{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T09:48:28Z","timestamp":1768729708514,"version":"3.49.0"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003074","name":"ANPCyT","doi-asserted-by":"crossref","award":["PICT 2017-1627"],"award-info":[{"award-number":["PICT 2017-1627"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003074","name":"ANPCyT","doi-asserted-by":"crossref","award":["PICT 2017-2421"],"award-info":[{"award-number":["PICT 2017-2421"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003074","name":"ANPCyT","doi-asserted-by":"crossref","award":["PICT StartUp 2020-0035"],"award-info":[{"award-number":["PICT StartUp 2020-0035"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002923","name":"CONICET","doi-asserted-by":"crossref","award":["PUE-2016-CONICET-22920160100039CO"],"award-info":[{"award-number":["PUE-2016-CONICET-22920160100039CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The overprescription and misuse of classical antimicrobial compounds to treat gastrointestinal or systemic salmonellosis have been accelerating the surge of antibiotic-recalcitrant bacterial populations, posing a major public health challenge. Therefore, alternative therapeutic approaches to treat Salmonella infections are urgently required.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To identify and characterize actinobacterial secreted compounds with inhibitory properties against the Salmonella enterica PhoP\/PhoQ signal transduction system, crucial for virulence regulation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The methodology was based on a combination of the measurement of the activity of PhoP\/PhoQ-dependent and -independent reporter genes and bioguided assays to screen for bioactive inhibitory metabolites present in culture supernatants obtained from a collection of actinobacterial isolates. Analogues of azomycin were used to analyse the functional groups required for the detected bioactivity and Salmonella mutants and complemented strains helped to dissect the azomycin mechanism of action. The tetrazolium dye colorimetric assay was used to investigate azomycin potential cytotoxicity on cultured macrophages. Salmonella intramacrophage replication capacity upon azomycin treatment was assessed using the gentamicin protection assay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Sublethal concentrations of azomycin, a nitroheterocyclic compound naturally produced by Streptomyces eurocidicus, repressed the Salmonella PhoP\/PhoQ system activity by targeting PhoP and inhibiting its transcriptional activity in a PhoQ- and aspartate phosphorylation-independent manner. Sublethal, non-cytotoxic concentrations of azomycin prevented Salmonella intramacrophage replication.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Azomycin selectively inhibits the activity of the Salmonella virulence regulator PhoP, a new activity described for this nitroheterocyclic compound that can be repurposed to develop novel anti-Salmonella therapeutic approaches.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac278","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T12:27:58Z","timestamp":1660652878000},"page":"3050-3063","source":"Crossref","is-referenced-by-count":3,"title":["A natural product from <i>Streptomyces<\/i> targets PhoP and exerts antivirulence action against <i>Salmonella enterica<\/i>"],"prefix":"10.1093","volume":"77","author":[{"given":"Roberto E","family":"Bruna","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas, Universidad Nacional de Rosario, Rosario , Santa Fe , Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejo","family":"Casal","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas, Universidad Nacional de Rosario, Rosario , Santa Fe , Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara","family":"Bercovich","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas, Universidad Nacional de Rosario, Rosario , Santa Fe , Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"Gramajo","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas, Universidad Nacional de Rosario, Rosario , Santa Fe , Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas, Universidad Nacional de Rosario, Rosario , Santa Fe , Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4431-8606","authenticated-orcid":false,"given":"Eleonora","family":"Garc\u00eda V\u00e9scovi","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas, Universidad Nacional de Rosario, Rosario , Santa Fe , Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"2022102819180852300_dkac278-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5851\/kosfa.2020.e75","article-title":"Etiological