Hfq Regulates Efflux Pump Expression and Purine Metabolic Pathway to Increase Trimethoprim Resistance in Aeromonas veronii.

Dan Wang,Xiang Ma,Hongqian Tang,Yanqiong Tang,Zhu Liu,Dongyi Huang,Min Lin,Hong Li

doi:10.3389/fmicb.2021.742114

Dan Wang, Xiang Ma + Show 6 more

Open Access

https://doi.org/10.3389/fmicb.2021.742114

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Abstract

Aeromonas veronii (A. veronii) is a zoonotic pathogen. It causes clinically a variety of diseases such as dysentery, bacteremia, and meningitis, and brings huge losses to aquaculture. A. veronii has been documented as a multiple antibiotic resistant bacterium. Hfq (host factor for RNA bacteriophage Qβ replication) participates in the regulations of the virulence, adhesion, and nitrogen fixation, effecting on the growth, metabolism synthesis and stress resistance in bacteria. The deletion of hfq gene in A. veronii showed more sensitivity to trimethoprim, accompanying by the upregulations of purine metabolic genes and downregulations of efflux pump genes by transcriptomic data analysis. Coherently, the complementation of efflux pump-related genes acrA and acrB recovered the trimethoprim resistance in Δhfq. Besides, the accumulations of adenosine and guanosine were increased in Δhfq in metabonomic data. The strain Δhfq conferred more sensitive to trimethoprim after appending 1 mM guanosine to M9 medium, while wild type was not altered. These results demonstrated that Hfq mediated trimethoprim resistance by elevating efflux pump expression and degrading adenosine, and guanosine metabolites. Collectively, Hfq is a potential target to tackle trimethoprim resistance in A. veronii infection.

Highlights

Aeromonas veronii (A. veronii) is a rod-shaped gram-negative pathogen found in diseased grass fish, tilapia, and turtles
The mutant hfq was more sensitive to trimethoprim than wild type, which exhibited with a minimum inhibitory concentration (MIC) of 8 μg/mL in contrast to 16 μg/mL of wild type
Previous studies revealed that Hfq acts on a variety of membrane-associated protein genes, affecting bacterial growth, cell membrane formation, virulence, drug resistance, stress tolerance, and retention of retained bacteria (Hayashi-Nishino et al, 2012; Zhang et al, 2019)

Summary

Introduction

Aeromonas veronii (A. veronii) is a rod-shaped gram-negative pathogen found in diseased grass fish, tilapia, and turtles. It can cause huge losses in the aquaculture industry and infect humans (Liu et al, 2015; Wang et al, 2019). Hfq is a relatively common molecular chaperone that interacts with small RNAs to mediate the binding of small RNA to mRNA and assists in the post-transcriptional regulation of bacterial genes. Hfq participates in several regulatory pathways as a global regulator (Kakoschke et al, 2016)

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