Transcriptomic and proteomic analysis of the virulence inducing effect of ciprofloxacin on enterohemorrhagic Escherichia coli

PLoS One. 2024 May 24;19(5):e0298746. doi: 10.1371/journal.pone.0298746. eCollection 2024.

Abstract

Enterohemorrhagic E. coli (EHEC) is considered to be the most dangerous pathotype of E. coli, as it causes severe conditions such as hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). Antibiotic treatment of EHEC infections is generally not recommended since it may promote the production of the Shiga toxin (Stx) and lead to worsened symptoms. This study explores how exposure to the fluoroquinolone ciprofloxacin reorganizes the transcriptome and proteome of EHEC O157:H7 strain EDL933, with special emphasis on virulence-associated factors. As expected, exposure to ciprofloxacin caused an extensive upregulation of SOS-response- and Stx-phage proteins, including Stx. A range of other virulence-associated factors were also upregulated, including many genes encoded by the LEE-pathogenicity island, the enterohemolysin gene (ehxA), as well as several genes and proteins involved in LPS production. However, a large proportion of the genes and proteins (17 and 8%, respectively) whose expression was upregulated upon ciprofloxacin exposure (17 and 8%, respectively) are not functionally assigned. This indicates a knowledge gap in our understanding of mechanisms involved in EHECs response to antibiotic-induced stress. Altogether, the results contribute to better understanding of how exposure to ciprofloxacin influences the virulome of EHEC and generates a knowledge base for further studies on how EHEC responds to antibiotic-induced stress. A deeper understanding on how EHEC responds to antibiotics will facilitate development of novel and safer treatments for EHEC infections.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Ciprofloxacin* / pharmacology
  • Enterohemorrhagic Escherichia coli / drug effects
  • Enterohemorrhagic Escherichia coli / genetics
  • Enterohemorrhagic Escherichia coli / pathogenicity
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial / drug effects
  • Humans
  • Proteome / metabolism
  • Proteomics* / methods
  • Transcriptome* / drug effects
  • Virulence / drug effects
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Ciprofloxacin
  • Escherichia coli Proteins
  • Anti-Bacterial Agents
  • Virulence Factors
  • Proteome

Grants and funding

The authors received no specific funding for this work.