{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:54:04Z","timestamp":1790801644530,"version":"4.1.0"},"reference-count":91,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI113330"],"award-info":[{"award-number":["AI113330"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI094268"],"award-info":[{"award-number":["AI094268"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI113330"],"award-info":[{"award-number":["AI113330"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI094268"],"award-info":[{"award-number":["AI094268"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The bacterial heat-shock response is regulated by the alternative sigma factor, \u03c332 (RpoH), which responds to misfolded protein stress and directs the RNA polymerase to the promoters for genes required for protein refolding or degradation. In P. aeruginosa, RpoH is essential for viability under laboratory growth conditions. Here, we used a transcriptomics approach to identify the genes of the RpoH regulon, including RpoH-regulated genes that are essential for P. aeruginosa. We placed the rpoH gene under control of the arabinose-inducible PBAD promoter, then deleted the chromosomal rpoH allele. This allowed transcriptomic analysis of the RpoH (\u03c332) regulon following a short up-shift in the cellular concentration of RpoH by arabinose addition, in the absence of a sudden change in temperature. The P. aeruginosa \u2206rpoH (PBAD-rpoH) strain grew in the absence of arabinose, indicating that some rpoH expression occurred without arabinose induction. When arabinose was added, the rpoH mRNA abundance of P. aeruginosa \u2206rpoH (PBAD-rpoH) measured by RT-qPCR increased five-fold within 15 min of arabinose addition. Transcriptome results showed that P. aeruginosa genes required for protein repair or degradation are induced by increased RpoH levels, and that many genes essential for P. aeruginosa growth are induced by RpoH. Other stress response genes induced by RpoH are involved in damaged nucleic acid repair and in amino acid metabolism. Annotation of the hypothetical proteins under RpoH control included proteins that may play a role in antibiotic resistances and in non-ribosomal peptide synthesis. Phenotypic analysis of P. aeruginosa \u2206rpoH (PBAD-rpoH) showed that it is impaired in its ability to survive during starvation compared to the wild-type strain. P. aeruginosa \u2206rpoH (PBAD-rpoH) also had increased sensitivity to aminoglycoside antibiotics, but not to other classes of antibiotics, whether cultured planktonically or in biofilms. The enhanced aminoglycoside sensitivity of the mutant strain may be due to indirect effects, such as the build-up of toxic misfolded proteins, or to the direct effect of genes, such as aminoglycoside acetyl transferases, that are regulated by RpoH. Overall, the results demonstrate that RpoH regulates genes that are essential for viability of P. aeruginosa, that it protects P. aeruginosa from damage from aminoglycoside antibiotics, and that it is required for survival during nutrient-limiting conditions.<\/jats:p>","DOI":"10.3390\/ijms24021513","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T01:30:26Z","timestamp":1673573426000},"page":"1513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The Pseudomonas aeruginosa RpoH (\u03c332) Regulon and Its Role in Essential Cellular Functions, Starvation Survival, and Antibiotic Tolerance"],"prefix":"10.3390","volume":"24","author":[{"given":"Kerry S.","family":"Williamson","sequence":"first","affiliation":[{"name":"Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA"},{"name":"Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4315-1514","authenticated-orcid":false,"given":"Mensur","family":"Dlaki\u0107","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA"},{"name":"Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4587-6546","authenticated-orcid":false,"given":"Michael J.","family":"Franklin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA"},{"name":"Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0168-1605(00)00206-3","article-title":"The heat shock response of Escherichia coli","volume":"55","author":"Arsene","year":"2000","journal-title":"Int. J. Food Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0092-8674(84)90493-8","article-title":"The htpR gene product of E. coli is a sigma factor for heat-shock promoters","volume":"38","author":"Grossman","year":"1984","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1101\/gad.1.5.419","article-title":"Regulation of the promoters and transcripts of rpoH, the Escherichia coli heat shock regulatory gene","volume":"1","author":"Erickson","year":"1987","journal-title":"Genes Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1128\/MMBR.00007-08","article-title":"Convergence of molecular, modeling, and systems approaches for an understanding of the Escherichia coli heat shock response","volume":"72","author":"Guisbert","year":"2008","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1073\/pnas.82.9.2679","article-title":"Consensus sequence for Escherichia coli heat shock gene promoters","volume":"82","author":"Cowing","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1101\/gad.1428206","article-title":"Regulon and promoter analysis of the E. coli heat-shock factor, sigma32, reveals a multifaceted