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J Med Microbiol 55 (2006), 803-804; DOI: 10.1099/jmm.0.46368-0
© 2006 Society for General Microbiology
ISSN 1473-5644

Correspondence

magA is not a specific virulence gene for Klebsiella pneumoniae strains causing liver abscess but is part of the capsular polysaccharide gene cluster of K. pneumoniae serotype K1

Kuo-Ming Yeh1,2, Feng-Yee Chang1, Chang-Phone Fung3, Jung-Chung Lin1 and L. K. Siu4

1 Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taiwan

2 Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan

3 Section of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan

4 Division of Clinical Research, National Health Research Institutes, NDMC, Min-Chuan East Rd, Neihu, Taipei, Taiwan

Correspondence
L. K. Siu
(lksiu{at}nhri.org.tw)


Klebsiella pneumoniae is an important emerging pathogen in community-acquired liver abscesses worldwide, especially in Taiwan, Asia and the USA (Chang & Chou, 1995; Okano et al., 2002; Lim et al., 2003; Lederman & Crum, 2005). The prevalence of K. pneumoniae in cases of pyogenic liver abscess is as high as 78 % in Taiwan and 41 % in the USA (Tsay et al., 2002; Rahimian et al., 2004). Our group has observed that among our K. pneumoniae liver abscess cases, 85 of 134 (63.4 %) were caused by serotype K1 K. pneumoniae and 12 of the 14 (85.7 %) cases with complications of endophthalmitis were serotype K1, including K1 isolates which are highly resistant to neutrophil phagocytosis (Fung et al., 2002; Lin et al., 2004).

Further investigation by Fang et al. (2004) has identified a novel virulence gene, magA, that causes K. pneumoniae liver abscess and septic metastatic complications. Among the isolates in Fang's study, 52 of 53 (98 %) liver abscess isolates carried this specific virulence gene and the presence of one magA-negative isolate was suggested to be due to the patient's underlying disease of liver cirrhosis and hepatic failure. Thus Fang et al. (2004) concluded that magA is an essential virulence gene for K. pneumoniae strains causing liver abscess and could be used as a diagnostic tool. Unfortunately, the authors did not discuss the correlation of virulence between the novel gene and serotype specificity.

In a recent article in the Journal of Medical Microbiology, Struve et al. (2005) tried to investigate the above correlation and found that, of the 495 Klebsiella isolates from a worldwide collection isolated from unknown different sites, all 39 magA-positive isolates were of serotype K1 and none of the 456 non-K1 serotypes contained magA. They concluded that magA is restricted to the capsular gene cluster of serotype K1. Since all the 495 isolates were non-liver abscess isolates, the presence of magA in non-K1 liver abscess isolates has not been studied. One may argue that all liver abscess isolates may have the magA virulence gene. Our group has sequenced the whole K1 capsular gene cluster (GenBank accession no. AY762939; Fig. 1Go). Thus we have tried to investigate the prevalence of magA among serotypes K1, K2 and other serotypes from liver abscess patients. Our results further confirmed those of Struve et al. (2005) indicating that magA is only present in serotype K1 liver and non-liver abscess isolates.


Figure 1
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  		Fig. 1. Gene cluster for K1 capsular polysaccharide (GenBank accession no. AY762939), showing genes with known and unknown functions.

