Increased Levels of (p)ppGpp Correlate with Virulence and Biofilm Formation, but Not with Growth, in Strains of Uropathogenic Escherichia coli

Int J Mol Sci. 2023 Feb 7;24(4):3315. doi: 10.3390/ijms24043315.

Abstract

Urinary tract infections are one of the most frequent bacterial diseases worldwide. UPECs are the most prominent group of bacterial strains among pathogens responsible for prompting such infections. As a group, these extra-intestinal infection-causing bacteria have developed specific features that allow them to sustain and develop in their inhabited niche of the urinary tract. In this study, we examined 118 UPEC isolates to determine their genetic background and antibiotic resistance. Moreover, we investigated correlations of these characteristics with the ability to form biofilm and to induce a general stress response. We showed that this strain collection expressed unique UPEC attributes, with the highest representation of FimH, SitA, Aer, and Sfa factors (100%, 92.5%, 75%, and 70%, respectively). According to CRA (Congo red agar) analysis, the strains particularly predisposed to biofilm formation represented 32.5% of the isolates. Those biofilm forming strains presented a significant ability to accumulate multi-resistance traits. Most notably, these strains presented a puzzling metabolic phenotype-they showed elevated basal levels of (p)ppGpp in the planktonic phase and simultaneously exhibited a shorter generation time when compared to non-biofilm-forming strains. Moreover, our virulence analysis showed these phenotypes to be crucial for the development of severe infections in the Galleria mellonella model.

Keywords: E. coli; Galleria mellonella; UPEC; UTI; antibiotic resistance; biofilm; infection; pathogenicity; phenotype; ppGpp; stringent response; virulence.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Escherichia coli Infections* / microbiology
  • Guanosine Pentaphosphate
  • Humans
  • Urinary Tract Infections* / microbiology
  • Uropathogenic Escherichia coli* / genetics
  • Virulence / genetics
  • Virulence Factors / genetics

Substances

  • Anti-Bacterial Agents
  • Guanosine Pentaphosphate
  • Virulence Factors