A Chemical-Genomic Screen of Neglected Antibiotics Reveals Illicit Transport of Kasugamycin and Blasticidin S

Shiver, Anthony L.; Osadnik, Hendrik; Kritikos, George; Li, Bo; Krogan, Nevan; Typas, Athanasios; Gross, Carol A.; Hughes, ed., Diarmaid

doi:10.1371/journal.pgen.1006124

Title: A Chemical-Genomic Screen of Neglected Antibiotics Reveals Illicit Transport of Kasugamycin and Blasticidin S

Journal Article · Wed Jun 29 00:00:00 EDT 2016 · PLoS Genetics

DOI:https://doi.org/10.1371/journal.pgen.1006124· OSTI ID:1337762

Shiver, Anthony L.;

; Kritikos, George; Li, Bo; Krogan, Nevan; Typas, Athanasios;

; Hughes, ed., Diarmaid

Fighting antibiotic resistance requires a deeper understanding of the genetic factors that determine the antibiotic susceptibility of bacteria. Here we describe a chemical-genomic screen in Escherichia coli K-12 that was designed to discover new aspects of antibiotic resistance by focusing on a set of 26 antibiotics and other stresses with poorly characterized mode-of-action and determinants of resistance. We show that the screen identifies new resistance determinants for these antibiotics including a common signature from two antimicrobials, kasugamycin and blasticidin S, used to treat crop diseases like rice blast and fire blight. Following this signature, we further investigated the mechanistic basis for susceptibility to kasugamycin and blasticidin S in E. coli using both genetic and biochemical approaches. We provide evidence that these compounds hijack an overlapping set of peptide ABC-importers to enter the bacterial cell. As a result, the loss of uptake may be an underappreciated mechanism for the development of kasugamycin resistance in bacterial plant pathogens.

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Research Organization:: Office of Scientific and Technical Information, Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: Graduate Fellowship

OSTI ID:: 1337762

Alternate ID(s):: OSTI ID: 1376695

Journal Information:: PLoS Genetics, Journal Name: PLoS Genetics Vol. 12 Journal Issue: 6; ISSN 1553-7404

Publisher:: Public Library of Science (PLoS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 28 works

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References (62)

