The Sub-inhibitory Effect of Azithromycin and Ciprofloxacin on virF Gene Expression in Enteroinvasive Escherichia coli and Shigella flexneri

Abstract
Background: Bacillary dysentery is an invasive bacterial gastroenteritis that damages the colon epithelium and leads to bloody diarrhea. Enteroinvasive Escherichia coli (EIEC) and Shigella flexneri are two major etiologic agents of the disease. The virF gene is a transcriptional regulator of the virulence genes involved in the invasion of these bacteria. Previous studies have shown that sub-minimum inhibitory concentrations (sub-MICs) of antibiotics have significant effects on bacterial virulence. Objectives: This study aimed to evaluate the effects of sub-MICs of ciprofloxacin and azithromycin on S. flexneri and EIEC. Methods: Prototype strains of both bacteria were treated with sub-MICs of 1/2, 1/4, and 1/8 of ciprofloxacin and azithromycin antibiotics. Changes in the expression of the virF gene in antibiotic-treated samples compared to control samples were analyzed using relative real-time polymerase chain reaction (PCR). Results: The mean expression of the virF gene in all sub-MICs of ciprofloxacin was increased in both S. flexneri and EIEC, while a down-regulation was observed in sub-MICs of azithromycin. These gene expression changes were dose-dependent. Conclusions: The results demonstrated that the virulence of S. flexneri and EIEC is affected by sub-MICs of azithromycin and ciprofloxacin. Given that azithromycin, unlike ciprofloxacin, reduces the severity of infection at sub-MICs, it is a more appropriate choice with a lower risk for treating acute infections caused by these bacteria.
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