The two-component sensor factor envZ influences antibiotic resistance and virulence in the evolutionary dynamics of...

Area of Science:

• Microbiology
• Genetics
• Infectious Diseases

Background:

• Multidrug-resistant (MDR) Salmonella enteritidis poses a significant threat to public health.
• Understanding the genetic mechanisms underlying MDR and virulence is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of the two-component sensor envZ gene mutations in the antibiotic resistance and virulence of MDR Salmonella enteritidis.
• To explore the impact of envZ mutations on the evolutionary dynamics of clinical Salmonella enteritidis strains.

Main Methods:

• Whole genome sequencing (WGS) was used to analyze antibiotic resistance genes, virulence genes, and single nucleotide polymorphisms (SNPs).
• RNA sequencing and quantitative RT-PCR were employed to assess gene expression levels.
• Virulence was evaluated using a Galleria mellonella infection model and in vitro cell-based assays.

Main Results:

• envZ mutations were identified in clinical Salmonella enteritidis strains associated with invasive infections.
• These mutations led to reduced expression of outer membrane proteins ompD and ompF.
• envZ mutants exhibited enhanced virulence, increased adhesion, invasion, and resistance to phagocytosis, alongside reduced biofilm formation and growth rates.

Conclusions:

• The study identifies novel genetic roles for envZ in influencing antibiotic resistance and virulence in clinical Salmonella enteritidis.
• envZ mutations contribute to antibiotic resistance by down-regulating ompD and ompF expression and enhance bacterial virulence, promoting multisite infections with increased fitness.