{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T08:51:18Z","timestamp":1774083078718,"version":"3.50.1"},"reference-count":77,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD16\/0016\/0011"],"award-info":[{"award-number":["RD16\/0016\/0011"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006541","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["S2017\/BMD-3691"],"award-info":[{"award-number":["S2017\/BMD-3691"]}],"id":[{"id":"10.13039\/501100006541","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MCIN\/AEI \/10.13039\/501100011033","award":["PID2020-113521RB-I00"],"award-info":[{"award-number":["PID2020-113521RB-I00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Stenotrophomonas maltophilia is an opportunistic pathogen with an environmental origin, which presents a characteristically low susceptibility to antibiotics and is capable of acquiring increased levels of resistance to antimicrobials. Among these, fosfomycin resistance seems particularly intriguing; resistance to this antibiotic is generally due to the activity of fosfomycin-inactivating enzymes, or to defects in the expression or the activity of fosfomycin transporters. In contrast, we previously described that the cause of fosfomycin resistance in S. maltophilia was the inactivation of enzymes belonging to its central carbon metabolism. To go one step further, here we studied the effects of fosfomycin on the transcriptome of S. maltophilia compared to those of phosphoenolpyruvate\u2014its structural homolog\u2014and glyceraldehyde-3-phosphate\u2014an intermediate metabolite of the mutated route in fosfomycin-resistant mutants. Our results show that transcriptomic changes present a large degree of overlap, including the activation of the cell-wall-stress stimulon. These results indicate that fosfomycin activity and resistance are interlinked with bacterial metabolism. Furthermore, we found that the studied compounds inhibit the expression of the smeYZ efflux pump, which confers intrinsic resistance to aminoglycosides. This is the first description of efflux pump inhibitors that can be used as antibiotic adjuvants to counteract antibiotic resistance in S. maltophilia.<\/jats:p>","DOI":"10.3390\/ijms23010159","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T21:40:21Z","timestamp":1640295621000},"page":"159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Antibiotic Fosfomycin Mimics the Effects of the Intermediate Metabolites Phosphoenolpyruvate and Glyceraldehyde-3-Phosphate on the Stenotrophomonas maltophilia Transcriptome"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0136-3965","authenticated-orcid":false,"given":"Teresa","family":"Gil-Gil","sequence":"first","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, CSIC, Darwin 3, 28049 Madrid, Spain"},{"name":"Programa de Doctorado en Biociencias Moleculares, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luz Edith","family":"Ochoa-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, CSIC, Darwin 3, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-7607","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, CSIC, Darwin 3, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/S1359-6446(05)03566-X","article-title":"Using microarray gene signatures to elucidate mechanisms of antibiotic action and resistance","volume":"10","author":"Brazas","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fajardo, A., Martinez-Martin, N., Mercadillo, M., Galan, J.C., Ghysels, B., Matthijs, S., Cornelis, P., Wiehlmann, L., Tummler, B., and Baquero, F. (2008). The neglected intrinsic resistome of bacterial pathogens. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001619"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"19484","DOI":"10.1073\/pnas.0608949103","article-title":"Antibiotics as intermicrobial signaling agents instead of weapons","volume":"103","author":"Linares","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.envpol.2004.10.001","article-title":"Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences","volume":"138","author":"Calabrese","year":"2005","journal-title":"Environ. Pollut."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.mib.2006.08.006","article-title":"The world of subinhibitory antibiotic concentrations","volume":"9","author":"Davies","year":"2006","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1101\/gr.157701","article-title":"Gene expression changes triggered by exposure of Haemophilus influenzae to novobiocin or ciprofloxacin: Combined transcription and translation analysis","volume":"11","author":"Gmuender","year":"2001","journal-title":"Genome Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1126\/science.1159483","article-title":"Antibiotics and antibiotic resistance genes in natural environments","volume":"321","author":"Martinez","year":"2008","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/CMR.00019-11","article-title":"Stenotrophomonas maltophilia: An emerging global opportunistic pathogen","volume":"25","author":"Brooke","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1038\/s41467-020-15123-0","article-title":"The phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist Stenotrophomonas maltophilia","volume":"11","author":"Groschel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ijantimicag.2004.10.002","article-title":"Antimicrobial susceptibility of uncommonly isolated non-enteric Gram-negative