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Possible role of L-form switching in recurrent urinary tract infection
Katarzyna M Mickiewicz1, Yoshikazu Kawai2, Lauren Drage2
1The Centre for Bacterial Cell Biology, The Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Baddiley-Clark Building, Newcastle upon Tyne, NE2 4AX, UK. katarzyna.mickiewicz@ncl.ac.uk.
Abstract:
Recurrent urinary tract infection (rUTI) is a major medical problem, especially in the elderly and infirm, but the nature of the reservoir of organisms responsible for survival and recolonisation after antibiotic treatment in humans is unclear. Here, we demonstrate the presence of cell-wall deficient (L-form) bacteria in fresh urine from 29 out of 30 older patients with rUTI. In urine, E. coli strains from patient samples readily transition from the walled state to L-form during challenge with a cell wall targeting antibiotic. Following antibiotic withdrawal, they then efficiently transition back to the walled state. E. coli switches between walled and L-form states in a zebrafish larva infection model. The results suggest that L-form switching is a physiologically relevant phenomenon that may contribute to the recurrence of infection in older patients with rUTI, and potentially other infections.
Insights
Cell-wall deficient bacteria, or L-form bacteria, were found in most elderly patients with recurrent urinary tract infections (rUTI). These L-form bacteria may explain why rUTI persists after antibiotic treatment.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Recurrent urinary tract infections (rUTI) pose a significant health challenge, particularly for the elderly.
- The reservoir for bacteria causing rUTI and enabling recolonization post-antibiotic therapy remains poorly understood.
Purpose of the Study:
- To investigate the presence and role of cell-wall deficient (L-form) bacteria in elderly patients with rUTI.
- To explore the transition dynamics between walled and L-form states of bacteria in response to antibiotics.
Main Methods:
- Detection of L-form bacteria in urine samples from patients with rUTI.
- Experimental induction of L-form transition in E. coli strains using cell wall-targeting antibiotics.
- Observation of bacterial state switching in a zebrafish larva infection model.
Main Results:
- Cell-wall deficient (L-form) bacteria were identified in urine from 29 out of 30 elderly patients with rUTI.
- E. coli strains demonstrated facile transition to L-form under antibiotic pressure and efficiently reverted to the walled state upon antibiotic withdrawal.
- Bacterial switching between walled and L-form states was confirmed in a zebrafish infection model.
Conclusions:
- L-form bacterial switching is a physiologically relevant phenomenon in the context of rUTI.
- This switching mechanism may contribute to the persistence and recurrence of urinary tract infections in the elderly.
- The findings suggest L-form bacteria could be implicated in other recurrent infections.
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