{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:12:04Z","timestamp":1790255524459,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>\n              <jats:italic>Klebsiella pneumoniae<\/jats:italic> is an important opportunistic pathogen causing pneumonia, sepsis and urinary tract infections. Colonisation of the gastrointestinal (GI) tract is a key step in the development of infections; yet the specific factors important for <jats:italic>K. pneumoniae<\/jats:italic> to colonize and reside in the GI tract of the host are largely unknown. To identify <jats:italic>K. pneumoniae<\/jats:italic> genes promoting GI colonisation, a novel genomic-library-based approach was employed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Screening of a <jats:italic>K. pneumoniae<\/jats:italic> C3091 genomic library, expressed in <jats:italic>E. coli<\/jats:italic> strain EPI100, in a mouse model of GI colonisation led to the positive selection of five clones containing genes promoting persistent colonisation of the mouse GI tract. These included genes encoding the global response regulator ArcA; GalET of the galactose operon; and a cluster of two putative membrane-associated proteins of unknown function. Both ArcA and GalET are known to be involved in metabolic pathways in <jats:italic>Klebsiella<\/jats:italic> but may have additional biological actions beneficial to the pathogen. In support of this, GalET was found to confer decreased bile salt sensitivity to EPI100.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The present work establishes the use of genomic-library-based <jats:italic>in vivo<\/jats:italic> screening assays as a valuable tool for identification and characterization of virulence factors in <jats:italic>K. pneumoniae<\/jats:italic> and other bacterial pathogens.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2180-12-201","type":"journal-article","created":{"date-parts":[[2012,9,11]],"date-time":"2012-09-11T10:14:20Z","timestamp":1347358460000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Novel screening assay for in vivo selection of Klebsiella pneumoniae genes promoting gastrointestinal colonisation"],"prefix":"10.1186","volume":"12","author":[{"given":"Erik J","family":"Boll","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene N","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A","family":"Krogfelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Struve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,9,11]]},"reference":[{"issue":"4","key":"1717_CR1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1128\/CMR.11.4.589","volume":"11","author":"R Podschun","year":"1998","unstructured":"Podschun R, Ullmann U: Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev. 1998, 11 (4): 589-603.","journal-title":"Clin Microbiol Rev"},{"issue":"3","key":"1717_CR2","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s10067-006-0391-2","volume":"26","author":"A Ebringer","year":"2007","unstructured":"Ebringer A, Rashid T, Tiwana H, Wilson C: A possible link between Crohn\u2019s disease and ankylosing spondylitis via Klebsiella infections. Clin Rheumatol. 2007, 26 (3): 289-297. 10.1007\/s10067-006-0391-2.","journal-title":"Clin Rheumatol"},{"issue":"2","key":"1717_CR3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.diagmicrobio.2004.12.016","volume":"52","author":"CH Lee","year":"2005","unstructured":"Lee CH, Leu HS, Wu TS, Su LH, Liu JW: Risk factors for spontaneous rupture of liver abscess caused by Klebsiella pneumoniae. Diagn Microbiol Infect Dis. 2005, 52 (2): 79-84. 10.1016\/j.diagmicrobio.2004.12.016.","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"10","key":"1717_CR4","doi-asserted-by":"publisher","first-page":"3336","DOI":"10.1128\/JCM.00918-09","volume":"47","author":"YS Yang","year":"2009","unstructured":"Yang YS, Siu LK, Yeh KM, Fung CP, Huang SJ, Hung HC, Lin JC, Chang FY: Recurrent Klebsiella pneumoniae liver abscess: clinical and microbiological characteristics. J Clin Microbiol. 2009, 47 (10): 3336-3339. 10.1128\/JCM.00918-09.","journal-title":"J Clin Microbiol"},{"issue":"6","key":"1717_CR5","doi-asserted-by":"publisher","first-page":"684","DOI":"10.3109\/00365521.2011.560678","volume":"46","author":"IA Lee","year":"2011","unstructured":"Lee IA, Kim DH: Klebsiella pneumoniae increases the risk of inflammation and colitis in a murine model of intestinal bowel disease. Scand J Gastroenterol. 