Luteolin increases susceptibility to macrolides by inhibiting MsrA efflux pump\xa0in Trueperella pyogenes

Yuru Guo,Mingchun Liu,Menghan Chen,Luyao Zhang,Zehui Zhang,Chengcheng Huang,Dexian Zhang,Hongyu Su,Ruxia Wang

doi:10.1186/s13567-021-01021-w

Yuru Guo, Mingchun Liu + Show 7 more

Open Access

https://doi.org/10.1186/s13567-021-01021-w

Copy DOI

Journal: Veterinary Research	Publication Date: Jan 10, 2022
Citations: 8	License type: open-access

Affiliation: Shenyang Agricultural University

Abstract

Trueperella pyogenes (T. pyogenes) is an opportunistic pathogen associated with a variety of diseases in many domestic animals. Therapeutic treatment options for T. pyogenes infections are becoming limited due to antimicrobial resistance, in which efflux pumps play an important role. This study aims to evaluate the inhibitory activity of luteolin, a natural flavonoid, on the MsrA efflux pump and investigate its mechanism. The results of antimicrobial susceptibility testing indicated that the susceptibility of msrA-positive T. pyogenes isolates to six macrolides increased after luteolin treatment, while the susceptibility of msrA-negative isolates showed no change after luteolin treatment. It is suspected that luteolin may increase the susceptibility of T. pyogenes isolates by inhibiting MsrA activity. After 1/2 MIC luteolin treatment for 36 h, the transcription level of the msrA gene and the expression level of the MsrA protein decreased by 55.0–97.7% and 36.5–71.5%, respectively. The results of an affinity test showed that the equilibrium dissociation constant (KD) of luteolin and MsrA was 6.462 × 10–5 M, and hydrogen bonding was predominant in the interaction of luteolin and MsrA. Luteolin may inhibit the ATPase activity of the MsrA protein, resulting in its lack of an energy source. The current study illustrates the effect of luteolin on MsrA in T. pyogenes isolates and provides insight into the development of luteolin as an innovative agent in combating infections caused by antimicrobial-resistant bacteria.

Highlights

Trueperella pyogenes (T. pyogenes), formerly classified as Corynebacterium pyogenes, is a gram-positive, non-spore-forming, nonencapsulated, nonmotile, pleomorphic, rod-shaped bacterium [1,2,3]
The Minimum inhibitory concentrations (MICs) of luteolin against each isolate were the MICs of six macrolides against msrA-negative T. pyogenes isolates (HC-H10 and RY14-3) showed no changes, which indicated that luteolin may influence the MsrA efflux pump activity in T. pyogenes, leading to a decrease in macrolide resistance
It was found that 1/2 MIC luteolin treatment for 36 h could best increase the susceptibility of T. pyogenes to macrolides

Summary

Introduction

Trueperella pyogenes (T. pyogenes), formerly classified as Corynebacterium pyogenes, is a gram-positive, non-spore-forming, nonencapsulated, nonmotile, pleomorphic, rod-shaped bacterium [1,2,3]. T. pyogenes is an opportunistic and zoonotic pathogen. In domestic and wildlife animals, it often causes various suppurative infections, including liver abscess, arthritis, pneumonia, metritis, and mastitis [4, 5]. Trueperella pyogenes is an important causative agent in cattle and pigs due to the fact that it causes substantial economic losses [1]. The treatment of infections caused by T. pyogenes in veterinary clinics still relies on antibiotics [7,8,9]. The antimicrobial resistance of T. pyogenes is becoming severe because of the overuse of antimicrobial drugs in veterinary clinical treatment.

Objectives

Methods

Results

Conclusion