVersion 1 (November 24, 2020 - 08:09); this version posted November 25, 2020. \n\nWe would like to thank the members of the Newman lab, and especially Scott Saunders, Darcy McRose, Avi Flamholz, John Ciemniecki, Chelsey VanDrisse, and Justin Bois for their insight and helpful discussions throughout this work. We are grateful to Nathan Dalleska at the Environmental Analysis Center at Caltech for training LMT on the Dionex instrument and providing a facility for analytical chemistry. LMT was supported by the Rosen Endowment Fellowship at Caltech and the National Science Foundation Graduate Research Fellowship\n(DGE‐1745301). Additional support to DKN came from NIH (1R01AI127850-01A1 and 1R01HL152190-01) and ARO (W911NF-17-1-0024) grants.",
    revision_no = "20",
    abstract = "Phenazines are secreted metabolites that microbes use in diverse ways, from quorum sensing to antimicrobial warfare to energy conservation. Phenazines are able to contribute to these activities due to their redox activity. The physiological consequences of cellular phenazine reduction have been extensively studied, but the counterpart phenazine oxidation has been largely overlooked. Phenazine-1-carboxylic acid (PCA) is common in the environment and readily reduced by its producers. Here, we describe its anaerobic oxidation by Citrobacter portucalensis strain MBL, which was isolated from topsoil in Falmouth, MA, and which does not produce phenazines itself. This activity depends on the availability of a suitable terminal electron acceptor, specifically nitrate or fumarate. When C. portucalensis MBL is provided reduced PCA and either nitrate or fumarate, it continuously oxidizes the PCA. We compared this terminal electron acceptor-dependent PCA-oxidizing activity of C. portucalensis MBL to that of several other γ-proteobacteria with varying capacities to respire nitrate and/or fumarate. We found that PCA oxidation by these strains in a fumarate-or nitrate-dependent manner is decoupled from growth and correlated with their possession of the fumarate or periplasmic nitrate reductases, respectively. We infer that bacterial PCA oxidation is widespread and genetically determined. Notably, reduced PCA enhances the rate of nitrate reduction to nitrite by C. portucalensis MBL beyond the stoichiometric prediction, which we attribute to C. portucalensis MBL’s ability to also reduce oxidized PCA, thereby catalyzing a complete PCA redox cycle. This bidirectionality highlights the versatility of PCA as a biological redox agent.",
}
@article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/102703,
    title ="Bacterial defenses against a natural antibiotic promote collateral resilience to clinical antibiotics",
    author = "Meirelles, Lucas A. and Perry, Elena K.",
    
    
    
    
    month = "April",
    year = "2020",
    
    
    
