Population shift in mannose-specific fimbriated phase of Klebsiella pneumoniae during experimental urinary tract infection in mice

Abstract

The infection rate (percentage of mice shedding 10(5) organisms per ml of urine) in 27 mice infected intravesicularly with a mannose-specific (MS+) phenotype of Klebsiella pneumoniae was 85% at day 7, and all the bacteria shed during the 7 days exhibited strong MS activity as estimated by a yeast aggregation assay. In contrast, the outcome of infection with an MS- phenotype of the same strain in 47 mice was heterogeneous: one group of 25 mice continued to shed the originally injected phenotype (MS-) throughout the investigation period, whereas the second group (22 mice) shed bacteria with various degrees of phenotypic conversion to MS+. In the first group, the rate of infection at day 7 was significantly reduced (28%) compared with that of the second group (68%). Mice infected with a mixture of 5% MS+ bacteria and 95% of an MS- variant which lost its ability to undergo phase variation had an infection rate of 89%, but at day 7 95% of the excreted bacteria were MS+. The infection rate of mice injected with the MS- variant was 14%, and none of the mice shed MS+ bacteria. The incidence of kidney pathology was higher in mice inoculated with the MS+ phenotype (3 of 10) or in the group in which the MS+ overgrew the MS- phenotype (4 of 10) as compared with the group of mice in which no such shift occurred (1 of 11). The kidneys of four mice which excreted mostly MS+ organisms harbored a population predominantly of the MS- phenotype. These results suggest that the MS adhesin confers an advantage in the initial steps of the infectious process in the bladder but not in later stages of infection in the kidney, emphasizing the importance of phase variation in the survival of bacteria at the various stages of the infectious process.