agents implicated in foodborne illness world wide","volume":"41","author":"Lee","year":"2021","journal-title":"Food Sci Anim Resour"},{"key":"2022102819180852300_dkac278-B2","doi-asserted-by":"crossref","first-page":"e3394","DOI":"10.1371\/journal.pntd.0003394","article-title":"Invasive Salmonella Typhimurium ST313 with naturally attenuated flagellin elicits reduced inflammation and replicates within macrophages","volume":"9","author":"Ramachandran","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"2022102819180852300_dkac278-B3","doi-asserted-by":"crossref","first-page":"E2614","DOI":"10.1073\/pnas.1714718115","article-title":"Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella","volume":"115","author":"Hammarl\u00f6f","year":"2018","journal-title":"Proc Natl Acad Sci"},{"key":"2022102819180852300_dkac278-B4","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3390\/foods7100167","article-title":"Antibiotic-resistant Salmonella in the food supply and the potential role of antibiotic alternatives for control","volume":"7","author":"Nair","year":"2018","journal-title":"Foods"},{"key":"2022102819180852300_dkac278-B5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007948","article-title":"The fitness landscape of the African Salmonella Typhimurium ST313 strain D23580 reveals unique properties of the pBT1 plasmid","volume":"15","author":"Canals","year":"2019","journal-title":"PLoS Pathog"},{"key":"2022102819180852300_dkac278-B6","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/S1473-3099(19)30418-9","article-title":"The global burden of non-typhoidal Salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017","volume":"19","author":"Stanaway","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2022102819180852300_dkac278-B7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1086\/318457","article-title":"Nontyphoidal salmonellosis","volume":"32","author":"Hohmann","year":"2001","journal-title":"Clin Infect Dis"},{"key":"2022102819180852300_dkac278-B8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0950268802006842","article-title":"Salmonella surveillance: a global survey of public health serotyping","volume":"129","author":"Herikstad","year":"2002","journal-title":"Epidemiol Infect"},{"issue":"Suppl 14","key":"2022102819180852300_dkac278-B9","doi-asserted-by":"crossref","first-page":"E173","DOI":"10.2527\/jas.2007-0447","article-title":"Food animal-associated Salmonella challenges: pathogenicity and antimicrobial resistance","volume":"86","author":"Foley","year":"2008","journal-title":"J Anim Sci"},{"key":"2022102819180852300_dkac278-B10","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.meegid.2009.04.011","article-title":"Population structure, origins and evolution of major Salmonella enterica clones","volume":"9","author":"Lan","year":"2009","journal-title":"Infect Genet Evol"},{"key":"2022102819180852300_dkac278-B11","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1086\/650733","article-title":"The global burden of nontyphoidal Salmonella gastroenteritis","volume":"50","author":"Majowicz","year":"2010","journal-title":"Clin Infect Dis"},{"key":"2022102819180852300_dkac278-B12","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1089\/fpd.2010.0787","article-title":"Global monitoring of Salmonella serovar distribution from the World Health Organization Global Foodborne Infections Network Country Data Bank: results of quality assured laboratories from 2001 to 2007","volume":"8","author":"Hendriksen","year":"2011","journal-title":"Foodborne Pathog Dis"},{"key":"2022102819180852300_dkac278-B13","first-page":"299","article-title":"Antivirulence compounds: a future direction to overcome antibiotic resistance?","volume":"15","author":"Buroni","year":"2020","journal-title":"Futur Med"},{"key":"2022102819180852300_dkac278-B14","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2174\/1389450116666150806124110","article-title":"New antimicrobial approaches: reuse of old drugs","volume":"17","author":"Savoia","year":"2016","journal-title":"Curr Drug Targets"},{"key":"2022102819180852300_dkac278-B15","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41564-019-0357-1","article-title":"Drug repurposing for antimicrobial discovery","volume":"4","author":"Farha","year":"2019","journal-title":"Nat Microbiol"},{"key":"2022102819180852300_dkac278-B16","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81003-X","article-title":"Mg2+ as an extracellular signal: environmental regulation of