2011, 46 (6): 684-693. 10.3109\/00365521.2011.560678.","journal-title":"Scand J Gastroenterol"},{"issue":"10","key":"1717_CR6","doi-asserted-by":"publisher","first-page":"4961","DOI":"10.1128\/JCM.43.10.4961-4967.2005","volume":"43","author":"A Van\u2019t Veen","year":"2005","unstructured":"Van\u2019t Veen A, van der Zee A, Nelson J, Speelberg B, Kluytmans JA, Buiting AG: Outbreak of infection with a multiresistant Klebsiella pneumoniae strain associated with contaminated roll boards in operating rooms. J Clin Microbiol. 2005, 43 (10): 4961-4967. 10.1128\/JCM.43.10.4961-4967.2005.","journal-title":"J Clin Microbiol"},{"issue":"4","key":"1717_CR7","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1111\/j.1600-0463.2008.00922.x","volume":"116","author":"B Lytsy","year":"2008","unstructured":"Lytsy B, Sandegren L, Tano E, Torell E, Andersson DI, Melhus A: The first major extended-spectrum beta-lactamase outbreak in Scandinavia was caused by clonal spread of a multiresistant Klebsiella pneumoniae producing CTX-M-15. APMIS. 2008, 116 (4): 302-308. 10.1111\/j.1600-0463.2008.00922.x.","journal-title":"APMIS"},{"issue":"3","key":"1717_CR8","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1111\/j.1365-2672.2011.05072.x","volume":"111","author":"TP Chagas","year":"2011","unstructured":"Chagas TP, Seki LM, Cury JC, Oliveira JA, D\u00e1vila AM, Silva DM, Asensi MD: Multiresistance, beta-lactamase-encoding genes and bacterial diversity in hospital wastewater in Rio de Janeiro, Brazil. J Appl Microbiol. 2011, 111 (3): 572-581. 10.1111\/j.1365-2672.2011.05072.x.","journal-title":"J Appl Microbiol"},{"issue":"5","key":"1717_CR9","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1093\/clinids\/1.5.736","volume":"1","author":"JZ Montgomerie","year":"1979","unstructured":"Montgomerie JZ: Epidemiology of Klebsiella and hospital-associated infections. Rev Infect Dis. 1979, 1 (5): 736-753. 10.1093\/clinids\/1.5.736.","journal-title":"Rev Infect Dis"},{"issue":"12","key":"1717_CR10","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1128\/jcm.27.12.2887-2890.1989","volume":"27","author":"C De Champs","year":"1989","unstructured":"De Champs C, Sauvant MP, Chanal C, Sirot D, Gazuy N, Malhuret R, Baguet JC, Sirot J: Prospective survey of colonization and infection caused by expanded-spectrum-beta-lactamase-producing members of the family Enterobacteriaceae in an intensive care unit. J Clin Microbiol. 1989, 27 (12): 2887-2890.","journal-title":"J Clin Microbiol"},{"issue":"2","key":"1717_CR11","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1128\/iai.39.2.686-703.1983","volume":"39","author":"R Freter","year":"1983","unstructured":"Freter R, Brickner H, Fekete J, Vickerman MM, Carey KE: Survival and implantation of Escherichia coli in the intestinal tract. Infect Immun. 1983, 39 (2): 686-703.","journal-title":"Infect Immun"},{"issue":"2","key":"1717_CR12","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.resmic.2005.06.006","volume":"157","author":"N Maroncle","year":"2006","unstructured":"Maroncle N, Rich C, Forestier C: The role of Klebsiella pneumoniae urease in intestinal colonization and resistance to gastrointestinal stress. Res Microbiol. 2006, 157 (2): 184-193. 10.1016\/j.resmic.2005.06.006.","journal-title":"Res Microbiol"},{"issue":"Pt 1","key":"1717_CR13","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1099\/mic.0.25833-0","volume":"149","author":"C Struve","year":"2003","unstructured":"Struve C, Forestier C, Krogfelt KA: Application of a novel multi-screening signature-tagged mutagenesis assay for identification of Klebsiella pneumoniae genes essential in colonization and infection. Microbiology. 2003, 149 (Pt 1): 167-176.","journal-title":"Microbiology"},{"issue":"11","key":"1717_CR14","doi-asserted-by":"crossref","first-page":"6152","DOI":"10.1128\/IAI.67.11.6152-6156.1999","volume":"67","author":"S Favre-Bont\u00e9","year":"1999","unstructured":"Favre-Bont\u00e9 S, Licht TR, Forestier C, Krogfelt KA: Klebsiella pneumoniae capsule expression is necessary for colonization of large intestines of streptomycin-treated mice. Infect Immun. 1999, 67 (11): 6152-6156.","journal-title":"Infect Immun"},{"issue":"1","key":"1717_CR15","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1111\/j.1574-6968.2003.tb11511.x","volume":"218","author":"C Struve","year":"2003","unstructured":"Struve C, Krogfelt KA: Role of capsule in Klebsiella pneumoniae virulence: lack of correlation between in vitro and in vivo studies. FEMS Microbiol Lett. 2003, 218 (1): 149-154. 