Single-Gene Deletion Mutants of Escherichia coli with Altered Sensitivity to Bicyclomycin, an Inhibitor of Transcription Termination Factor Rho Tran, L.; van Baarsel, J. A.; Washburn, R. S. Journal of Bacteriology, Vol. 193, Issue 9 https://doi.org/10.1128/JB.01463-10	journal	February 2011
Identification of Three Different Loci Controlling Kasugamycin Resistance in Pyricularia oryzae Taga, M. Phytopathology, Vol. 69, Issue 5 https://doi.org/10.1094/Phyto-69-463	journal	January 1979
A strategy for extracting and analyzing large-scale quantitative epistatic interaction data Collins, Sean R.; Schuldiner, Maya; Krogan, Nevan J. Genome Biology, Vol. 7, Issue 7, p. R63 https://doi.org/10.1186/gb-2006-7-7-r63	journal	January 2006
The crystal structures of the oligopeptide-binding protein OppA complexed with tripeptide and tetrapeptide ligands Tame, Jeremy RH; Dodson, Eleanor J.; Murshudov, Garib Structure, Vol. 3, Issue 12 https://doi.org/10.1016/S0969-2126(01)00276-3	journal	December 1995
Ligand binding assays at equilibrium: validation and interpretation: Equilibrium binding assays Hulme, Edward C.; Trevethick, Mike A. British Journal of Pharmacology, Vol. 161, Issue 6 https://doi.org/10.1111/j.1476-5381.2009.00604.x	journal	February 2010
Open source clustering software de Hoon, M. J. L.; Imoto, S.; Nolan, J. Bioinformatics, Vol. 20, Issue 9 https://doi.org/10.1093/bioinformatics/bth078	journal	February 2004
ABC Taansporter Genes, kasKLM, Responsible for Self-resistance of a Kasugamycin Producer Strain. Ikeno, Souichi; Yamane, Yasuhiro; Ohishi, Yoko The Journal of Antibiotics, Vol. 53, Issue 4 https://doi.org/10.7164/antibiotics.53.373	journal	January 2000
The housekeeping dipeptide permease is the Escherichia coli heme transporter and functions with two optional peptide binding proteins Letoffe, S.; Delepelaire, P.; Wandersman, C. Proceedings of the National Academy of Sciences, Vol. 103, Issue 34 https://doi.org/10.1073/pnas.0605440103	journal	August 2006
Coordination of peptidoglycan synthesis and outer membrane constriction during Escherichia coli cell division Gray, Andrew N.; Egan, Alexander JF; van't Veer, Inge L. eLife, Vol. 4 https://doi.org/10.7554/eLife.07118	journal	May 2015
Two periplasmic transport proteins which interact with a common membrane receptor show extensive homology: complete nucleotide sequences. Higgins, C. F.; Ames, G. F. Proceedings of the National Academy of Sciences, Vol. 78, Issue 10 https://doi.org/10.1073/pnas.78.10.6038	journal	October 1981
Genome-Wide Screening with Hydroxyurea Reveals a Link between Nonessential Ribosomal Proteins and Reactive Oxygen Species Production Nakayashiki, T.; Mori, H. Journal of Bacteriology, Vol. 195, Issue 6 https://doi.org/10.1128/JB.02145-12	journal	January 2013
MppA, a Periplasmic Binding Protein Essential for Import of the Bacterial Cell Wall Peptidel-Alanyl-γ-d-Glutamyl-meso-Diaminopimelate Park, James T.; Raychaudhuri, Debabrata; Li, Hongshan Journal of Bacteriology, Vol. 180, Issue 5 https://doi.org/10.1128/JB.180.5.1215-1223.1998	journal	March 1998
Determination of Antibiotic Hypersensitivity among 4,000 Single-Gene-Knockout Mutants of Escherichia coli Tamae, C.; Liu, A.; Kim, K. Journal of Bacteriology, Vol. 190, Issue 17 https://doi.org/10.1128/JB.01982-07	journal	July 2008
Regulation of Peptidoglycan Synthesis by Outer-Membrane Proteins Typas, Athanasios; Banzhaf, Manuel; van den Berg van Saparoea, Bart Cell, Vol. 143, Issue 7 https://doi.org/10.1016/j.cell.2010.11.038	journal	December 2010
STRUCTURE AND FUNCTION OF E. coli RIBOSOMES, VIII. COLD-SENSITIVE MUTANTS DEFECTIVE IN RIBOSOME ASSEMBLY Guthrie, C.; Nashimoto, H.; Nomura, M. Proceedings of the National Academy of Sciences, Vol. 63, Issue 2 https://doi.org/10.1073/pnas.63.2.384	journal	June 1969