Salmonella virulence","volume":"84","author":"V\u00e9scovi E","year":"1996","journal-title":"Cell"},{"key":"2022102819180852300_dkac278-B17","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1046\/j.1365-2958.2003.03675.x","article-title":"Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides","volume":"50","author":"Bader","year":"2003","journal-title":"Mol Microbiol"},{"key":"2022102819180852300_dkac278-B18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.cell.2005.05.030","article-title":"Recognition of antimicrobial peptides by a bacterial sensor kinase","volume":"122","author":"Bader","year":"2005","journal-title":"Cell"},{"key":"2022102819180852300_dkac278-B19","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.jmb.2005.12.032","article-title":"Metal bridges between the PhoQ sensor domain and the membrane regulate transmembrane signaling","volume":"356","author":"Cho","year":"2006","journal-title":"J Mol Biol"},{"key":"2022102819180852300_dkac278-B20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.molcel.2007.03.008","article-title":"Activation of the bacterial sensor kinase PhoQ by acidic pH","volume":"26","author":"Prost","year":"2007","journal-title":"Mol Cell"},{"key":"2022102819180852300_dkac278-B21","doi-asserted-by":"crossref","first-page":"22346","DOI":"10.1074\/jbc.M113.472829","article-title":"Unsaturated long chain free fatty acids are input signals of the Salmonella enterica PhoP\/PhoQ regulatory system","volume":"288","author":"Viarengo","year":"2013","journal-title":"J Biol Chem"},{"key":"2022102819180852300_dkac278-B22","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aaz3334","article-title":"PhoQ is an unsaturated fatty acid receptor that fine-tunes Salmonella pathogenic traits","volume":"13","author":"Carabajal","year":"2020","journal-title":"Sci Signal"},{"key":"2022102819180852300_dkac278-B23","doi-asserted-by":"crossref","first-page":"6287","DOI":"10.1128\/JB.185.21.6287-6294.2003","article-title":"Molecular characterization of the Mg2+-responsive PhoP-PhoQ regulon in Salmonella enterica","volume":"185","author":"Lejona","year":"2003","journal-title":"J Bacteriol"},{"key":"2022102819180852300_dkac278-B24","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1046\/j.1365-2958.2002.03017.x","article-title":"Novel mode of transcription regulation of divergently overlapping promoters by PhoP, the regulator of two-component system sensing external magnesium availability","volume":"45","author":"Yamamoto","year":"2002","journal-title":"Mol Microbiol"},{"key":"2022102819180852300_dkac278-B25","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1128\/JB.186.8.2476-2480.2004","article-title":"PhoP can activate its target genes in a PhoQ-independent manner","volume":"186","author":"Lejona","year":"2004","journal-title":"J Bacteriol"},{"key":"2022102819180852300_dkac278-B26","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1074\/jbc.M412741200","article-title":"Signal-dependent binding of the response regulators PhoP and PmrA to their target promoters in vivo","volume":"280","author":"Shin","year":"2005","journal-title":"J Biol Chem"},{"key":"2022102819180852300_dkac278-B27","doi-asserted-by":"crossref","first-page":"5092","DOI":"10.1128\/jb.178.17.5092-5099.1996","article-title":"Molecular basis of the magnesium deprivation response in Salmonella Typhimurium: identification of PhoP-regulated genes","volume":"178","author":"Soncini","year":"1996","journal-title":"J Bacteriol"},{"key":"2022102819180852300_dkac278-B28","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1365-2958.2012.08036.x","article-title":"The promoter architectural landscape of the Salmonella PhoP regulon","volume":"84","author":"Zwir","year":"2012","journal-title":"Mol Microbiol"},{"key":"2022102819180852300_dkac278-B29","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/(SICI)1521-1878(199801)20:1<96::AID-BIES13>3.0.CO;2-3","article-title":"The ins and outs of virulence gene expression: Mg2\u200a+\u200aas a regulatory signal","volume":"20","author":"Groisman","year":"1998","journal-title":"Bioessays"},{"key":"2022102819180852300_dkac278-B30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1365-2958.2005.04668.x","article-title":"The PhoP\/PhoQ system controls the intramacrophage type three secretion system of Salmonella enterica","volume":"57","author":"Bijlsma","year":"2005","journal-title":"Mol Microbiol"},{"key":"2022102819180852300_dkac278-B31","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1128\/IAI.01080-12","article-title":"Genome expression analysis of nonproliferating