10.1111\/j.1574-6968.2003.tb11511.x.","journal-title":"FEMS Microbiol Lett"},{"issue":"22","key":"1717_CR16","doi-asserted-by":"publisher","first-page":"e152","DOI":"10.1093\/nar\/gkr817","volume":"39","author":"SA Nicolaou","year":"2011","unstructured":"Nicolaou SA, Gaida SM, Papoutsakis ET: Coexisting\/Coexpressing Genomic Libraries (CoGeL) identify interactions among distantly located genetic loci for developing complex microbial phenotypes. Nucleic Acids Res. 2011, 39 (22): e152-10.1093\/nar\/gkr817.","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"1717_CR17","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.ymben.2009.12.004","volume":"12","author":"JR Borden","year":"2010","unstructured":"Borden JR, Jones SW, Indurthi D, Chen Y, Papoutsakis ET: A genomic-library based discovery of a novel, possibly synthetic, acid-tolerance mechanism in Clostridium acetobutylicum involving non-coding RNAs and ribosomal RNA processing. Metab Eng. 2010, 12 (3): 268-281. 10.1016\/j.ymben.2009.12.004.","journal-title":"Metab Eng"},{"issue":"3","key":"1717_CR18","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/j.1574-695X.2010.00685.x","volume":"59","author":"SG Stahlhut","year":"2010","unstructured":"Stahlhut SG, Schroll C, Harmsen M, Struve C, Krogfelt KA: Screening for genes involved in Klebsiella pneumoniae biofilm formation using a fosmid library. FEMS Immunol Med Microbiol. 2010, 59 (3): 521-524.","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"Pt 4","key":"1717_CR19","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1099\/mic.0.28673-0","volume":"152","author":"N Hansmeier","year":"2006","unstructured":"Hansmeier N, Albersmeier A, Tauch A, Damberg T, Ros R, Anselmetti D, P\u00fchler A, Kalinowski J: The surface (S)-layer gene cspB of Corynebacterium glutamicum is transcriptionally activated by a LuxR-type regulator and located on a 6\u2009kb genomic island absent from the type strain ATCC 13032. Microbiology. 2006, 152 (Pt 4): 923-935.","journal-title":"Microbiology"},{"issue":"5","key":"1717_CR20","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/oxfordjournals.jbchem.a123947","volume":"112","author":"HL Peng","year":"1992","unstructured":"Peng HL, Fu TF, Liu SF, Chang HY: Cloning and expression of the Klebsiella pneumoniae galactose operon. J Biochem. 1992, 112 (5): 604-608.","journal-title":"J Biochem"},{"issue":"4","key":"1717_CR21","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1128\/IAI.71.4.2142-2152.2003","volume":"71","author":"AK M\u00f8ller","year":"2003","unstructured":"M\u00f8ller AK, Leatham MP, Conway T, Nuijten PJ, de Haan LA, Krogfelt KA, Cohen PS: An Escherichia coli MG1655 lipopolysaccharide deep-rough core mutant grows and survives in mouse cecal mucus but fails to colonize the mouse large intestine. Infect Immun. 2003, 71 (4): 2142-2152. 10.1128\/IAI.71.4.2142-2152.2003.","journal-title":"Infect Immun"},{"issue":"2","key":"1717_CR22","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1371\/journal.pgen.0010015","volume":"1","author":"EP Rocha","year":"2005","unstructured":"Rocha EP, Cornet E, Michel B: Comparative and evolutionary analysis of the bacterial homologous recombination systems. PLoS Genet. 2005, 1 (2): e15-10.1371\/journal.pgen.0010015.","journal-title":"PLoS Genet"},{"issue":"1","key":"1717_CR23","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1128\/jb.118.1.242-249.1974","volume":"118","author":"FN Capaldo","year":"1974","unstructured":"Capaldo FN, Ramsey G, Barbour SD: Analysis of the growth of recombination-deficient strains of Escherichia coli K-12. J Bacteriol. 1974, 118 (1): 242-249.","journal-title":"J Bacteriol"},{"issue":"9","key":"1717_CR24","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1128\/jb.176.9.2611-2618.1994","volume":"176","author":"AC Weissborn","year":"1994","unstructured":"Weissborn AC, Liu Q, Rumley MK, Kennedy EP: UTP: alpha-D-glucose-1-phosphate uridylyltransferase of Escherichia coli: isolation and DNA sequence of the galU gene and purification of the enzyme. J Bacteriol. 1994, 176 (9): 2611-2618.","journal-title":"J Bacteriol"},{"issue":"45","key":"1717_CR25","doi-asserted-by":"publisher","first-page":"43885","DOI":"10.1074\/jbc.R300025200","volume":"278","author":"HM Holden","year":"2003","unstructured":"Holden HM, Rayment I, Thoden JB: Structure and function of enzymes of the Leloir pathway for galactose metabolism. J Biol Chem. 2003, 278 (45): 43885-43888. 