title: Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli.
abstract: We recently reported that carbon monoxide (CO) has bactericidal activity. To understand its mode of action we analysed the gene expression changes occurring when Escherichia coli, grown aerobically and anaerobically, is treated with the CO-releasing molecule CORM-2 (tricarbonyldichlororuthenium(II) dimer). Microarray analysis shows that the E. coli CORM-2 response is multifaceted, with a high number of differentially regulated genes spread through several functional categories, namely genes involved in inorganic ion transport and metabolism, regulators, and genes implicated in post-translational modification, such as chaperones. CORM-2 has a higher impact in E. coli cells grown anaerobically, as judged by the repression of genes belonging to eight functional classes which are not seen in the response of aerobically CORM-2-treated cells. The biological relevance of the variations caused by CORM-2 was substantiated by studying the CORM-2 sensitivity of selected E. coli mutants. The results show that the deletion of redox-sensing regulators SoxS and OxyR increased the sensitivity to CORM-2 and suggest that while SoxS plays an important role in protection against CORM-2 under both growth conditions, OxyR seems to participate only in the aerobic CORM-2 response. Under anaerobic conditions, we found that the heat-shock proteins IbpA and IbpB contribute to CORM-2 defence since the deletion of these genes increases the sensitivity of the strain. The induction of several met genes and the hypersensitivity to CORM-2 of the DeltametR, DeltametI and DeltametN mutant strains suggest that CO has effects on the methionine metabolism of E. coli. CORM-2 also affects the transcription of several E. coli biofilm-related genes and increases biofilm formation in E. coli. In particular, the absence of tqsA or bhsA increases the resistance of E. coli to CORM-2, and deletion of tsqA leads to a strain that has lost its capacity to form biofilm upon treatment with CORM-2. In spite of the relatively stable nature of the CO molecule, our results show that CO is able to trigger a significant alteration in the transcriptome of E. coli which necessarily has effects in several key metabolic pathways.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Avenida da República (EAN), 2780-157 Oeiras, Portugal.
authors.forename: Lígia S
authors.initials: LS
authors.lastname: Nobre
authors.affiliation: Department of Bioinformatics, Centro de Investigación Príncipe Felipe (CIPF), Valencia, E-46013, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Al-Shahrour
authors.affiliation: Functional Genomics Node (National Institute for Bioinformatics, INB), Centro de Investigación Príncipe Felipe (CIPF), Valencia, E-46013, Spain.|Center for Biomedical Research on Rare Diseases (CIBERER), Centro de Investigación Príncipe Felipe (CIPF), Valencia, E-46013, Spain.|Department of Bioinformatics, Centro de Investigación Príncipe Felipe (CIPF), Valencia, E-46013, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Avenida da República (EAN), 2780-157 Oeiras, Portugal.
authors.forename: Lígia M
authors.initials: LM
authors.lastname: Saraiva
mesh_terms: D018441:Biofilms; D002248:Carbon Monoxide / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005809:Genes, Regulator; D005816:Genetic Complementation Test; D008715:Methionine / Q000378:metabolism; D050296:Microbial Viability; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D009942:Organometallic Compounds / Q000494:pharmacology*; D010641:Phenotype; D012329:RNA, Bacterial / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; D009942:Organometallic Compounds; D012329:RNA, Bacterial; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D008715:Methionine