Yersiniabactin Is a Virulence Factor for Klebsiella pneumoniae during Pulmonary Infection

Abstract

Iron acquisition systems are essential for the in vivo growth of bacterial pathogens. Despite the epidemiological importance of Klebsiella pneumoniae, few experiments have examined the importance of siderophores in the pathogenesis of this species. A previously reported signature-tagged mutagenesis screen identified an attenuated strain that featured an insertional disruption in ybtQ, which encodes a transporter for the siderophore yersiniabactin. We used this finding as a starting point to evaluate the importance of siderophores in the physiology and pathogenesis of K. pneumoniae. Isogenic strains carrying in-frame deletions in genes required for the synthesis of either enterobactin or yersiniabactin were constructed, and the growth of these mutants was examined both in vitro and in vivo using an intranasal infection model. The results suggest divergent functions for each siderophore in different environments, with enterobactin being more important for growth in vitro under iron limitation than in vivo and the reverse being true for the yersiniabactin locus. These observations represent the first examination of isogenic mutants in iron acquisition systems for K. pneumoniae and may indicate that the acquisition of nonenterobactin siderophores is an important step in the evolution of virulent enterobacterial strains.

Comparison of virulence factors and expression of specific genes between uropathogenic Escherichia coli and avian pathogenic E. coli in a murine urinary tract infection model and a chicken challenge model

“…Iron acquisition is critical for bacteria to survive in blood or urinary tract, as these environments are iron deprived (Foxman et al, 2000). Knockout of ironacquisition genes has been shown to attenuate the virulence of many bacteria (Torres et al, 2001;Lawlor et al, 2007). Therefore, iron acquisition from the environment is essential for the pathogenesis of E. coli, and our results support this.…”

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

“…The proteins required for yersiniabactin synthesis are encoded by irp genes, and it is predicted that the transporters required for the secretion of this siderophore are encoded by the ybt and fyu genes, and the uptake receptor is encoded by ybtQ, although this remains to be thoroughly characterized in K. pneumoniae (319,321,330). Interestingly, yersiniabactin has been observed in only ϳ18% of classical but 90% of HV K. pneumoniae clinical isolates (319,329).…”

“…However, in conjunction with enterobactin, it is overrepresented in K. pneumoniae isolates from the respiratory tract (329). Notably, yersiniabactin is expressed during lung infection, and its activity is not inhibited by lipocalin-2 in vivo during early lung infection, likely because its structure significantly differs from that of enterobactin (311,321,329). This allows K. pneumoniae to grow to high bacterial loads in the lungs during infection (329).…”

Colibacillosis in poultry: unravelling the molecular basis of virulence of avian pathogenicEscherichia coliin their natural hosts

“…Apart from plasmid-borne factors, genes encoding for ferric yersiniabactin uptake (fyuA) and iron-repressible protein (irp2) have been detected by PCR in more than 65% of strains isolated from cases of avian colibacillosis (Janssen et al, 2001). Subsequent work has shown that production of yersiniabactin contributes to virulence of exPEC and Klebsiella pneumoniae in mice (Schubert et al, 2002;Lawlor et al, 2007). Additionally, chuA (encoding a haeme utilization/transport protein) was detected by screening a signature-tagged mutagenesis bank of APEC O2 in chickens (Li et al, 2005), suggesting a role in virulence.…”