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Mechanistic understanding of antibiotic resistance mediated by EnvZ/OmpR two-component system in Salmonella enterica

Duhyun Ko1,2, Sang Ho Choi1,2,3

  • 1National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.

The Journal of Antimicrobial Chemotherapy
|July 5, 2022
PubMed
Abstract

Insights

The EnvZ/OmpR system in Salmonella Enteritidis remodels outer membrane porins (OMPs) to enhance resistance against beta-lactam antibiotics. This mechanism helps the bacteria survive antibiotic exposure.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Outer membrane porins (OMPs) are crucial for antibiotic entry into bacteria.
  • Modulation of OMPs is linked to multidrug resistance in Salmonella Enteritidis.

Purpose of the Study:

  • To elucidate the mechanism of EnvZ/OmpR two-component system-mediated antibiotic resistance in S. Enteritidis.
  • To understand how EnvZ/OmpR regulates OMP expression in response to antibiotics.

Main Methods:

  • Utilized specific S. Enteritidis strains (envZP248L, envZH243A) mimicking active/inactive EnvZ/OmpR states.
  • Assessed antibiotic resistance via broth microdilution and spot plating.
  • Analyzed transcriptomes using RNA-seq, complemented by Western blot, qRT-PCR, EMSA, and β-galactosidase assays.

Main Results:

  • Active EnvZ/OmpR modulated expression of OMP genes (SEN1522, SEN2875, ompD, ompW), increasing resistance to beta-lactams.
  • OmpR directly activated SEN1522/SEN2875 and repressed ompD/ompW.
  • EnvZ/OmpR upregulated its own expression under beta-lactam stress, reducing outer membrane permeability.

Conclusions:

  • EnvZ/OmpR plays a key role in remodeling OMP composition.
  • This remodeling enhances S. Enteritidis survival against beta-lactam antibiotics.

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