{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:06:38Z","timestamp":1791299198552,"version":"4.1.0"},"reference-count":39,"publisher":"Microbiology Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,4,1]]},"abstract":"Clinical isolates of Pseudomonas aeruginosa<\/jats:italic> that hyperproduce a dark-brown pigment are quite often found in the lungs of chronically infected patients, suggesting that they may have an adaptive advantage in chronic infections. We have screened a library of random transposon insertions in P. aeruginosa<\/jats:italic>. Transposon insertions resulting in the hyperproduction of a dark-brown pigment were found to be located in the hmgA<\/jats:italic> gene, which putatively encodes the enzyme homogentisate-1,2-dioxygenase. Complementation studies indicate that hmgA<\/jats:italic> disruption is responsible for the hyperproduction of pyomelanin in both laboratory and clinical isolates. A relationship between hmgA<\/jats:italic> disruption and adaptation to chronic infection was explored and our results show that the inactivation of hmgA<\/jats:italic> produces a slight reduction of killing ability in an acute murine model of lung infection. On the other hand, it also confers decreased clearance and increased persistence in chronic lung infections. Whether pyomelanin production is the cause of the increased adaptation to chronicity or just a side effect of hmgA<\/jats:italic> inactivation is a question to be studied in future; however, this adaptation is consistent with the higher resistance to oxidative stress conferred in vitro<\/jats:italic> by the pyomelanin pigment. Our results clearly demonstrate that hmgA<\/jats:italic> inactivation leads to a better adaptation to chronic infection, and strongly suggest that this mechanism may be exploited in naturally occurring P. aeruginosa<\/jats:italic> strains.<\/jats:p>","DOI":"10.1099\/mic.0.024745-0","type":"journal-article","created":{"date-parts":[[2009,3,31]],"date-time":"2009-03-31T07:52:51Z","timestamp":1238485971000},"page":"1050-1057","source":"Crossref","is-referenced-by-count":129,"title":["Inactivation of the hmgA gene of Pseudomonas aeruginosa leads to pyomelanin hyperproduction, stress resistance and increased persistence in chronic lung infection"],"prefix":"10.1099","volume":"155","author":[{"given":"Alexandro","family":"Rodr\u00edguez-Rojas","sequence":"first","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), C\/ Darwin 3, Campus UAM, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Mena","sequence":"additional","affiliation":[{"name":"Servicio de Microbiologia, Hospital Son Dureta, C\/ Andrea Doria 55, 07014 Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soledad","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), C\/ Darwin 3, Campus UAM, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Borrell","sequence":"additional","affiliation":[{"name":"Servicio de Microbiologia, Hospital Son Dureta, C\/ Andrea Doria 55, 07014 Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Oliver","sequence":"additional","affiliation":[{"name":"Servicio de Microbiologia, Hospital Son Dureta, C\/ Andrea Doria 55, 07014 Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), C\/ Darwin 3, Campus UAM, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.1128\/JB.186.15.5062-5077.2004","article-title":"The homogentisate pathway: a central catabolic pathway involved in the degradation of l-phenylalanine, l-tyrosine, and 3-hydroxyphenylacetate in Pseudomonas putida","volume":"186","author":"Arias-Barrau","year":"2004","journal-title":"J Bacteriol"},{"key":"R2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/clinids\/5.2.279","article-title":"Infections caused by Pseudomonas aeruginosa","volume":"5","author":"Bodey","year":"1983","journal-title":"Rev Infect Dis"},{"key":"R3","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1128\/jb.184.4.952-961.2002","article-title":"Identification of virulence genes in a pathogenic strain of Pseudomonas aeruginosa by representational difference analysis","volume":"184","author":"Choi","year":"2002","journal-title":"J Bacteriol"},{"key":"R4","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1128\/AEM.60.8.3006-3010.1994","article-title":"Homogentisic acid is the product of MelA, which mediates melanogenesis in the marine bacterium Shewanella colwelliana D","volume":"60","author":"Coon","year":"1994","journal-title":"Appl Environ Microbiol"},{"key":"R5","volume-title":"Basic Research and Clinical Aspects of Pseudomonas aeruginosa","author":"Doring","year":"1987"},{"key":"R6","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/jac\/dkn044","article-title":"Increased mutability of Pseudomonas aeruginosa in biofilms","volume":"61","author":"Driffield","year":"2008","journal-title":"J Antimicrob Chemother"},{"key":"R7","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1111\/j.1462-2920.2003.00518.x","article-title":"Genome mosaicism is conserved but not unique in Pseudomonas aeruginosa isolates from the airways of young children with cystic fibrosis","volume":"5","author":"Ernst","year":"2003","journal-title":"Environ Microbiol"},{"key":"R8","first-page":"399","article-title":"The role of reactive oxygen species (ROS) in the effector mechanisms of human antimycobacterial immunity","volume":"43","author":"Fazal","year":"1997","journal-title":"Biochem Mol Biol Int"},{"key":"R9","volume-title":"Pathogenesis and disease. 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