A Genome-Wide Screen for Bacterial Envelope Biogenesis Mutants Identifies a Novel Factor Involved in Cell Wall Precursor Metabolism Paradis-Bleau, Catherine; Kritikos, George; Orlova, Katya PLoS Genetics, Vol. 10, Issue 1 https://doi.org/10.1371/journal.pgen.1004056	journal	January 2014
Evaluation of Kasugamycin for Fire Blight Management, Effect on Nontarget Bacteria, and Assessment of Kasugamycin Resistance Potential in Erwinia amylovora McGhee, Gayle C.; Sundin, George W. Phytopathology, Vol. 101, Issue 2 https://doi.org/10.1094/PHYTO-04-10-0128	journal	February 2011
A structural classification of substrate-binding proteins Berntsson, Ronnie P. -A.; Smits, Sander H. J.; Schmitt, Lutz FEBS Letters, Vol. 584, Issue 12 https://doi.org/10.1016/j.febslet.2010.04.043	journal	April 2010
Acquired Tolerance to Blasticidin-S in Pyricularia oryzae Hwang, Byung Kook Phytopathology, Vol. 77, Issue 3 https://doi.org/10.1094/Phyto-67-421	journal	January 1977
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles Subramanian, A.; Tamayo, P.; Mootha, V. K. Proceedings of the National Academy of Sciences, Vol. 102, Issue 43, p. 15545-15550 https://doi.org/10.1073/pnas.0506580102	journal	September 2005
Peptide Transport and Metabolism in Bacteria Sussman, A. J.; Gilvarg, C. Annual Review of Biochemistry, Vol. 40, Issue 1 https://doi.org/10.1146/annurev.bi.40.070171.002145	journal	June 1971
Peptide transport and chemotaxis in Escherichia coli and Salmonella typhimurium: characterization of the dipeptide permease (Dpp) and the dipeptide-binding protein Abouhamad, W. N.; Manson, M.; Gibson, M. M. Molecular Microbiology, Vol. 5, Issue 5 https://doi.org/10.1111/j.1365-2958.1991.tb01876.x	journal	May 1991
Specificity and interactions of the protein OppA: partitioning solvent binding effects using mass spectrometry 1 1Edited by P. E. Wright Rostom, Adam A.; Tame, Jeremy R. H.; Ladbury, John E. Journal of Molecular Biology, Vol. 296, Issue 1 https://doi.org/10.1006/jmbi.1999.3431	journal	February 2000
Substrate specificity of the periplasmic dipeptide-binding protein from Escherichia coli: experimental basis for the design of peptide prodrugs Payne, John W.; Payne, Gillian M.; Marshall, Neil J. Microbiology, Vol. 145, Issue 10 https://doi.org/10.1099/00221287-145-10-2891	journal	October 1999
The Escherichia coli protein YjjG is a house-cleaning nucleotidase in vivo Titz, BjÃ¶rn; HÃ¤user, Roman; Engelbrecher, Anne FEMS Microbiology Letters, Vol. 270, Issue 1 https://doi.org/10.1111/j.1574-6968.2007.00646.x	journal	May 2007
NorM, a Putative Multidrug Efflux Protein, of Vibrio parahaemolyticus and Its Homolog in Escherichia coli Morita, Yuji; Kodama, Kazuyo; Shiota, Sumiko Antimicrobial Agents and Chemotherapy, Vol. 42, Issue 7 https://doi.org/10.1128/AAC.42.7.1778	journal	July 1998
Antibiotic Sensitivity Profiles Determined with an Escherichia coli Gene Knockout Collection: Generating an Antibiotic Bar Code Liu, A.; Tran, L.; Becket, E. Antimicrobial Agents and Chemotherapy, Vol. 54, Issue 4 https://doi.org/10.1128/AAC.00906-09	journal	January 2010
The Complete Genome Sequence of Escherichia coli K-12 Blattner, F. R. Science, Vol. 277, Issue 5331 https://doi.org/10.1126/science.277.5331.1453	journal	September 1997
Targeting a bacterial stress response to enhance antibiotic action Lee, S.; Hinz, A.; Bauerle, E. Proceedings of the National Academy of Sciences, Vol. 106, Issue 34 https://doi.org/10.1073/pnas.0903619106	journal	August 2009
Synthesis of Guanosine Tetra- and Pentaphosphate Requires the Presence of a Codon-Specific, Uncharged Transfer Ribonucleic Acid in the Acceptor Site of Ribosomes Haseltine, W. A.; Block, R. Proceedings of the National Academy of Sciences, Vol. 70, Issue 5, p. 1564-1568 https://doi.org/10.1073/pnas.70.5.1564	journal	May 1973
Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. Guzman, L. M.; Belin, D.; Carson, M. J. Journal of Bacteriology, Vol. 177, Issue 14, p. 4121-4130 https://doi.org/10.1128/jb.177.14.4121-4130.1995	journal	July 1995
MicL, a new E-dependent sRNA, combats envelope stress by repressing synthesis of Lpp, the major outer membrane lipoprotein Guo, M. S.; Updegrove, T. B.; Gogol, E. B. Genes & Development, Vol. 28, Issue 14 https://doi.org/10.1101/gad.243485.114	journal	July 2014
Expanded microbial genome coverage and improved protein family annotation in the COG database Galperin, Michael Y.; Makarova, Kira S.; Wolf, Yuri I. Nucleic Acids Research, Vol. 43, Issue D1 https://doi.org/10.1093/nar/gku1223	journal	November 2014
Widespread Genetic Switches and Toxicity Resistance Proteins for Fluoride Baker, J. L.; Sudarsan, N.; Weinberg, Z. Science, Vol. 335, Issue 6065 https://doi.org/10.1126/science.1215063	journal	December 2011
opp-lac Operon fusions and transcriptional regulation of the Escherichia coli trp-linked oligopeptide permease. Andrews, J. C.; Short, S. A. Journal of Bacteriology, Vol. 165, Issue 2 https://doi.org/10.1128/jb.165.2.434-442.1986	journal	February 1986
Complete Genome Sequence of Escherichia coli BW25113 Grenier, F.; Matteau, D.; Baby, V. Genome Announcements, Vol. 2, Issue 5 https://doi.org/10.1128/genomeA.01038-14	journal	September 2014
Escherichia coli Peptide Binding Protein OppA Has a Preference for Positively Charged Peptides Klepsch, M. M.; Kovermann, M.; Löw, C. Journal of Molecular Biology, Vol. 414, Issue 1 https://doi.org/10.1016/j.jmb.2011.09.043	journal	November 2011
Experimental and Computational Assessment of Conditionally Essential Genes in Escherichia coli Joyce, A. R.; Reed, J. L.; White, A. Journal of Bacteriology, Vol. 188, Issue 23 https://doi.org/10.1128/JB.00740-06	journal	September 2006
The Escherichia coli Yej Transporter Is Required for the Uptake of Translation Inhibitor Microcin C Novikova, M.; Metlitskaya, A.; Datsenko, K. Journal of Bacteriology, Vol. 189, Issue 22 https://doi.org/10.1128/JB.01028-07	journal	September 2007
Blast from the Past: Reassessing Forgotten Translation Inhibitors, Antibiotic Selectivity, and Resistance Mechanisms to Aid Drug Development Arenz, Stefan; Wilson, Daniel N. Molecular Cell, Vol. 61, Issue 1 https://doi.org/10.1016/j.molcel.2015.10.019	journal	January 2016
The gcvB gene encodes a small untranslated RNA involved in expression of the dipeptide and oligopeptide transport systems in Escherichia coli Urbanowski, Mark L.; Stauffer, Lorraine T.; Stauffer, George V. Molecular Microbiology, Vol. 37, Issue 4 https://doi.org/10.1046/j.1365-2958.2000.02051.x	journal	August 2000
Rho and NusG suppress pervasive antisense transcription in Escherichia coli Peters, J. M.; Mooney, R. A.; Grass, J. A. Genes & Development, Vol. 26, Issue 23 https://doi.org/10.1101/gad.196741.112	journal	December 2012
Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America Boucher, Helen W.; Talbot, George H.; Bradley, John S. Clinical Infectious Diseases, Vol. 48, Issue 1 https://doi.org/10.1086/595011	journal	January 2009
A Pyranose-2-Phosphate Motif Is Responsible for Both Antibiotic Import and Quorum-Sensing Regulation in Agrobacterium tumefaciens El Sahili, Abbas; Li, Si-Zhe; Lang, Julien PLOS Pathogens, Vol. 11, Issue 8 https://doi.org/10.1371/journal.ppat.1005071	journal	August 2015
Periplasmic protein associated with the oligopeptide permeases of Salmonella typhimurium and Escherichia coli. Higgins, C. F.; Hardie, M. M. Journal of Bacteriology, Vol. 155, Issue 3 https://doi.org/10.1128/JB.155.3.1434-1438.1983	journal	January 1983
Phenotypic Landscape of a Bacterial Cell Nichols, Robert J.; Sen, Saunak; Choo, Yoe Jin Cell, Vol. 144, Issue 1 https://doi.org/10.1016/j.cell.2010.11.052	journal	January 2011