    url = "https://resolver.caltech.edu/CaltechAUTHORS:20200421-132753787",
    note = "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nPosted April 20, 2020. \n\nWe thank members of the Newman lab and Shashank Gandhi for constructive feedback throughout the project and on the manuscript. We also thank Steven Wilbert for assistance with image analysis, David Basta for providing the plasmid used for lptA deletion, and The Millard and Muriel Jacobs Genetics and Genomics Laboratory at Caltech and Igor Antoshechkin for support during library preparation and sequencing of the Tn-seq samples. Finally, we thank John LiPuma (CFF Burkholderia cepacia Research Laboratory and Repository at the University of Michigan) for providing clinical Burkholderia strains. Grants to D.K.N. from the NIH (1R01AI127850-01A1) and ARO (W911NF-17-1-0024) supported this work. E.K.P. was supported by a National Science Foundation Graduate Research Fellowship under Grant No. DGE-1745301. \n\nAuthor contributions: These authors contributed equally and are listed alphabetically: Lucas A. Meirelles and Elena K. Perry. Study conception: L.A.M., E.K.P., D.K.N. Study design: L.A.M., E.K.P., M.B., D.K.N. Tn-seq: L.A.M, M.B. Tolerance experiments: L.A.M. Resistance experiments: E.K.P. Manuscript preparation: E.K.P., L.A.M., M.B., D.K.N. Study supervision and funding: D.K.N. \n\nThe authors declare no competing interests. \n\nData and materials availability: Tn-seq data have been deposited at GEO under accession number GSE148769. Whole genome sequencing data for Δphz and ciprofloxacin-resistant mutants of P. aeruginosa and B. multivorans AU42096 have been deposited at NCBI under accession number PRJNA625945. All other data that support the findings of this study are available from the corresponding author upon reasonable request.",
    revision_no = "21",
    abstract = "As antibiotic-resistant infections become increasingly prevalent worldwide, understanding the factors that lead to antimicrobial treatment failure is essential to optimizing the use of existing drugs. Opportunistic human pathogens in particular typically exhibit high levels of intrinsic antibiotic resistance and tolerance1, leading to chronic infections that can be nearly impossible to eradicate2. We asked whether the recalcitrance of these organisms to antibiotic treatment could be driven in part by their evolutionary history as environmental microbes, which frequently produce or encounter natural antibiotics3,4. Using the opportunistic pathogen Pseudomonas aeruginosa as a model, we demonstrate that the self-produced natural antibiotic pyocyanin (PYO) activates bacterial defenses that confer collateral tolerance to certain synthetic antibiotics, including in a clinically-relevant growth medium. Non-PYO-producing opportunistic pathogens isolated from lung infections similarly display increased antibiotic tolerance when they are co-cultured with PYO-producing P. aeruginosa. Furthermore, we show that beyond promoting bacterial survival in the presence of antibiotics, PYO can increase the apparent rate of mutation to antibiotic resistance by up to two orders of magnitude. Our work thus suggests that bacterial production of natural antibiotics in infections could play an important role in modulating not only the immediate efficacy of clinical antibiotics, but also the rate at which antibiotic resistance arises in multispecies bacterial communities.",
}
@article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/90009,
    title ="Extended hopanoid lipids promote bacterial motility, surface attachment, and root nodule development in the Bradyrhizobium diazoefficiens-Aeschynomene afraspera symbiosis",
    author = "Belin, Brittany J. and Tookmanian, Elise T.",
    
    
    
    
    month = "September",
    year = "2018",
    
    
    
    url = "https://resolver.caltech.edu/CaltechAUTHORS:20180927-114224832",
    note = "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. \n\nThis work was supported by grants from the HHMI (D.K.N.), NASA (NNX12AD93G, D.K.N.), Jane Coffin Childs Memorial Fund (B.J.B.), NIH (K99GM126141, B.J.B.), and Ford Foundation Predoctoral Fellowship (J.d.A.), and Army Research Office (W911NF-18-1-0254, GW). We thank Dr. Eric Giraud for his generous gift of A. afraspera seeds and training on Aeschynomene symbioses and Drs. Hans-Martin Fischer and Raphael Ledermann for plasmids and technical advice for the genetic transformation of B. diazoefficiens. Dr. Nathan Dalleska of the Environmental Analysis Center at Caltech was instrumental in providing training and support for GC-MS analysis of acetylene reduction. We are grateful to Dr. Gargi Kulkarni and other members of the Newman lab, as well as Drs. Elliot Meyerowitz and Rob Phillips, for their collegiality and thoughtful discussions about this work. We are indebted to Ms. Shannon Park and Ms. Kristy Nguyen for providing the administrative assistance that allows us to focus on our research.",
    revision_no = "15",
    abstract = "Hopanoids are steroid-like bacterial lipids that enhance membrane rigidity and promote bacterial growth under diverse stresses. Roughly 10% of bacteria contain genes involved in hopanoid biosynthesis, and these genes are particularly conserved in plant-associated organisms. We previously found that the extended class of hopanoids (C35) in the nitrogen-fixing soil bacterium Bradyrhizobium diazoefficiens promotes its root nodule symbiosis with the tropical legume Aeschynomene afraspera. By quantitatively modeling root nodule development, we identify independent roles for hopanoids in the initiation of root nodule formation and in determining the rate of root nodule maturation. In vitro studies demonstrate that extended hopanoids support B. diazoefficiens motility and surface attachment, which may correlate with stable root colonization in planta. Confocal microscopy of maturing root nodules reveals that root nodules infected with extended hopanoid-deficient B. diazoefficiens contain unusually low densities of bacterial symbionts, indicating that extended hopanoids are necessary for persistent, high levels of host infection. This work identifies extended hopanoids as regulators of the efficiency of Bradyrhizobia nitrogen-fixing symbioses, agriculturally and economically significant associations with growing importance in a changing climate.",
}