bacilli","volume":"25","author":"Sader","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"655","DOI":"10.2217\/fmb.09.45","article-title":"Stenotrophomonas maltophilia drug resistance","volume":"4","author":"Sanchez","year":"2009","journal-title":"Future Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1126\/science.166.3901.122","article-title":"Phosphonomycin, a new antibiotic produced by strains of streptomyces","volume":"166","author":"Hendlin","year":"1969","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/j.1749-6632.1974.tb43277.x","article-title":"The mechanism of action of fosfomycin (phosphonomycin)","volume":"235","author":"Kahan","year":"1974","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/S0969-2126(96)00153-0","article-title":"Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin","volume":"4","author":"Skarzynski","year":"1996","journal-title":"Structure"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1128\/CMR.00068-15","article-title":"Fosfomycin","volume":"29","author":"Falagas","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1128\/JB.185.4.1218-1228.2003","article-title":"In vitro and in vivo functional activity of Chlamydia MurA, a UDP-N-acetylglucosamine enolpyruvyl transferase involved in peptidoglycan synthesis and fosfomycin resistance","volume":"185","author":"McCoy","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1099\/00221287-145-11-3177","article-title":"Alteration of a single amino acid residue reverses fosfomycin resistance of recombinant MurA from Mycobacterium tuberculosis","volume":"145","author":"Kempsell","year":"1999","journal-title":"Microbiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1021\/bi1017842","article-title":"Lyme disease enolpyruvyl-UDP-GlcNAc synthase: Fosfomycin-resistant MurA from Borrelia burgdorferi, a fosfomycin-sensitive mutant, and the catalytic role of the active site Asp","volume":"50","author":"Jiang","year":"2011","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4923","DOI":"10.1021\/bi952937w","article-title":"Characterization of a Cys115 to Asp substitution in the Escherichia coli cell wall biosynthetic enzyme UDP-GlcNAc enolpyruvyl transferase (MurA) that confers resistance to inactivation by the antibiotic fosfomycin","volume":"35","author":"Kim","year":"1996","journal-title":"Biochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1128\/jb.110.3.935-944.1972","article-title":"Isolation and characterization of a phosphonomycin-resistant mutant of Escherichia coli K-12","volume":"110","author":"Venkateswaran","year":"1972","journal-title":"J. Bacteriol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1128\/AAC.06122-11","article-title":"Genomewide overexpression screen for fosfomycin resistance in Escherichia coli: MurA confers clinical resistance at low fitness cost","volume":"56","author":"Couce","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00203-009-0468-9","article-title":"Identification of a novel UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) from Vibrio fischeri that confers high fosfomycin resistance in Escherichia coli","volume":"191","author":"Kumar","year":"2009","journal-title":"Arch. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nchembio.1289","article-title":"A cell wall recycling shortcut that bypasses peptidoglycan de novo biosynthesis","volume":"9","author":"Gisin","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1128\/jb.113.2.895-900.1973","article-title":"Isolation and characterization of mutations affecting the transport of hexose phosphates in Escherichia coli","volume":"113","author":"Kadner","year":"1973","journal-title":"J. Bacteriol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"906","DOI":"10.7164\/antibiotics.28.906","article-title":"Charactertization of spontaneous fosfomycin (phosphonomycin)-resistant cells of Escherichia coli B in vitro","volume":"28","author":"Tsuruoka","year":"1975","journal-title":"J. Antibiot."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sass, P., Jansen, A., Szekat, C., Sass, V., Sahl, H.G., and Bierbaum, G. (2008). The lantibiotic mersacidin is a strong inducer of the cell wall stress response of Staphylococcus aureus. BMC Microbiol., 8.","DOI":"10.1186\/1471-2180-8-186"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0076-6879(05)01023-2","article-title":"Fosfomycin resistance proteins: A nexus of glutathione transferases and epoxide hydrolases in a metalloenzyme superfamily","volume":"401","author":"Rigsby","year":"2005","journal-title":"Methods Enzymol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1574-6968.1991.tb04580.x","article-title":"Characterization of staphylococcal plasmids hybridizing with the fosfomycin resistance gene fosB","volume":"68","author":"Etienne","year":"1991","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1021\/bi963172a","article-title":"Fosfomycin resistance protein (FosA) is a manganese metalloglutathione transferase related to glyoxalase I and the extradiol dioxygenases","volume":"36","author":"Bernat","year":"1997","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8110","DOI":"10.1021\/bi700625p","article-title":"Structure and mechanism of the genomically encoded fosfomycin resistance protein, FosX, from Listeria monocytogenes","volume":"46","author":"Fillgrove","year":"2007","journal-title":"Biochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e00282-20","DOI":"10.1128\/mSystems.00282-20","article-title":"The Inactivation of Enzymes Belonging to the Central Carbon Metabolism Is a Novel Mechanism of Developing Antibiotic Resistance","volume":"5","author":"Corona","year":"2020","journal-title":"mSystems"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/0923-2508(96)83998-2","article-title":"Evolution of carbohydrate metabolic pathways","volume":"147","author":"Romano","year":"1996","journal-title":"Res. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1128\/AAC.11.1.147","article-title":"L-Glyceraldehude 3-phosphate, a bactericidal agent","volume":"11","author":"Tang","year":"1977","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Petek, M., Baebler, S., Kuzman, D., Rotter, A., Podlesek, Z., Gruden, K., Ravnikar, M., and Urleb, U. (2010). Revealing fosfomycin primary effect on Staphylococcus aureus transcriptome: Modulation of cell envelope biosynthesis and phosphoenolpyruvate induced starvation. BMC Microbiol., 10.","DOI":"10.1186\/1471-2180-10-159"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.abb.2011.08.003","article-title":"Inhibition of mitochondrial respiration by phosphoenolpyruvate","volume":"514","author":"Baily","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1099\/mic.0.26426-0","article-title":"Genome-wide transcriptional profiling of the response of Staphylococcus aureus to cell-wall-active antibiotics reveals a cell-wall-stress stimulon","volume":"149","author":"Utaida","year":"2003","journal-title":"Microbiology"},{"key":"ref_37","first-page":"79","article-title":"Cell wall-active antibiotic induced proteins of Staphylococcus aureus identified using a proteomic approach","volume":"199","author":"Singh","year":"2001","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yamaguchi, Y., Tomoyasu, T., Takaya, A., Morioka, M., and Yamamoto, T. (2003). Effects of disruption of heat shock genes on susceptibility of Escherichia coli to fluoroquinolones. BMC Microbiol., 3.","DOI":"10.1186\/1471-2180-3-16"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bayer-Santos, E., Cenens, W., Matsuyama, B.Y., Oka, G.U., Di Sessa, G., Mininel, I.D.V., Alves, T.L., and Farah, C.S. (2019). The opportunistic pathogen Stenotrophomonas maltophilia utilizes a type IV secretion system for interbacterial killing. PLoS Pathog., 15.","DOI":"10.1101\/557322"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00457-19","DOI":"10.1128\/IAI.00457-19","article-title":"Stenotrophomonas maltophilia Encodes a VirB\/VirD4 Type IV Secretion System That Modulates Apoptosis in Human Cells and Promotes Competition against Heterologous Bacteria, Including Pseudomonas aeruginosa","volume":"87","author":"Nas","year":"2019","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1128\/JB.187.7.2315-2325.2005","article-title":"Identification of new protein-protein interactions involving the products of the chromosome- and plasmid-encoded type IV secretion loci of the phytopathogen Xanthomonas axonopodis pv. citri","volume":"187","author":"Alegria","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1128\/MMBR.00024-06","article-title":"How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria","volume":"70","author":"Deutscher","year":"2006","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1128\/jb.128.3.785-793.1976","article-title":"Fosfomycin resistance: Selection method for internal and extended deletions of the phosphoenolpyruvate: Sugar phosphotransferase genes of Salmonella typhimurium","volume":"128","author":"Cordaro","year":"1976","journal-title":"J. Bacteriol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26185","DOI":"10.1074\/jbc.274.37.26185","article-title":"Enzyme I(Ntr) from Escherichia coli. A novel enzyme of the phosphoenolpyruvate-dependent phosphotransferase system exhibiting strict specificity for its phosphoryl acceptor, NPr","volume":"274","author":"Rabus","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e00154-16","DOI":"10.1128\/mSystems.00154-16","article-title":"A Metabolic Widget Adjusts the Phosphoenolpyruvate-Dependent Fructose Influx in Pseudomonas putida","volume":"1","author":"Nikel","year":"2016","journal-title":"mSystems"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/bib\/bbx085","article-title":"The BioCyc collection of microbial genomes and metabolic pathways","volume":"20","author":"Karp","year":"2019","journal-title":"Brief. Bioinform."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/j.bbrc.2017.11.188","article-title":"Probing transport of fosfomycin through substrate specific OprO and OprP from Pseudomonas aeruginosa","volume":"495","author":"Citak","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1146\/annurev.micro.56.012302.160310","article-title":"Function of pseudomonas porins in uptake and efflux","volume":"56","author":"Hancock","year":"2002","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1128\/AAC.48.8.3057-3063.2004","article-title":"Regulation of the expression of cell wall stress stimulon member gene msrA1 in methicillin-susceptible or -resistant Staphylococcus aureus","volume":"48","author":"Pechous","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/ars.2007.1672","article-title":"NAD+\/NADH and NADP+\/NADPH in cellular functions and cell death: Regulation and biological consequences","volume":"10","author":"Ying","year":"2008","journal-title":"Antioxid Redox Signal."