Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary pyogenic liver abscess and metastatic infection

Abstract

Background. Primary pyogenic liver abscess (PLA) with septic complication by Klebsiella pneumoniae is an emerging infectious disease. Methods and results. Using DNA microarray hybridization, we identified a 20-kb chromosomal region that contained 15 open-reading frames (ORFs), including an iron-uptake system (kfu), a phosphoenolpyruvate sugar phosphotransferase system (PTS), and 6 unknown ORFs. The region was more prevalent among tissue-invasive strains (35/46) than among noninvasive strains (19/98) (P < .0001, χ2 test). To test the role played by this region in pathogenesis, 3 different deletion mutants (NTUH-K2044 [Δkfu], K2044 [ΔORF7-9], and K2044 [ΔPTS]) were constructed. Only the ΔkfuABC mutants showed decreased virulence in mice, compared with the wild-type strain. An in vitro assay confirmed the involvement of kfu in iron acquisition. There was a high correlation rate (85%) between the kfu/PTS region and 2 tissue invasion-associated chromosomal regions (allS and magA). Moreover, all 3 regions were present in strains that caused PLA plus endophthalmitis or meningitis. Conclusion. Our results suggest that chromosomal heterogeneity is present in tissue-invasive K. pneumoniae strains. A genotype containing all 3 regions is strongly associated with PLA and metastatic infection. These regions may serve as convenient markers for the rapid diagnosis of emergent tissue-invasive strains. ? 2005 by the Infectious Diseases Society of America. All rights reserved.