Mutator phenotype confers advantage in Escherichia coli chronic urinary tract infection pathogenesis

Francoise Labat1, Olivier Pradillon, Louis Garry

  • 1INSERM E0339, Faculté de Médecine Xavier Bichat, Université Paris 7, 16 rue Henri Huchard, 75018 Paris, France.

Insights

The mutator phenotype, characterized by increased mutation rates, may enhance bacterial virulence. This study demonstrates that mutator strains of Escherichia coli are selected in urinary tract infections, suggesting a role in pathogenesis.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Genetics

Background:

  • The mutator phenotype, associated with elevated mutation rates, is hypothesized to increase bacterial virulence.
  • Epidemiological data indicate a high prevalence of mutator strains in Escherichia coli urinary tract infection (UTI) isolates.
  • Experimental evidence directly linking the mutator phenotype to enhanced virulence has been limited.

Purpose of the Study:

  • To investigate whether the mutator phenotype confers a selective advantage during urinary tract infections.
  • To experimentally validate the association between increased mutation rates and virulence in Escherichia coli.

Main Methods:

  • Utilized the uropathogenic Escherichia coli strain CFT073 and its isogenic mutS- mutant (a mutator strain).
  • Assessed the in vitro selection of the mutator strain in urine.
  • Evaluated the in vivo selection of the mutator strain during the late stages of a mouse model of urinary tract infection.

Main Results:

  • The mutator strain demonstrated a selective advantage in vitro when cultured in urine.
  • In a mouse model of urinary tract infection, the mutator strain was also selected during the late stages of infection.
  • These findings provide experimental evidence supporting the role of the mutator phenotype in pathogenesis.

Conclusions:

  • The mutator phenotype can confer a selective advantage under specific conditions, such as urinary tract infections.
  • This study provides experimental evidence for the link between the mutator phenotype and enhanced pathogenesis in Escherichia coli.
  • The findings highlight the importance of genetic instability in bacterial virulence strategies.

Related Concept Videos

Microbiota of the Urogenital Tract01:28

Microbiota of the Urogenital Tract

The human urogenital system, once thought to be sterile in healthy individuals, is now recognized as a complex microbial habitat. Advancements in molecular sequencing techniques have revealed that even in healthy adults, the kidneys and bladder harbor microbial populations similar to those found in the distal urethra, albeit in much lower abundance. These resident microorganisms, while generally innocuous, can become opportunistic pathogens under conditions that alter the urogenital...
Transduction01:16

Transduction

Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome are...
Evolution of New Traits in Microbes01:24

Evolution of New Traits in Microbes

Microorganisms evolve rapidly due to their large population sizes and short generation times, often exhibiting measurable changes within days under laboratory conditions. Natural selection acts on standing genetic variation, enabling the retention and amplification of beneficial traits that confer fitness advantages in changing environments.Adaptive Pigment Regulation in RhodobacterIn Rhodobacter, a genus of purple non-sulfur bacteria, light-harvesting pigments such as bacteriochlorophyll and...
Urinary Tract Infection II: Pathophysiology01:25

Urinary Tract Infection II: Pathophysiology

The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
Mutations in Microorganisms01:18

Mutations in Microorganisms

Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...