intracellular Salmonella enterica serovar Typhimurium unravels an acid pH-dependent PhoP-PhoQ response essential for dormancy","volume":"81","author":"N\u00fa\u00f1ez-Hern\u00e1ndez","year":"2013","journal-title":"Infect Immun"},{"key":"2022102819180852300_dkac278-B32","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.bbapap.2005.07.035","article-title":"Reversible phosphorylation of histidine residues in vertebrate proteins","volume":"1754","author":"Klumpp","year":"2005","journal-title":"Biochim Biophys Acta"},{"key":"2022102819180852300_dkac278-B33","doi-asserted-by":"crossref","first-page":"D509","DOI":"10.1093\/nar\/gkv1319","article-title":"StreptomeDB 2.0\u2014an extended resource of natural products produced by streptomycetes","volume":"44","author":"Klementz","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2022102819180852300_dkac278-B34","doi-asserted-by":"crossref","first-page":"e15179","DOI":"10.1371\/journal.pone.0015179","article-title":"A differential drug screen for compounds that select against antibiotic resistance","volume":"5","author":"Chait","year":"2010","journal-title":"PLoS One"},{"key":"2022102819180852300_dkac278-B35","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/pca.2482","article-title":"A thin-layer chromatography autographic method for the detection of inhibitors of the Salmonella PhoP-PhoQ regulatory system","volume":"25","author":"Salazar","year":"2014","journal-title":"Phytochem Anal"},{"key":"2022102819180852300_dkac278-B36","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.indcrop.2017.05.005","article-title":"Soybean hulls, an alternative source of bioactive compounds: combining pyrolysis with bioguided fractionation","volume":"105","author":"Giri","year":"2017","journal-title":"Ind Crops Prod"},{"key":"2022102819180852300_dkac278-B37","first-page":"313","article-title":"Methods for characterization of Streptomyces species","volume":"16","author":"Shirling","year":"1966","journal-title":"Int J Syst Evol Microbiol"},{"key":"2022102819180852300_dkac278-B38","volume-title":"Practical Streptomyces Genetics","author":"Kieser","year":"2000"},{"key":"2022102819180852300_dkac278-B39","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.chom.2013.11.010","article-title":"An infection-relevant transcriptomic compendium for Salmonella enterica serovar Typhimurium","volume":"14","author":"Kr\u00f6ger","year":"2013","journal-title":"Cell Host Microbe"},{"key":"2022102819180852300_dkac278-B40","doi-asserted-by":"crossref","first-page":"4742","DOI":"10.1128\/jb.171.9.4742-4751.1989","article-title":"Magnesium transport in Salmonella typhimurium: genetic characterization and cloning of three magnesium transport loci","volume":"171","author":"Hmiel","year":"1989","journal-title":"J Bacteriol"},{"key":"2022102819180852300_dkac278-B41","volume-title":"Advanced Bacterial Genetics","author":"Davis","year":"1980"},{"key":"2022102819180852300_dkac278-B42","doi-asserted-by":"crossref","first-page":"6640","DOI":"10.1073\/pnas.120163297","article-title":"One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products","volume":"97","author":"Datsenko","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022102819180852300_dkac278-B43","volume-title":"Experiments in molecular genetics","author":"Miller","year":"1972"},{"key":"2022102819180852300_dkac278-B44","first-page":"66","article-title":"Structure of azomycin (2-nitro-imidazole)","volume":"8","author":"Nakamura","year":"1955","journal-title":"J Antibiot"},{"key":"2022102819180852300_dkac278-B45","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.7164\/antibiotics.42.1513","article-title":"Isolation of azomycin from Pseudomonas fluorescens","volume":"42","author":"Shoji","year":"1989","journal-title":"J Antibiot (Tokyo)"},{"key":"2022102819180852300_dkac278-B46","doi-asserted-by":"crossref","first-page":"462","DOI":"10.7164\/antibiotics.43.462","article-title":"Studies on inhibitors of rat mast cell degranulation produced by microorganisms. I. Screening of microorganisms, and isolation and physico-chemical properties of eurocidins c, d and e","volume":"43","author":"Nakagomi","year":"1990","journal-title":"J Antibiot (Tokyo)"},{"key":"2022102819180852300_dkac278-B47","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3727\/095535491820873191","article-title":"Use of an aqueous soluble tetrazolium\/formazan assay for cell growth assays in culture","volume":"3","author":"Cory","year":"1991","journal-title":"Cancer Commun"},{"key":"2022102819180852300_dkac278-B48","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-1-61779-012-6_9","article-title":"Optimization