Reversal of Azithromycin Resistance in Staphylococcus saprophyticus by Baicalin.

Jinli Wang,Kun Li,Jinxue Ding,Jinwu Meng,Tianxin Qiu,Wenjia Wang,Yi Wu,Zhenguang Liu,Jiaguo Liu,Deyun Wang,Jinyue Zhu

doi:10.3389/fvets.2022.827674

Jinli Wang, Kun Li + Show 9 more

Open Access

https://doi.org/10.3389/fvets.2022.827674

Copy DOI

Abstract

In recent years, the efficacy of antibiotics has been threatened by the evolution of bacterial resistance. We previously demonstrated that baicalin (Bac) showed synergies with azithromycin (Azm) against Azm-resistant Staphylococcus saprophyticus (ARSS). The aim of this study was to explore the roles of Bac in reversing the resistance of ARSS to Azm. The ARSS was sequentially passaged for 20 days with the sub-MIC (minimum inhibitory concentration) of Bac. The strain that recovered sensitivity to Azm was named Azm-sensitive S. saprophyticus (ASSS). The sub-MIC of Bac reversed the resistance of ARSS to Azm. The MIC of Azm against the ASSS strain was 0.488 mg/l, and it was stable within 20 passages. The highest rate of resistance reversal reached 3.09% after ARSS was exposed to 31.25 mg/l Bac for 20 days. Furthermore, semiquantitative biofilm and RT-PCR assays reflected that the ability of biofilm formation and the transcript levels of msrA, mphC, and virulence-associated genes in the ASSS strain were significantly lower than those of the ARSS strain (p < 0.05). Simultaneously, Azm delayed the start time of death, alleviated the injury of the kidney, and decreased the bacterial burden in organs and cytokine levels in mice infected with ASSS. In contrast, Azm did not have a good therapeutic effect on mice infected with ARSS. Therefore, Bac has the potential to be an agent that reversed the resistance of ARSS to Azm.

Highlights

Staphylococcus saprophyticus (S. saprophyticus), coagulase-negative coccus, causes urinary tract infections [1], francolin ophthalmia [2], and bovine mastitis [3]
Azm-resistant S. saprophyticus (Azm MIC of 1,000 mg/l determined by the broth micro-dilution method) was isolated from francolins suffering from ophthalmia in a francolin farm located in Jiangsu province, China [2]
The reason for the phenomenon is that 62.5–250 mg/l Bac moderately inhibited the growth of Azm-resistant S. saprophyticus (ARSS) (Figure 1)

Summary

Introduction

Staphylococcus saprophyticus (S. saprophyticus), coagulase-negative coccus, causes urinary tract infections [1], francolin ophthalmia [2], and bovine mastitis [3]. Macrolide antibiotics have often been used to treat infections induced with staphylococcus and streptococcus [4]. The presence of resistance in food could be a severe threat to public health due to the possible spread of antibiotic resistance [7]. Resistance rates continue to rise, and the rate of antibiotic discovery has decreased substantially. Drug-resistant bacteria remain a severe threat to the efficacy of antibiotics. The methods of preventing the spread of antibiotic resistance need to be prioritized [10, 11]

Objectives

Methods

Results

Conclusion