{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:01:34Z","timestamp":1793149294780,"version":"4.5.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hypervirulent <jats:italic>Klebsiella pneumoniae<\/jats:italic> produce an increased amount of capsular substance and are associated with a hypermucoviscous phenotype. Capsule production is regulated by capsular regulatory genes and capsular gene cluster variations. In the present study, we focus on the effect of <jats:italic>rmpA<\/jats:italic> and <jats:italic>wcaJ<\/jats:italic>on capsule biosynthesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Phylogenetic trees were constructed to analyze wcaJ and rmpA sequence diversity in different serotypes hypervirulent strains. Then mutant strains (K2044<jats:sup>\u0394wcaJ<\/jats:sup>, K2044<jats:sup>K1wcaJ<\/jats:sup>, K2044<jats:sup>K2wcaJ<\/jats:sup>and K2044<jats:sup>K64wcaJ<\/jats:sup>) were used to verify the effects of wcaJ and its diversity on capsule synthesis and strain virulence. Furthmore, the role of rmpA in capsular synthesis and its mechanisms were detected in K2044<jats:sup>\u0394rmpA<\/jats:sup> strain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RmpA sequences are conversed in different serotypes. And rmpA promoted the production of hypercapsules by simultaneously acting on three promoters in cps cluster. Whereas w<jats:italic>caJ<\/jats:italic>, its sequences are different in different serotypes, and its loss result in the termination of capsular synthesis. Moreover, the results verified that K2 <jats:italic>wcaJ<\/jats:italic> could form hypercapsule in K2044 strains (K1 serotype), but K64 w<jats:italic>caJ<\/jats:italic> could not.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The interaction of multiple factors is involved in capsule synthesis, including w<jats:italic>caJ<\/jats:italic> and r<jats:italic>mpA<\/jats:italic>. RmpA, an known conserved capsular regulator gene, acts on cps cluster promoters to promote the production of the hypercapsule. WcaJ as initiating enzyme of CPS biosynthesis, its presence determines the synthesis of capsule. Besides, different from rmpA, w<jats:italic>caJ<\/jats:italic> sequence consistency is limited to the same serotype, which cause wcaJ functioning in different serotype strains with sequence recognition specificity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1108818","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T05:05:59Z","timestamp":1682399159000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: \u201cdirect\u201d wcaJ variation vs. \u201cindirect\u201d rmpA regulation"],"prefix":"10.3389","volume":"13","author":[{"given":"Weiwen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxing","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dakang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1080\/21505594.2015.1030101","article-title":"Klebsiella pneumoniae and the pyogenic liver abscess: implications and association of the presence of rpmA genes and expression of hypermucoviscosity","volume":"6","author":"Alc\u00e1ntar-Curiel","year":"2015","journal-title":"Virulence"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1128\/iai.59.6.2043-2050.1991","article-title":"Biosynthesis of klebsiella K2 capsular polysaccharide in escherichia coli HB101 requires the functions of rmpA and the chromosomal cps gene cluster of the virulent strain klebsiella pneumoniae chedid (O1:K2)","volume":"59","author":"Arakawa","year":"1991","journal-title":"Infect. Immun."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00775-15","article-title":"Genome-wide identification of klebsiella pneumoniae fitness genes during lung infection","volume":"6","author":"Bachman","year":"2015","journal-title":"mBio"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.872155","article-title":"What is IL-1 for? the functions of interleukin-1 across evolution","volume":"13","author":"Boraschi","year":"2022","journal-title":"Front. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.str.2013.03.010","article-title":"Wzi is an outer membrane lectin that underpins group 1 capsule assembly in escherichia coli","volume":"21","author":"Bushell","year":"2013","journal-title":"Structure. (London. Engl. 1993)."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1080\/21505594.2017.1317412","article-title":"Hypervirulence and hypermucoviscosity: Two different but complementary klebsiella spp. phenotypes","volume":"8","author":"Catal\u00e1n-N\u00e1jera","year":"2017","journal-title":"Virulence"},{"key":"B7","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.gene.2004.05.008","article-title":"Sequencing and analysis of the large virulence plasmid pLVPK of klebsiella pneumoniae CG43","volume":"337","author":"Chen","year":"2004","journal-title":"Gene"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.637018","article-title":"Identification of microbiome etiology associated with drug resistance in pleural empyema","volume":"11","author":"Chen","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"6640","DOI":"10.1073\/pnas.120163297","article-title":"One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products","volume":"97","author":"Datsenko","year":"2000","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B10","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/s41591-020-0825-4","article-title":"Adaptive evolution of virulence and persistence in carbapenem-resistant klebsiella pneumoniae","volume":"26","author":"Ernst","year":"2020","journal-title":"Nat. Med."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000073","article-title":"Klebsiella pneumoniaeThe diversity of surface polysaccharides","volume":"2","author":"Follador","year":"2016","journal-title":"Microb. Genomics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1136\/gut.50.3.420","article-title":"A global emerging disease of klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis","volume":"50","author":"Fung","year":"2002","journal-title":"Gut"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1038\/labinvest.2011.52","article-title":"Immune response and pathophysiological features of klebsiella pneumoniae liver abscesses in an animal model","volume":"91","author":"Fung","year":"2011","journal-title":"Lab. Invest."