Peptide chemotaxis in E. coli involves the Tap signal transducer and the dipeptide permease Manson, Michael D.; Blank, Volker; Brade, Gabriele Nature, Vol. 321, Issue 6067 https://doi.org/10.1038/321253a0	journal	May 1986
Illicit Transport via Dipeptide Transporter Dpp is Irrelevant to the Efficacy of Negamycin in Mouse Thigh Models of Escherichia coli Infection McKinney, David C.; Bezdenejnih-Snyder, Natascha; Farrington, Krista ACS Infectious Diseases, Vol. 1, Issue 5 https://doi.org/10.1021/acsinfecdis.5b00027	journal	April 2015
Java Treeview--extensible visualization of microarray data Saldanha, A. J. Bioinformatics, Vol. 20, Issue 17 https://doi.org/10.1093/bioinformatics/bth349	journal	June 2004
Crystallographic and Calorimetric Analysis of Peptide Binding to OppA Protein Sleigh, S. H.; Seavers, P. R.; Wilkinson, A. J. Journal of Molecular Biology, Vol. 291, Issue 2 https://doi.org/10.1006/jmbi.1999.2929	journal	August 1999
Membrane Proteases and Aminoglycoside Antibiotic Resistance Hinz, A.; Lee, S.; Jacoby, K. Journal of Bacteriology, Vol. 193, Issue 18 https://doi.org/10.1128/JB.05133-11	journal	July 2011
Binding specificity of the periplasmic oligopeptide-binding protein from Escherichia coli. Guyer, C. A.; Morgan, D. G.; Staros, J. V. Journal of Bacteriology, Vol. 168, Issue 2 https://doi.org/10.1128/jb.168.2.775-779.1986	journal	November 1986
Multidrug efflux pumps of gram-negative bacteria. Nikaido, H. Journal of Bacteriology, Vol. 178, Issue 20 https://doi.org/10.1128/jb.178.20.5853-5859.1996	journal	October 1996
Illicit Transport: The Oligopeptide Permease Ames, B. N.; Ames, G. F. -L.; Young, J. D. Proceedings of the National Academy of Sciences, Vol. 70, Issue 2 https://doi.org/10.1073/pnas.70.2.456	journal	February 1973
Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions Cox, Georgina; Wright, Gerard D. International Journal of Medical Microbiology, Vol. 303, Issue 6-7 https://doi.org/10.1016/j.ijmm.2013.02.009	journal	August 2013
The Novel Kasugamycin 2′- N -Acetyltransferase Gene aac(2′)-IIa , Carried by the IncP Island, Confers Kasugamycin Resistance to Rice-Pathogenic Bacteria Yoshii, Atsushi; Moriyama, Hiromitsu; Fukuhara, Toshiyuki Applied and Environmental Microbiology, Vol. 78, Issue 16 https://doi.org/10.1128/AEM.01155-12	journal	June 2012
PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes Mootha, Vamsi K.; Lindgren, Cecilia M.; Eriksson, Karl-Fredrik Nature Genetics, Vol. 34, Issue 3 https://doi.org/10.1038/ng1180	journal	June 2003
Central role for RNase YbeY in Hfq-dependent and Hfq-independent small-RNA regulation in bacteria Pandey, Shree P.; Winkler, Jonathan A.; Li, Hu BMC Genomics, Vol. 15, Issue 1 https://doi.org/10.1186/1471-2164-15-121	journal	January 2014
The Pseudomonas aeruginosa PA14 ABC Transporter NppA1A2BCD Is Required for Uptake of Peptidyl Nucleoside Antibiotics Pletzer, Daniel; Braun, Yvonne; Dubiley, Svetlana Journal of Bacteriology, Vol. 197, Issue 13 https://doi.org/10.1128/JB.00234-15	journal	April 2015
Size Restriction on Peptide Utilization in Escherichia coli Payne, J. W.; Gilvarg, C. Journal of Biological Chemistry, Vol. 243, Issue 23 https://doi.org/10.1016/S0021-9258(18)94490-X	journal	December 1968
A cross-resistance of Pyricularia oryzae Cavara to kasugamycin and blasticidin S. Sakurai, Hisashi; Naito, Hisashi The Journal of Antibiotics, Vol. 29, Issue 12 https://doi.org/10.7164/antibiotics.29.1341	journal	January 1976
Specificity Mutants of the Binding Protein of the Oligopeptide Transport System of Lactococcus lactis Picon, A.; Kunji, E. R. S.; Lanfermeijer, F. C. Journal of Bacteriology, Vol. 182, Issue 6 https://doi.org/10.1128/JB.182.6.1600-1608.2000	journal	March 2000

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