of the tetrazolium dye (MTT) colorimetric assay for cellular growth and viability","volume":"716","author":"Sylvester","year":"2011","journal-title":"Methods Mol Biol"},{"key":"2022102819180852300_dkac278-B49","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/0076-6879(94)36030-8","article-title":"Measurement of invasion by gentamicin resistance","volume":"236","author":"Elsinghorst","year":"1994","journal-title":"Methods Enzymol"},{"key":"2022102819180852300_dkac278-B50","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1099\/mic.0.048926-0","article-title":"Contribution of the PhoP\/Q regulon to survival and replication of Salmonella enterica serovar Typhimurium in macrophages","volume":"157","author":"Thompson","year":"2011","journal-title":"Microbiology (Reading)"},{"key":"2022102819180852300_dkac278-B51","doi-asserted-by":"crossref","first-page":"4364","DOI":"10.1128\/jb.177.15.4364-4371.1995","article-title":"Transcriptional autoregulation of the Salmonella Typhimurium phoPQ operon","volume":"177","author":"Soncini","year":"1995","journal-title":"J Bacteriol"},{"key":"2022102819180852300_dkac278-B52","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/j.1365-2958.1990.tb00681.x","article-title":"Signal transduction and gene regulation through the phosphorylation of two regulatory components: the molecular basis for the osmotic regulation of the porin genes","volume":"4","author":"Mizuno","year":"1990","journal-title":"Mol Microbiol"},{"key":"2022102819180852300_dkac278-B53","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1128\/mr.53.4.450-490.1989","article-title":"Protein phosphorylation and regulation of adaptive responses in bacteria","volume":"53","author":"Stock","year":"1989","journal-title":"Microbiol Rev"},{"key":"2022102819180852300_dkac278-B54","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/BF00331499","article-title":"OmpR and EnvZ are pleiotropic regulatory proteins: positive regulation of the tripeptide permease (tppB) of Salmonella typhimurium","volume":"207","author":"Gibson","year":"1987","journal-title":"Mol Gen Genet"},{"key":"2022102819180852300_dkac278-B55","doi-asserted-by":"crossref","first-page":"11573","DOI":"10.1073\/pnas.1603192113","article-title":"Compartment and signal-specific codependence in the transcriptional control of Salmonella periplasmic copper homeostasis","volume":"113","author":"Pezza","year":"2016","journal-title":"Proc Natl Acad Sci"},{"key":"2022102819180852300_dkac278-B56","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1111\/j.1365-2958.2007.05590.x","article-title":"Bacterial sensing of and resistance to gold salts","volume":"63","author":"Checa","year":"2007","journal-title":"Mol Microbiol"},{"key":"2022102819180852300_dkac278-B57","first-page":"105","article-title":"Production of tertiomycin (a new antibiotic substance), azomycin and eurocidin by S. eurocidicus","volume":"8","author":"Osato","year":"1955","journal-title":"J Antibiot (Tokyo)"},{"key":"2022102819180852300_dkac278-B58","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1248\/cpb1953.3.379","article-title":"Structure of azomycin, a new antibiotic","volume":"3","author":"Nakamura","year":"1955","journal-title":"Pharm Bull"},{"key":"2022102819180852300_dkac278-B59","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ijantimicag.2008.02.022","article-title":"Bactericidal activity of 2-nitroimidazole against the active replicating stage of Mycobacterium bovis BCG and Mycobacterium tuberculosis with intracellular efficacy in THP-1 macrophages","volume":"32","author":"Khan","year":"2008","journal-title":"Int J Antimicrob Agents"},{"key":"2022102819180852300_dkac278-B60","doi-asserted-by":"crossref","first-page":"104821","DOI":"10.1016\/j.biocontrol.2021.104821","article-title":"Streptomyces eurocidicus promotes soybean growth and protects it from fungal infections","volume":"165","author":"Bercovich","year":"2022","journal-title":"Biol Control"},{"key":"2022102819180852300_dkac278-B61","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1128\/IAI.01336-13","article-title":"Repression of flagella is a common trait in field isolates of Salmonella enterica serovar Dublin and is associated with invasive human infections","volume":"82","author":"Yim","year":"2014","journal-title":"Infect Immun"},{"key":"2022102819180852300_dkac278-B62","doi-asserted-by":"crossref","first-page":"e00340-16","DOI":"10.1128\/genomeA.00340-16","article-title":"Whole-genome sequence of Salmonella enterica serovar Enteritidis phage type 