cellular response to heat stress","volume":"20","author":"Nonaka","year":"2006","journal-title":"Genes Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1128\/JB.01297-06","article-title":"Global gene expression and phenotypic analysis of a Vibrio cholerae rpoH deletion mutant","volume":"189","author":"Slamti","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7796","DOI":"10.1128\/JB.186.22.7796-7803.2004","article-title":"Global transcriptome analysis of the heat shock response of Shewanella oneidensis","volume":"186","author":"Gao","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1128\/JB.01807-05","article-title":"Comparison of the RpoH-dependent regulon and general stress response in Neisseria gonorrhoeae","volume":"188","author":"Gunesekere","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4983","DOI":"10.1128\/JB.00449-12","article-title":"Dual RpoH sigma factors and transcriptional plasticity in a symbiotic bacterium","volume":"194","author":"Barnett","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrmicro2415","article-title":"The biofilm matrix","volume":"8","author":"Flemming","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1128\/CMR.15.2.194-222.2002","article-title":"Lung infections associated with cystic fibrosis","volume":"15","author":"Lyczak","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00138-18","DOI":"10.1128\/CMR.00138-18","article-title":"Cystic Fibrosis and Pseudomonas aeruginosa: The Host-Microbe Interface","volume":"32","author":"Malhotra","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrmicro821","article-title":"Bacterial biofilms: From the natural environment to infectious diseases","volume":"2","author":"Costerton","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1146\/annurev.micro.56.012302.160705","article-title":"Biofilms as complex differentiated communities","volume":"56","author":"Stoodley","year":"2002","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.1128\/AAC.00433-15","article-title":"Contribution of stress responses to antibiotic tolerance in Pseudomonas aeruginosa biofilms","volume":"59","author":"Stewart","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00307-19","DOI":"10.1128\/JB.00307-19","article-title":"Conceptual model of biofilm antibiotic tolerance that integrates phenomena of diffusion, metabolism, gene expression, and physiology","volume":"201","author":"Stewart","year":"2019","journal-title":"J. Bacteriol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e0002122","DOI":"10.1128\/aac.00021-22","article-title":"Search for a shared genetic or biochemical basis for biofilm tolerance to antibiotics across bacterial species","volume":"66","author":"Stewart","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41579-022-00692-2","article-title":"Gradients and consequences of heterogeneity in biofilms","volume":"20","author":"Jo","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nrmicro1838","article-title":"Physiological heterogeneity in biofilms","volume":"6","author":"Stewart","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1128\/JB.00022-12","article-title":"Heterogeneity in Pseudomonas aeruginosa biofilms includes expression of ribosome hibernation factors in the antibiotic-tolerant subpopulation and hypoxia-induced stress response in the metabolically active population","volume":"194","author":"Williamson","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1073\/pnas.0708931105","article-title":"Asymmetric segregation of protein aggregates is associated with cellular aging and rejuvenation","volume":"105","author":"Lindner","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jmb.2008.12.009","article-title":"Distinct activities of Escherichia coli small heat shock proteins IbpA and IbpB promote efficient protein disaggregation","volume":"386","author":"Ratajczak","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/wrr.12401","article-title":"Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds","volume":"24","author":"James","year":"2016","journal-title":"Wound Repair Regen."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2223","DOI":"10.7717\/peerj.2223","article-title":"Transcriptome analysis of Pseudomonas aeruginosa PAO1 grown at both body and elevated temperatures","volume":"4","author":"Chan","year":"2016","journal-title":"PeerJ"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Schulz, S., Eckweiler, D., Bielecka, A., Nicolai, T., Franke, R., Dotsch, A., Hornischer, K., Bruchmann, S., Duvel, J., and Haussler, S. (2015). Elucidation of sigma factor-associated networks in Pseudomonas aeruginosa reveals a modular architecture with limited and function-specific crosstalk. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004744"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1128\/AAC.00935-10","article-title":"Involvement of an ATP-dependent protease, PA0779\/AsrA, in inducing heat shock in response to tobramycin in Pseudomonas aeruginosa","volume":"55","author":"Kindrachuk","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17758","DOI":"10.1074\/jbc.M500393200","article-title":"The global transcriptional response of Escherichia coli to induced sigma 32 protein involves sigma 32 regulon activation followed by inactivation and degradation of sigma 32 in vivo","volume":"280","author":"Zhao","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1073\/pnas.1419677112","article-title":"Essential genome of Pseudomonas aeruginosa in cystic fibrosis sputum","volume":"112","author":"Turner","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10072","DOI":"10.1073\/pnas.1900570116","article-title":"Defining the core essential genome of Pseudomonas aeruginosa","volume":"116","author":"Poulsen","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0378-1119(98)00601-5","article-title":"Broad-host-range expression vectors that carry the L-arabinose-inducible Escherichia coli araBAD promoter and the araC regulator","volume":"227","author":"Newman","year":"1999","journal-title":"Gene"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.1128\/AEM.02041-16","article-title":"The Escherichia coli rhaSR-PrhaBAD inducible promoter system allows tightly controlled gene expression over a wide range in Pseudomonas aeruginosa","volume":"82","author":"Meisner","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: Massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e00142-11","DOI":"10.1128\/mBio.00142-11","article-title":"Lipopolysaccharide (LPS) inner-core phosphates are required for complete LPS synthesis and transport to the outer membrane in Pseudomonas aeruginosa PAO1","volume":"2","author":"Delucia","year":"2011","journal-title":"mBio"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41598-019-56913-x","article-title":"Iron acquisition in Pseudomonas aeruginosa by the siderophore pyoverdine: An intricate interacting network including periplasmic and membrane proteins","volume":"10","author":"Bonneau","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1128\/AAC.00222-08","article-title":"Complex ciprofloxacin resistome revealed by screening a Pseudomonas aeruginosa mutant library for altered susceptibility","volume":"52","author":"Breidenstein","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e00315-10","DOI":"10.1128\/mBio.00315-10","article-title":"Genome-scale identification of resistance functions in Pseudomonas aeruginosa using Tn-seq","volume":"2","author":"Gallagher","year":"2011","journal-title":"mBio"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1111\/j.1365-2958.2004.04448.x","article-title":"The contribution of MvfR to Pseudomonas aeruginosa pathogenesis and quorum sensing circuitry regulation: Multiple quorum sensing-regulated genes are modulated without affecting lasRI, rhlRI or the production of N-acyl-L-homoserine lactones","volume":"55","author":"Deziel","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1046\/j.1365-2958.2002.03084.x","article-title":"GeneChip expression analysis of the iron starvation response in Pseudomonas aeruginosa: Identification of novel pyoverdine biosynthesis genes","volume":"45","author":"Ochsner","year":"2002","journal-title":"Mol. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1007\/s00203-003-0602-z","article-title":"Transcriptome analysis of the Pseudomonas aeruginosa response to iron","volume":"180","author":"Palma","year":"2003","journal-title":"Arch. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1046\/j.1365-2958.2003.03886.x","article-title":"The Pseudomonas aeruginosa RpoS regulon and its relationship to quorum sensing","volume":"51","author":"Schuster","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1365-2958.2007.05772.x","article-title":"Responses of Pseudomonas aeruginosa to low oxygen indicate that growth in the cystic fibrosis lung is by aerobic respiration","volume":"65","author":"Harwood","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1128\/JB.188.9.3365-3370.2006","article-title":"A distinct QscR regulon in the Pseudomonas aeruginosa quorum-sensing circuit","volume":"188","author":"Lequette","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1128\/AAC.50.5.1680-1688.2006","article-title":"Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: A global approach","volume":"50","author":"Nalca","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7242","DOI":"10.1128\/JB.00837-06","article-title":"Survival and growth in the presence of elevated copper: Transcriptional profiling of copper-stressed Pseudomonas aeruginosa","volume":"188","author":"Teitzel","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Chang, W., Small, D.A., Toghrol, F., and Bentley, W.E. (2005). Microarray analysis of Pseudomonas aeruginosa reveals induction of pyocin genes in response to hydrogen peroxide. BMC Genom., 6.","DOI":"10.1186\/1471-2164-6-115"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1002\/pmic.201000807","article-title":"Proteomics of the oxidative stress response induced by hydrogen peroxide and paraquat reveals a novel AhpC-like protein in Pseudomonas aeruginosa","volume":"11","author":"Hare","year":"2011","journal-title":"Proteomics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1128\/JB.186.1.248-252.2004","article-title":"Transcriptome analysis of the response of Pseudomonas aeruginosa to hydrogen peroxide","volume":"186","author":"Palma","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1128\/JB.187.8.2565-2572.2005","article-title":"Genome-wide transcriptional profiling of the steady-state response of Pseudomonas aeruginosa to hydrogen peroxide","volume":"187","author":"Salunkhe","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Folsom, J.P., Richards, L., Pitts, B., Roe, F., Ehrlich, G.D., Parker, A., Mazurie, A., and Stewart, P.S. (2010). Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome analysis. BMC Microbiol., 10.","DOI":"10.1186\/1471-2180-10-294"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1017\/S1479050505001699","article-title":"Transcriptome analysis of Pseudomonas aeruginosa biofilm development: Anaerobic respiration and iron limitation","volume":"2","author":"Hentzer","year":"2005","journal-title":"Biofilms"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1099\/mic.0.025551-0","article-title":"Biofilms and type III secretion are not mutually exclusive in Pseudomonas aeruginosa","volume":"155","author":"Mikkelsen","year":"2009","journal-title":"Microbiology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1128\/JB.01687-06","article-title":"Interrelationships between colonies, biofilms, and planktonic cells of Pseudomonas aeruginosa","volume":"189","author":"Mikkelsen","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.1099\/mic.0.2007\/010371-0","article-title":"Strain-specific proteome responses of Pseudomonas aeruginosa to biofilm-associated growth and to calcium","volume":"153","author":"Patrauchan","year":"2007","journal-title":"Microbiology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1128\/jb.184.4.1140-1154.2002","article-title":"Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm","volume":"184","author":"Sauer","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Waite, R.D., Paccanaro, A., Papakonstantinopoulou, A., Hurst, J.M., Saqi, M., Littler, E., and Curtis, M.A. (2006). Clustering of Pseudomonas aeruginosa transcriptomes from planktonic cultures, developing and mature biofilms reveals distinct expression profiles. BMC Genom., 7.","DOI":"10.1186\/1471-2164-7-162"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35101627","article-title":"Gene expression in Pseudomonas aeruginosa biofilms","volume":"413","author":"Whiteley","year":"2001","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Choi, K.-H., and Schweizer, H. (2005). An improved method for rapid generation of unmarked Pseudomonas aeruginosa deletion mutants. BMC Microbiol., 5.","DOI":"10.1186\/1471-2180-5-30"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3204","DOI":"10.1073\/pnas.1700695114","article-title":"Resuscitation of Pseudomonas aeruginosa from dormancy requires hibernation promoting factor (PA4463) for ribosome preservation","volume":"114","author":"Akiyama","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1046\/j.1365-2958.1997.3411711.x","article-title":"Microbial pathogenesis in cystic fibrosis: Co-ordinate regulation of heat-shock response and conversion to mucoidy in Pseudomonas aeruginosa","volume":"24","author":"Schurr","year":"1997","journal-title":"Mol. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6677","DOI":"10.1128\/jb.176.21.6677-6687.1994","article-title":"Mucoid-to-nonmucoid conversion in alginate-producing Pseudomonas aeruginosa often results from spontaneous mutations in algT, encoding a putative alternate sigma factor, and shows evidence for autoregulation","volume":"176","author":"DeVries","year":"1994","journal-title":"J. Bacteriol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1128\/jb.175.4.1153-1164.1993","article-title":"Characterization of a locus determining the mucoid status of Pseudomonas aeruginosa: AlgU shows sequence similarities with a Bacillus sigma factor","volume":"175","author":"Martin","year":"1993","journal-title":"J. Bacteriol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.1128\/jb.179.11.3711-3720.1997","article-title":"Posttranslational control of the algT (algU)-encoded sigma22 for expression of the alginate regulon in Pseudomonas aeruginosa and localization of its antagonist proteins MucA and MucB (AlgN)","volume":"179","author":"Mathee","year":"1997","journal-title":"J. Bacteriol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4237","DOI":"10.1128\/IAI.02014-05","article-title":"Identification of Pseudomonas aeruginosa genes involved in virulence and anaerobic growth","volume":"74","author":"Filiatrault","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1128\/AAC.00507-08","article-title":"Novel genetic determinants of low-level aminoglycoside resistance in Pseudomonas aeruginosa","volume":"52","author":"Schurek","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5642","DOI":"10.1128\/jb.175.17.5642-5647.1993","article-title":"Escherichia coli mutants lacking NADH dehydrogenase I have a competitive disadvantage in stationary phase","volume":"175","author":"Zambrano","year":"1993","journal-title":"J. Bacteriol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Amini, S., Hottes, A.K., Smith, L.E., and Tavazoie, S. (2011). Fitness landscape of antibiotic tolerance in Pseudomonas aeruginosa biofilms. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002298"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1126\/science.1238328","article-title":"Fe-S cluster biosynthesis controls uptake of aminoglycosides in a ROS-less death pathway","volume":"340","author":"Ezraty","year":"2013","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3928","DOI":"10.1038\/s41598-018-22300-1","article-title":"Structural and functional studies on Pseudomonas aeruginosa DspI: Implications for its role in DSF biosynthesis","volume":"8","author":"Liu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1128\/JB.01214-08","article-title":"A fatty acid messenger is responsible for inducing dispersion in microbial biofilms","volume":"191","author":"Davies","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Feinbaum, R.L., Urbach, J.M., Liberati, N.T., Djonovic, S., Adonizio, A., Carvunis, A.R., and Ausubel, F.M. (2012). Genome-wide identification of Pseudomonas aeruginosa virulence-related genes using a Caenorhabditis elegans infection model. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002813"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1046\/j.1365-2958.2000.01741.x","article-title":"Lipopolysaccharide core phosphates are required for viability and intrinsic drug resistance in Pseudomonas aeruginosa","volume":"35","author":"Walsh","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e00280-20","DOI":"10.1128\/JB.00280-20","article-title":"Functional Characterization of the Pseudomonas aeruginosa Ribosome Hibernation-Promoting Factor","volume":"202","author":"Franklin","year":"2020","journal-title":"J. Bacteriol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Theng, S., Williamson, K.S., and Franklin, M.J. (2020). Role of Hibernation Promoting Factor in Ribosomal Protein Stability during Pseudomonas aeruginosa Dormancy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249494"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/mmi.14001","article-title":"Expression and regulation of the Pseudomonas aeruginosa hibernation promoting factor","volume":"110","author":"Akiyama","year":"2018","journal-title":"Mol. Microbiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e0022421","DOI":"10.1128\/JB.00224-21","article-title":"Cautionary Notes on the Use of Arabinose- and Rhamnose-Inducible Expression Vectors in Pseudomonas aeruginosa","volume":"203","author":"McMackin","year":"2021","journal-title":"J. Bacteriol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.bbagen.2009.06.005","article-title":"Protein aggregation as a paradigm of aging","volume":"1790","author":"Lindner","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1146\/annurev-micro-041320-111014","article-title":"Metabolic Reprogramming and Longevity in Quiescence","volume":"76","author":"Dworkin","year":"2022","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4327","DOI":"10.1128\/JB.187.13.4327-4337.2005","article-title":"Calcium-induced virulence factors associated with the extracellular matrix of mucoid Pseudomonas aeruginosa biofilms","volume":"187","author":"Sarkisova","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1128\/JB.00963-15","article-title":"The Pseudomonas aeruginosa PAO1 two-component regulator CarSR regulates calcium homeostasis and calcium-iInduced virulence factor production through Its regulatory targets CarO and CarP","volume":"198","author":"Guragain","year":"2016","journal-title":"J. Bacteriol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6387","DOI":"10.1128\/JB.01479-12","article-title":"Sequence-verified two-allele transposon mutant library for Pseudomonas aeruginosa PAO1","volume":"194","author":"Held","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_83","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_84","unstructured":"Blazejczyk, M., Miron, M., and Nadon, R. (2014, September 15). FlexArray: A statistical data analysis software for gene expression microarrays. Genome Que. Montr. Can., Available online: http:\/\/genomequebecmcgillca\/FlexArray."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Sherman","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"W169","DOI":"10.1093\/nar\/gkm415","article-title":"DAVID Bioinformatics Resources: Expanded annotation database and novel algorithms to better extract biology from large gene lists","volume":"35","author":"Huang","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_87","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."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nprot.2007.521","article-title":"Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances","volume":"3","author":"Wiegand","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nmeth.1818","article-title":"HHblits: Lightning-fast iterative protein sequence searching by HMM-HMM alignment","volume":"9","author":"Remmert","year":"2011","journal-title":"Nat. Methods"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"D412","DOI":"10.1093\/nar\/gkaa913","article-title":"Pfam: The protein families database in 2021","volume":"49","author":"Mistry","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"van Kempen, M., Kim, S., Tumescheit, C., Mirdita, M., Gilchrist, C.L.M., S\u00f6ding, J., and Steinegger, M. (2022). Foldseek: Fast and accurate protein structure search. bioRxiv.","DOI":"10.1101\/2022.02.07.479398"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1513\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:04:37Z","timestamp":1760119477000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1513"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,12]]},"references-count":91,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24021513"],"URL":"https:\/\/doi.org\/10.3390\/ijms24021513","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,12]]}}}