10.1074\/jbc.R300025200.","journal-title":"J Biol Chem"},{"issue":"4","key":"1717_CR26","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1128\/IAI.01342-06","volume":"75","author":"TD Ho","year":"2007","unstructured":"Ho TD, Waldor MK: Enterohemorrhagic Escherichia coli O157:H7\u2009gal mutants are sensitive to bacteriophage P1 and defective in intestinal colonization. Infect Immun. 2007, 75 (4): 1661-1666. 10.1128\/IAI.01342-06.","journal-title":"Infect Immun"},{"issue":"5\u20136","key":"1717_CR27","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/0923-2508(94)90092-2","volume":"145","author":"RP Gunsalus","year":"1994","unstructured":"Gunsalus RP, Park SJ: Aerobic-anaerobic gene regulation in Escherichia coli: control by the ArcAB and Fnr regulons. Res Microbiol. 1994, 145 (5\u20136): 437-450.","journal-title":"Res Microbiol"},{"issue":"10","key":"1717_CR28","doi-asserted-by":"publisher","first-page":"5583","DOI":"10.1128\/IAI.71.10.5583-5589.2003","volume":"71","author":"N Sengupta","year":"2003","unstructured":"Sengupta N, Paul K, Chowdhury R: The global regulator ArcA modulates expression of virulence factors in Vibrio cholerae. Infect Immun. 2003, 71 (10): 5583-5589. 10.1128\/IAI.71.10.5583-5589.2003.","journal-title":"Infect Immun"},{"issue":"1","key":"1717_CR29","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1128\/IAI.71.1.163-172.2003","volume":"71","author":"JA De Souza-Hart","year":"2003","unstructured":"De Souza-Hart JA, Blackstock W, Di Modugno V, Holland IB, Kok M: Two-component systems in Haemophilus influenzae: a regulatory role for ArcA in serum resistance. Infect Immun. 2003, 71 (1): 163-172. 10.1128\/IAI.71.1.163-172.2003.","journal-title":"Infect Immun"},{"issue":"10","key":"1717_CR30","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/nmeth.1701","volume":"8","author":"TN Petersen","year":"2011","unstructured":"Petersen TN, Brunak S, von Heijne G, Nielsen H: SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods. 2011, 8 (10): 785-786. 10.1038\/nmeth.1701.","journal-title":"Nat Methods"},{"issue":"9","key":"1717_CR31","doi-asserted-by":"publisher","first-page":"3476","DOI":"10.1128\/IAI.00179-11","volume":"79","author":"B Henderson","year":"2011","unstructured":"Henderson B, Martin A: Bacterial virulence in the moonlight: multitasking bacterial moonlighting proteins are virulence determinants in infectious disease. Infect Immun. 2011, 79 (9): 3476-3491. 10.1128\/IAI.00179-11.","journal-title":"Infect Immun"},{"issue":"7","key":"1717_CR32","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1128\/iai.65.7.2950-2958.1997","volume":"65","author":"TA Oelschlaeger","year":"1997","unstructured":"Oelschlaeger TA, Tall BD: Invasion of cultured human epithelial cells by Klebsiella pneumoniae isolated from the urinary tract. Infect Immun. 1997, 65 (7): 2950-2958.","journal-title":"Infect Immun"},{"issue":"9","key":"1717_CR33","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1128\/iai.64.9.3811-3817.1996","volume":"64","author":"TR Licht","year":"1996","unstructured":"Licht TR, Krogfelt KA, Cohen PS, Poulsen LK, Urbance J, Molin S: Role of lipopolysaccharide in colonization of the mouse intestine by Salmonella typhimurium studied by in situ hybridization. Infect Immun. 1996, 64 (9): 3811-3817.","journal-title":"Infect Immun"},{"key":"1717_CR34","first-page":"53","volume":"14","author":"DJ Hentges","year":"1984","unstructured":"Hentges DJ, Que JU, Casey SW, Stein AJ: The influence of streptomycin on colonization resistance in mice. Microecol Theor. 1984, 14: 53-62.","journal-title":"Microecol Theor"}],"container-title":["BMC Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2180-12-201.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T19:54:42Z","timestamp":1630526082000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmicrobiol.biomedcentral.com\/articles\/10.1186\/1471-2180-12-201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,11]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["1717"],"URL":"https:\/\/doi.org\/10.1186\/1471-2180-12-201","relation":{},"ISSN":["1471-2180"],"issn-type":[{"value":"1471-2180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,11]]},"assertion":[{"value":"21 February 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"201"}}