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Bacterial virulence versus host resistance in the urinary tracts of mice
Abstract:
The relative contributions of host resistance and bacterial virulence were analyzed in a mouse model for ascending urinary tract infection. The congenic mouse strains C3H/HeJ and C3H/HeN were used in parallel. They differ in their reactivity to lipopolysaccharide (LPS) and susceptibility to experimental urinary tract infection. C3H/HeJ cells are susceptible to infection and are nonresponders to LPS (Lpsd Lpsd), whereas C3H/HeN cells respond to LPS and are resistant to infection (Lpsn Lpsn). The Escherichia coli pyelonephritis isolate GR-12, serotype O75K5, expressing adhesins specific for globoseries glycolipids (P fimbriae) and for mannosides (type-1 fimbriae), and its derivatives deficient in these factors were used, either singly or in combination, to establish experimental infections. In C3H/HeN mice, the relative persistence of E. coli was inversely proportional to its phagocytosis in vitro. Loss of the O75 and K5 antigens increased the tendency toward hydrophobic interaction, promoted phagocytosis, and reduced persistence in the kidneys. This was not the case in C3H/HeJ mice, in which O75- and K5- serotypes persisted in the same extent as did the parent strain. The total number of bacteria recovered from the kidneys of C3H/HeJ mice was about 1,000-fold higher than the number recovered from kidneys of C3H/HeN mice 24 h after infection. Previous studies have demonstrated a delayed influx of polymorphonuclear leukocytes into the urinary tracts of C3H/HeJ mice. The results are consistent with the hypothesis that phagocyte activation through LPS is a major defense mechanism against E. coli in the kidney, a property in which C3H/HeJ mice are deficient.
Insights
Host resistance, specifically lipopolysaccharide (LPS)-mediated phagocyte activation, is crucial for controlling Escherichia coli urinary tract infections. C3H/HeJ mice, lacking LPS response, show higher bacterial persistence due to deficient immune cell activation.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Ascending urinary tract infections (UTIs) involve complex interactions between host defenses and bacterial virulence factors.
- Congenic mouse strains C3H/HeJ and C3H/HeN exhibit differential responses to lipopolysaccharide (LPS) and susceptibility to experimental UTIs.
- Escherichia coli strains with specific adhesins (P fimbriae, type-1 fimbriae) are used to model UTI pathogenesis.
Purpose of the Study:
- To elucidate the roles of host resistance and bacterial virulence in ascending urinary tract infections.
- To compare the susceptibility of C3H/HeJ (LPS non-responder) and C3H/HeN (LPS responder) mice to E. coli infection.
- To investigate the impact of bacterial adhesins on E. coli persistence and host immune response.
Main Methods:
- Utilizing congenic mouse strains C3H/HeJ and C3H/HeN to model differential LPS reactivity.
- Infecting mice with wild-type and mutant Escherichia coli strains lacking P fimbriae and type-1 fimbriae.
- Quantifying bacterial load in kidneys and assessing in vitro phagocytosis and bacterial hydrophobicity.
Main Results:
- C3H/HeJ mice, deficient in LPS response, exhibited significantly higher E. coli kidney burdens (approx. 1000-fold) compared to C3H/HeN mice.
- Loss of O75 and K5 antigens on E. coli increased hydrophobicity, enhanced phagocytosis, and reduced kidney persistence in C3H/HeN mice, but not in C3H/HeJ mice.
- Delayed polymorphonuclear leukocyte influx was observed in C3H/HeJ mice, suggesting impaired inflammatory response.
Conclusions:
- Phagocyte activation via LPS is a critical host defense mechanism against E. coli in the kidneys.
- The C3H/HeJ mouse strain's deficiency in LPS response renders it highly susceptible to E. coli UTIs.
- Bacterial factors influencing phagocytosis and host LPS-reactivity are key determinants of UTI outcome.