 
In the present study, we investigated the incidence of magA among 134 K. pneumoniae liver abscess isolates (Fung et al., 2002) and 4 strains of K. pneumoniae from the ATCC. Nested PCRs for magA detection were designed according to Fang et al. (2004). The sequence of the two primer sets were as follows: outer forward 5'-GGTGCTCTTTACATCATTGC-3' and outer reverse 5'-GCAATGGCCATTTGCGTAAG-3'; and inner forward 5'-CGCCGCAAATACGAGAAGTG-3' and inner reverse 5'-GCAATCGAAGTGAAGAGTGC. Control strains of serotype K1 (ATCC 4208), K2 (ATCC 9997), K3 (ATCC 13883) and K6 (ATCC 700603) were included for PCR. Results obtained from PCR amplification showed that only K1 isolates were positive for magA (Table 1Go). All other capsular serotypes were negative for magA. Thus we strongly agree with Struve et al. (2005) that the K1 capsule rather than magA is the important virulence factor for K. pneumoniae strains causing liver abscess and that magA is a part of the gene cluster involved in K1 capsule formation. According to studies done on our collection of K. pneumoniae liver abscess isolates, more than 36 % of the cases would have been missed if magA was used as a diagnostic tool. Although 86 % of the cases with complications were caused by serotype K1 and tested positive for magA, only 14 cases were collected in our previous study (Fung et al., 2002). The usefulness of magA for the detection of liver abscess and septic metastatic complications needs to be studied further.


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  		Table 1. PCR amplification of magA among different K serotypes of K. pneumoniae isolated from liver abscess patients

 
We conclude that magA is a component of K1 capsule formation, but is not an independent virulence gene in K. pneumoniae strains causing liver abscess. The K1 capsule rather than magA is an important virulence factor.

Acknowledgements

This work is supported by a grant from the National Science Council (NSC94-2320-B-400-002).

REFERENCES

Chang, F. Y. & Chou, M. Y. (1995). Comparison of pyogenic liver abscesses caused by Klebsiella pneumoniae and non-K. pneumoniae pathogens. J Formos Med Assoc 94, 232–237.[Medline]

Fang, C. T., Chuang, Y. P., Shun, C. T., Chang, S. C. & Wang, J. T. (2004).A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J Exp Med 199, 697–705.[Abstract/Free Full Text]

Fung, C. P., Chang, F. Y., Lee, S. C., Hu, B. S., Kuo, B. I., Liu, C. Y., Ho, M. & Siu, L. K. (2002). A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis? Gut 50, 420–424.[Abstract/Free Full Text]

Lederman, E. R. & Crum, N. F. (2005). Pyogenic liver abscess with a focus on Klebsiella pneumoniae as a primary pathogen: an emerging disease with unique clinical characteristics. Am J Gastroenterol 100, 322–331.[CrossRef][Medline]

Lim, S. W., Lee, E. J., Lee, S. W., Kim, S. M., Kim, J. H., Kim, B. J., Jang, B. I., Kim, T. N. & Chung, M. K. (2003). [Clinical significance of Klebsiella pneumoniae in liver abscess]. Korean J Gastroenterol 42, 226–231.[Medline]

Lin, J. C., Chang, F. Y., Fung, C. P., Xu, J. Z., Cheng, H. P., Wang, J. J., Huang, L. Y. & Siu, L. K. (2004). High prevalence of phagocytic-resistant capsular serotypes of Klebsiella pneumoniae in liver abscess. Microbes Infect 6, 1191–1198.[CrossRef][Medline]

Okano, H., Shiraki, K., Inoue, H. & 8 other authors (2002). Clinicopathological analysis of liver abscess in Japan. Int J Mol Med 10, 627–630.[Medline]

Rahimian, J., Wilson, T., Oram, V. & Holzman, R. S. (2004). Pyogenic liver abscess: recent trends in etiology and mortality. Clin Infect Dis 39, 1654–1659.[CrossRef][Medline]

Struve, C., Bojer, M., Nielsen, E. M., Hansen, D. S. & Krogfelt, K. A. (2005). Investigation of the putative virulence gene magA in a worldwide collection of 495 Klebsiella isolates: magA is restricted to the gene cluster of Klebsiella pneumoniae capsule serotype K1. J Med Microbiol 54, 1111–1113.[Free Full Text]

Tsay, R. W., Siu, L. K., Fung, C. P. & Chang, F. Y. (2002). Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection: risk factor for mortality and the impact of capsular serotypes as a herald for community-acquired infection. Arch Intern Med 162, 1021–1027.[Abstract/Free Full Text]




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