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 1 organisms per ml of urine) in 27 mice infected intravesicularly with a mannose-specific (MS') phenotype of KkbsieUa 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 MSphenotype of the same strain in 47 mice was heterogenous: 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.

Klebsiellaspp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors

“…In particular, animal models have been established to study Klebsiella virulence factors in UTIs; mice and rats seem to be appropriate animal types. Lower UTIs have been investigated in the diuresis mouse or rat model of cystitis by intravesicular injection of organisms (77,134). To study Klebsiella-mediated upper UTI, a rat model of experimental retrograde pyelitis has been established (78).…”

“…The relevance of these pili to bacterial virulence is thought to arise mainly from binding of the bacteria to mucus or to epithelial cells of the urogenital, respiratory, and intestinal tracts (16,162,244). Their role in the pathogenesis of UTI was clarified mostly in studies on E. coli but has also been described for K. pneumoniae in animal models (77,78,134). Although associated primarily with the pathogenesis of lower UTI (106), type 1 pili may also be involved in the pathogenesis of pyelonephritis (78,141).…”

“…Adhesin-binding triggers stimulation of the leukocyte (137), which ultimately leads to phagocytosis and intracellular killing of the bacterium (131). The bacterium counters this form of host defense by switching off the expression of type 1 pili in tissue (134). Thus, while type 1 pili are important for host colonization, their contribution to subsequent steps of pathogenesis is less clear.…”

Inability of encapsulated Klebsiella pneumoniae to assemble functional type 1 fimbriae on their surface

“…Type 1 ¢mbriae were visualized by negative staining [17]. For visualization of the capsule, we employed an immunoelectron microscopy technique with anti-K21a sera [13].…”

Adhesive properties and antibiotic resistance of Klebsiella, Enterobacter, and Serratia clinical isolates involved in nosocomial infections

“…The type 1 fimbriae of a Klebsiella sp. facilitate colonization of the urinary tract in mice and have been significantly associated with human pyelonephritis isolates (19,22). Many members of the family Enterobacteriaceae also express type 3 fimbriae, which mediate mannose-resistant, Klebsiella-like agglutination of erythrocytes treated with tannic acid.…”