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1046\/j.1365-2958.2001.02383.x","article-title":"Genetic dissection of the roles of chaperones and proteases in protein folding and degradation in the Escherichia coli cytosol","volume":"40","author":"Tomoyasu","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6934","DOI":"10.1093\/emboj\/18.24.6934","article-title":"Identification of thermolabile Escherichia coli proteins: Prevention and reversion of aggregation by DnaK and ClpB","volume":"18","author":"Mogk","year":"1999","journal-title":"EMBO J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1046\/j.1365-2958.2000.01951.x","article-title":"ClpB and HtpG facilitate de novo protein folding in stressed Escherichia coli cells","volume":"36","author":"Thomas","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15024","DOI":"10.1073\/pnas.93.26.15024","article-title":"Chaperone activity and structure of monomeric polypeptide binding domains of GroEL","volume":"93","author":"Zahn","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1365-2958.2009.06648.x","article-title":"The nature of Staphylococcus aureus MurA and MurZ and approaches for detection of peptidoglycan biosynthesis inhibitors","volume":"72","author":"Blake","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref_56","first-page":"2757","article-title":"Nucleotide sequence of fruA, the gene specifying enzyme IIfru of the phosphoenolpyruvate-dependent sugar phosphotransferase system in Escherichia coli K12","volume":"134","author":"Prior","year":"1988","journal-title":"J. Gen. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.bbagen.2009.07.017","article-title":"The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine","volume":"1800","author":"Hanover","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19302","DOI":"10.1073\/pnas.0609508103","article-title":"Conservation of the metabolomic response to starvation across two divergent microbes","volume":"103","author":"Brauer","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.1128\/AAC.00372-15","article-title":"The SmeYZ Efflux Pump of Stenotrophomonas maltophilia Contributes to Drug Resistance, Virulence-Related Characteristics, and Virulence in Mice","volume":"59","author":"Lin","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Liu, M.C., Tsai, Y.L., Huang, Y.W., Chen, H.Y., Hsueh, P.R., Lai, S.Y., Chen, L.C., Chou, Y.H., Lin, W.Y., and Liaw, S.J. (2016). Stenotrophomonas maltophilia PhoP, a Two-Component Response Regulator, Involved in Antimicrobial Susceptibilities. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153753"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e01263-18","DOI":"10.1128\/AAC.01263-18","article-title":"Biolog Phenotype Microarray Is a Tool for the Identification of Multidrug Resistance Efflux Pump Inducers","volume":"62","author":"Blanco","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/jac\/dkg148","article-title":"Role of the acetyltransferase AAC(6\u2032)-Iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia","volume":"51","author":"Li","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1128\/CMR.15.4.647-679.2002","article-title":"Interactions among strategies associated with bacterial infection: Pathogenicity, epidemicity, and antibiotic resistance","volume":"15","author":"Martinez","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e01950-17","DOI":"10.1128\/mBio.01950-17","article-title":"Interventions on Metabolism: Making Antibiotic-Susceptible Bacteria","volume":"8","author":"Baquero","year":"2017","journal-title":"mBio"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1128\/AAC.41.5.1140","article-title":"Multiple antibiotic resistance in Stenotrophomonas maltophilia","volume":"41","author":"Alonso","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1128\/AAC.45.6.1879-1881.2001","article-title":"Expression of multidrug efflux pump SmeDEF by clinical isolates of Stenotrophomonas maltophilia","volume":"45","author":"Alonso","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1042\/bj2380275","article-title":"Isolation and properties of the glycolytic enzymes from Zymomonas mobilis. The five enzymes from glyceraldehyde-3-phosphate dehydrogenase through to pyruvate kinase","volume":"238","author":"Pawluk","year":"1986","journal-title":"Biochem. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/BF02236391","article-title":"Classification of the bovine farcy organism","volume":"9","author":"Tag","year":"1977","journal-title":"Trop. Anim. Health Prod."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nmeth.3252","article-title":"Orchestrating high-throughput genomic analysis with Bioconductor","volume":"12","author":"Huber","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkz114","article-title":"The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): High-performance genomics data visualization and exploration","volume":"14","author":"Thorvaldsdottir","year":"2013","journal-title":"Brief. Bioinform."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_75","unstructured":"Oliveros, J.C. (2021, November 15). Venny. An Interactive Tool for Comparing Lists with Venn\u2019s Diagrams. Available online: https:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/159\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:52:29Z","timestamp":1760169149000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010159"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010159","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,23]]}}}