4, isolated from a Brazilian poultry farm","volume":"4","author":"Milanez","year":"2016","journal-title":"Genome Announc"},{"key":"2022102819180852300_dkac278-B63","article-title":"Phenotypic and genotypic characterization of Salmonella Typhimurium isolates from humans and foods in Brazil","volume":"15","author":"Seribelli","year":"2020","journal-title":"PLoS One"},{"key":"2022102819180852300_dkac278-B64","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1146\/annurev-genet-051313-051025","article-title":"Bacterial Mg2+ homeostasis, transport, and virulence","volume":"47","author":"Groisman","year":"2013","journal-title":"Annu Rev Genet"},{"key":"2022102819180852300_dkac278-B65","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1128\/JB.06820-11","article-title":"The PhoP\/PhoQ system and its role in Serratia marcescens pathogenesis","volume":"194","author":"Barchiesi","year":"2012","journal-title":"J Bacteriol"},{"key":"2022102819180852300_dkac278-B66","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1074\/jbc.272.3.1440","article-title":"Characterization of the bacterial sensor protein PhoQ","volume":"272","author":"Garc\u00eda V\u00e9scovi","year":"1997","journal-title":"J Biol Chem"},{"key":"2022102819180852300_dkac278-B67","doi-asserted-by":"crossref","first-page":"22948","DOI":"10.1074\/jbc.M909335199","article-title":"The phosphatase activity is the target for Mg2\u200a+\u200aregulation of the sensor protein PhoQ in Salmonella","volume":"275","author":"Castelli","year":"2000","journal-title":"J Biol Chem"},{"key":"2022102819180852300_dkac278-B68","doi-asserted-by":"crossref","first-page":"679","DOI":"10.2165\/00003495-199754050-00003","article-title":"Metronidazole: a therapeutic review and update","volume":"54","author":"Freeman","year":"1997","journal-title":"Drugs"},{"key":"2022102819180852300_dkac278-B69","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0006-2952(86)90554-X","article-title":"Reduction of nitroimidazoles in vitro and DNA damage","volume":"35","author":"Edwards","year":"1986","journal-title":"Biochem Pharmacol"},{"key":"2022102819180852300_dkac278-B70","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1128\/AAC.43.7.1533","article-title":"Why metronidazole is active against both bacteria and parasites","volume":"43","author":"Samuelson","year":"1999","journal-title":"Antimicrob Agents Chemother"},{"key":"2022102819180852300_dkac278-B71","doi-asserted-by":"crossref","first-page":"e400","DOI":"10.1371\/journal.pbio.0020400","article-title":"Exploiting thiol modifications","volume":"2","author":"Kiley","year":"2004","journal-title":"PLoS Biol"},{"key":"2022102819180852300_dkac278-B72","doi-asserted-by":"crossref","first-page":"7502","DOI":"10.1073\/pnas.96.13.7502","article-title":"Virulent Salmonella typhimurium has two periplasmic Cu, Zn-superoxide dismutases","volume":"96","author":"Fang","year":"1999","journal-title":"Proc Natl Acad Sci"},{"key":"2022102819180852300_dkac278-B73","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1128\/JB.00144-09","article-title":"Redundant hydrogen peroxide scavengers contribute to Salmonella virulence and oxidative stress resistance","volume":"191","author":"H\u00e9brard","year":"2009","journal-title":"J Bacteriol"},{"key":"2022102819180852300_dkac278-B74","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1006\/jmbi.2000.3848","article-title":"Acetyl phosphate-dependent activation of a mutant PhoP response regulator that functions independently of its cognate sensor kinase","volume":"300","author":"Chamnongpol","year":"2000","journal-title":"J Mol Biol"},{"key":"2022102819180852300_dkac278-B75","doi-asserted-by":"crossref","first-page":"5054","DOI":"10.1073\/pnas.86.13.5054","article-title":"A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence","volume":"86","author":"Miller","year":"1989","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022102819180852300_dkac278-B76","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1126\/science.2646710","article-title":"A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells","volume":"243","author":"Fields","year":"1989","journal-title":"Science"},{"key":"2022102819180852300_dkac278-B77","first-page":"182","article-title":"A new antibiotic, azomycin","volume":"6","author":"Maeda","year":"1953","journal-title":"J Antibiot"},{"key":"2022102819180852300_dkac278-B78","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1039\/C0NP00024H","article-title":"Naturally-occurring nitro compounds","volume":"28","author":"Parry","year":"2010","journal-title":"Nat Prod