The
siderophore aerobactin is the dominant
siderophore produced by hypervirulent Klebsiella pneumoniae (hvKP) and was previously shown to be a major
virulence factor in systemic
infection. However, strains of hvKP commonly produce the additional
siderophores yersiniabactin,
salmochelin, and
enterobactin. The roles of these
siderophores in hvKP
infection have not been optimally defined. To that end, site-specific gene disruptions were created in hvKP1 (wild type), resulting in the generation of hvKP1ΔiucA (
aerobactin deficient), hvKP1ΔiroB (
salmochelin deficient), hvKP1ΔentB (
enterobactin and
salmochelin deficient), hvKP1Δirp2 (
yersiniabactin deficient), and hvKP1ΔentBΔirp2 (
enterobactin,
salmochelin, and
yersiniabactin deficient). The growth/survival of these constructs was compared to that of their wild-type parent hvKP1 ex vivo in human
ascites fluid, human serum, and human urine and in vivo in mouse systemic
infection and pulmonary challenge models. Interestingly, in contrast to
aerobactin, the inability to produce
enterobactin,
salmochelin, or
yersiniabactin individually or in combination did not decrease the ex vivo growth/survival in human
ascites or serum or decrease virulence in the in vivo
infection models. Surprisingly, none of the
siderophores increased growth in human urine. In human
ascites fluid supplemented with exogenous
siderophores,
siderophores increased the growth of hvKP1ΔiucA, with the relative activity being
enterobactin >
aerobactin >
yersiniabactin >
salmochelin, suggesting that the contribution of
aerobactin to virulence is dependent on both innate
biologic activity and quantity produced. Taken together, these data confirm and extend a role for
aerobactin as a critical
virulence factor for hvKP. Since it appears that
aerobactin production is a defining trait of hvKP strains, this factor is a potential antivirulence target.