},{"key":"B14","doi-asserted-by":"publisher","first-page":"100891","DOI":"10.1016\/j.drup.2022.100891","article-title":"Opposite evolution of pathogenicity driven by in vivo wzc and wcaJ mutations in ST11-KL64 carbapenem-resistant klebsiella pneumoniae","volume":"66","author":"He","year":"2023","journal-title":"Drug Resistance. Updates. Rev. Commentaries. Antimicrob. Anticancer Chemother."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010693","article-title":"Capsule type defines the capability of klebsiella pneumoniae in evading kupffer cell capture in the liver","volume":"18","author":"Huang","year":"2022","journal-title":"PloS Pathog."},{"key":"B16","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1128\/iai.63.3.847-852.1995","article-title":"Relationships among capsular structure, phagocytosis, and mouse virulence in klebsiella pneumoniae","volume":"63","author":"Kabha","year":"1995","journal-title":"Infect. Immun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jgar.2021.02.020","article-title":"A global perspective on the convergence of hypervirulence and carbapenem resistance in klebsiella pneumoniae","volume":"25","author":"Lan","year":"2021","journal-title":"J. Global Antimicrob. Resistance."},{"key":"B18","doi-asserted-by":"publisher","first-page":"29316","DOI":"10.1038\/srep29316","article-title":"Differential host susceptibility and bacterial virulence factors driving klebsiella liver abscess in an ethnically diverse population","volume":"6","author":"Lee","year":"2016","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009376","article-title":"A systematic analysis of hypermucoviscosity and capsule reveals distinct and overlapping genes that impact klebsiella pneumoniae fitness","volume":"17","author":"Mike","year":"2021","journal-title":"PloS Pathog."},{"key":"B20","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1128\/iai.40.1.56-61.1983","article-title":"Virulence for mice of klebsiella strains belonging to the O1 group: relationship to their capsular (K) types","volume":"40","author":"Mizuta","year":"1983","journal-title":"Infect. Immun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1128\/MMBR.00078-15","article-title":"Klebsiella pneumoniae: Going on the offense with a strong defense","volume":"80","author":"Paczosa","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev. MMBR."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-19","article-title":"Hypervirulent klebsiella pneumoniae","volume":"32","author":"Russo","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00776-18","article-title":"Identification of biomarkers for differentiation of hypervirulent klebsiella pneumoniae from classical k. pneumoniae","volume":"56","author":"Russo","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"107","DOI":"10.4161\/viru.22718","article-title":"Hypervirulent (hypermucoviscous) klebsiella pneumoniae: a new and dangerous breed","volume":"4","author":"Shon","year":"2013","journal-title":"Virulence"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4170","DOI":"10.1099\/mic.0.029017-0","article-title":"Genetic diversity of capsular polysaccharide biosynthesis in klebsiella pneumoniae clinical isolates","volume":"155","author":"Shu","year":"2009","journal-title":"Microbiol. (Reading)."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00630-15","article-title":"Mapping the evolution of hypervirulent klebsiella pneumoniae","volume":"6","author":"Struve","year":"2015","journal-title":"mBio"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1080\/22221751.2022.2103454","article-title":"Klebsiella pneumoniaePrevalence of hypervirulent and carbapenem-resistant under divergent evolutionary patterns","volume":"11","author":"Tian","year":"2022","journal-title":"Emerging. Microbes Infect."},{"key":"B28","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.mib.2020.01.006","article-title":"The intersection of capsule gene expression, hypermucoviscosity and hypervirulence in klebsiella pneumoniae","volume":"54","author":"Walker","year":"2020","journal-title":"Curr. Opin. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00089-19","article-title":"A klebsiella pneumoniae regulatory mutant has reduced capsule expression but retains hypermucoviscosity","volume":"10","author":"Walker","year":"2019","journal-title":"mBio"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01750-20","article-title":"The small protein RmpD drives hypermucoviscosity in klebsiella pneumoniae","volume":"11","author":"Walker","year":"2020","journal-title":"mBio"},{"key":"B31","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1146\/annurev.biochem.75.103004.142545","article-title":"Biosynthesis and assembly of capsular polysaccharides in escherichia coli","volume":"75","author":"Whitfield","year":"2006","journal-title":"Annu. Rev. Biochem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1016\/j.carres.2003.08.010","article-title":"Biosynthesis and assembly of group 1 capsular polysaccharides in escherichia coli and related extracellular polysaccharides in other bacteria","volume":"338","author":"Whitfield","year":"2003","journal-title":"Carbohydr. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1046\/j.1365-2958.1999.01276.x","article-title":"Structure, assembly and regulation of expression of capsules in escherichia coli","volume":"31","author":"Whitfield","year":"1999","journal-title":"Mol. Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1080\/21505594.2021.1960101","article-title":"K. pneumoniaeThe hypermucoviscosity of hypervirulent confers the ability to evade neutrophil-mediated phagocytosis","volume":"12","author":"Xu","year":"2021","journal-title":"Virulence"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.diagmicrobio.2008.04.007","article-title":"Comparison of prevalence of virulence factors for klebsiella pneumoniae liver abscesses between isolates with capsular K1\/K2 and non-K1\/K2 serotypes","volume":"62","author":"Yu","year":"2008","journal-title":"Diagn. Microbiol. Infect. Dis."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1108818\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T05:06:20Z","timestamp":1682399180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1108818\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,25]]},"references-count":35,"alternative-id":["10.3389\/fcimb.2023.1108818"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1108818","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,25]]},"article-number":"1108818"}}