The function of wzy_K1 (magA), the serotype K1 polymerase gene in Klebsiella pneumoniae cps gene cluster.

Received 18 February 2009; accepted 18 February 2009; electronically published 12 March 2010. Potential conflicts of interest: All authors report no potential conflicts. Reprints or correspondence: Dr Chi-Tai Fang, Div of Infectious Diseases, Dept of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan S Rd, Taipei, Taiwan (fangct@ntu.edu .tw). The Journal of Infectious Diseases 2010;201 :1268–1269 2010 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2010/20108-0023$15.00 DOI: 10.1086/652183 In this issue of the Journal, Yeh et al [1] revisit the importance of magA in Klebsiella pneumoniae causing pyogenic liver abscess, as well as its exact role in serotype K1 capsule formation. The mucoviscosityassociated gene A (magA) of K. pneumoniae was originally discovered in 2002 by me and my colleagues [2, 3] in tissueinvasive K. pneumoniae strains causing primary liver abscess complicated by metastatic meningitis or endophthalmitis, during the search for a good molecular marker for this type of highly virulent pathogen [2]. This previously unknown virulence gene was provisionally designated “magA” in the article published in 2004 [2], because it is associated with hypermucoviscosity phenotype, and encodes a 43-kDa outer membrane protein involved in the production of exopolysaccharide. Subsequently, sequencing of the magA flanking region revealed a capsular polysaccharides synthesis (cps) region [4]. Futher experiments proved that the operon containing magA is responsible for capsular serotype K1, with the demonstration that the mutation of magA or any of its 3 adjacent genes results in the loss of capsular serotype K1 antigenicity, which is restored by trans-complementation [4]. Using bioinformatics analysis [5], we found that magA is the serotype K1 allele of the polymerase gene wzy in the cps gene cluster [5, p 285–287], and initially described this finding in a grant proposal submitted to the Taiwan National Science Council on 22 December 2005 [6, p 15– 16]. We then sequenced and identified the corresponding wzy alleles in the cps regions of 5 of the other most common serotypes (K2, K5, K20, K54, and K57) [5] and established an original cps genotyping method that is based on polymerase chain reaction (PCR) detection of magA (wzy_K1) and the 5 corresponding wzy alleles [5]. We demonstrated a lack of PCR cross-reaction for each one of the 6 wzy genotypes with its other 76 K-serotype reference strains and confirmed that wzy genotype K1 (magA) is serotype K1 specific [5]. After determining the genotypes for 177 K. pneumoniae strains isolated from patients with pyogenic liver abscess [5], we compared the genotype K1 and nonK1 groups. We verified the important role of wzy genotype K1 (magA) in K. pneumoniae virulence and clinical outcome, respectively, showing that genotype K1 was significantly more virulent than either genotype K2 or the other genotypes and that genotype K1 was the only significant risk factor for septic ocular or central nervous system complications [5]. The entire set of experiments and analyses (including bioinformatics analysis, cps region sequencing, wzy genotyping, virulence assay, clinical outcome analysis, and risk factor identification) were reported in Clinical Infectious Diseases in 2007 in an original article entitled “Klebsiella pneumoniae Genotype K1: An Emerging Pathogen That Causes Septic Ocular or Central Nervous System Complications from Pyogenic Liver Abscess” [5]. We then officially renamed and redefined magA in the GenBank as “Klebsiella pneumoniae wzy_K1 gene for serotype K1 polymerase” with a new entry (GenBank accession number AB355924) [7], which cites our 2007 article [5]. The “features” section clearly states that “the previous name is magA; the previous name is mucoviscosity-associated protein A” and that “product p serotype K1 polymerase” [7]. These new data, also made available in the first entry (GenBank accession number AB085741) [3, 8], have been available in