Rep"},{"key":"2022102819180852300_dkac278-B79","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/B978-0-08-091283-7.00074-6","article-title":"7.14 - Covalent modification of DNA by natural products","volume":"7","author":"Gates","year":"1999","journal-title":"Comprehensive Natural Products Chemistry"},{"key":"2022102819180852300_dkac278-B80","doi-asserted-by":"crossref","first-page":"7636","DOI":"10.1021\/acs.jmedchem.7b00143","article-title":"Nitroimidazoles: molecular fireworks that combat a broad spectrum of infectious diseases","volume":"60","author":"Ang","year":"2017","journal-title":"J Med Chem"},{"key":"2022102819180852300_dkac278-B81","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/j.1747-0285.2012.01362.x","article-title":"Inhibition of bacterial virulence: drug-like molecules targeting the Salmonella enterica PhoP response regulator","volume":"79","author":"Tang","year":"2012","journal-title":"Chem Biol Drug Des"},{"key":"2022102819180852300_dkac278-B82","doi-asserted-by":"crossref","first-page":"9308","DOI":"10.1039\/C9RA00620F","article-title":"Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches","volume":"9","author":"Tsai","year":"2019","journal-title":"RSC Adv"},{"key":"2022102819180852300_dkac278-B83","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s12539-015-0273-x","article-title":"Computational analysis and in silico predictive modeling for inhibitors of PhoP regulon in S. Typhi on high-throughput screening bioassay dataset","volume":"8","author":"Kaur","year":"2015","journal-title":"Interdiscip Sci Comput Life Sci"},{"key":"2022102819180852300_dkac278-B84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0165-1218(78)90089-7","article-title":"Screening for the mutagenicity of nitro-group containing hypoxic cell radiosensitizers using Salmonella typhimurium strains TA 100 and TA 98","volume":"58","author":"Chin","year":"1978","journal-title":"Mutat Res Toxicol"},{"key":"2022102819180852300_dkac278-B85","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0165-1110(81)90006-3","article-title":"On the mutagenicity of nitroimidazoles","volume":"86","author":"Voogd","year":"1981","journal-title":"Mutat Res Genet Toxicol"},{"key":"2022102819180852300_dkac278-B86","first-page":"561","article-title":"Functionalized nitroimidazole scaffold construction and their pharmaceutical applications: a 1950-2021 comprehensive overview","volume":"15","author":"Gupta","year":"2022","journal-title":"Pharm"},{"key":"2022102819180852300_dkac278-B87","first-page":"149","article-title":"The mutagenic action of nitroimidazoles II. Effects of 2-nitroimidazoles","volume":"31","author":"Voogd","year":"1975","journal-title":"Mutat Res Mutagen Relat Subj"},{"key":"2022102819180852300_dkac278-B88","doi-asserted-by":"crossref","first-page":"855","DOI":"10.2174\/1386207319666161010163249","article-title":"A high-throughput assay for developing inhibitors of PhoP, a virulence factor of Mycobacterium tuberculosis","volume":"19","author":"Wang","year":"2016","journal-title":"Comb Chem High Throughput Screen"},{"key":"2022102819180852300_dkac278-B89","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1073\/pnas.83.14.5189","article-title":"Mutants of Salmonella Typhimurium that cannot survive within the macrophage are avirulent","volume":"83","author":"Fields","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022102819180852300_dkac278-B90","doi-asserted-by":"crossref","first-page":"6889","DOI":"10.1128\/JB.00804-06","article-title":"PhoP-induced genes within Salmonella pathogenicity island 1","volume":"188","author":"Aguirre","year":"2006","journal-title":"J Bacteriol"},{"key":"2022102819180852300_dkac278-B91","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000788","article-title":"Feedback inhibition in the PhoQ\/PhoP signaling system by a membrane peptide","volume":"5","author":"Lippa","year":"2009","journal-title":"PLoS Genet"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/11\/3050\/46680372\/dkac278.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/11\/3050\/46680372\/dkac278.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T19:21:21Z","timestamp":1666984881000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/77\/11\/3050\/6668240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,16]]},"references-count":91,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,8,16]]},"published-print":{"date-parts":[[2022,10,28]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkac278","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,11,2]]},"published":{"date-parts":[[2022,8,16]]}}}