Gentamicin Combined With Hypoionic Shock Rapidly Eradicates Aquaculture Bacteria in vitro and in vivo

Abstract

Bacterial pathogens are a major cause of infectious diseases in aquatic animals. The abuse of antibiotics in the aquatic industry has led to the proliferation of antibiotic resistance. It is therefore essential to develop more effective and safer strategies to increase the efficacy and extend the life span of the antibiotics used in aquaculture. In this study, we show that six aquaculture bacterial pathogens (i.e., Aeromonas hydrophila, Vibrio alginolyticus, Edwardsiella tarda, Streptococcus iniae, Vibrio harveyi, and Vibrio fluvialis) in the stationary phase can be rapidly killed after immersion in gentamicin- or neomycin-containing, ion-free solutions for a few minutes. Such hypoionic shock treatment enhances the bacterial uptake of gentamicin in an ATP-dependent manner. Importantly, we demonstrate, as a proof of concept, that gentamicin under hypoionic shock conditions can effectively kill A. hydrophila in vivo in a skin infection model of zebrafish (Danio rerio), completely curing the infected fish. Given that pathogenic bacteria generally adhere to the skin surface and gills of aquatic animals, our strategy is of potential significance for bacterial infection control, especially for small-scale economic fish farming and ornamental fish farming. Further, the combined treatment can be completed within 5 min with a relatively small volume of solution, thus minimizing the amount of residual antibiotics in both animals and the environment.

Heat shock potentiates aminoglycosides against gram-negative bacteria by enhancing antibiotic uptake, protein aggregation, and ROS

“…The bacterial uptake of aminoglycosides is critical for aminoglycoside potentiation as elicited by metabolic recovery ( 13 , 18 , 46 , 47 ), rapid freezing ( 26 ), hypoionic shock ( 23 – 25 ), or chemical induction ( 34 , 35 , 48 ). Therefore, we examined whether heat shock could enhance the bacterial uptake of aminoglycosides using tobramycin extraction coupled with cell-growth inhibition assay, a recently explored method ( 26 ).…”

“…found that osmotic compounds could potentiate typical antibiotics against Acinetobacter baumannii biofilms ( 21 ). We previously observed that hypoionic shock (i.e., treatment with ion-free solutions) and rapid freezing dramatically potentiate aminoglycosides against bacterial persisters by activating mechanosensitive channels and enhancing antibiotic uptake ( 22 – 26 ). In addition, photothermal materials have been developed to potentiate various antibiotics by imposing chemical and physical effects ( 27 ).…”

Glutamine potentiates gentamicin to kill lab-evolved gentamicin-resistant and clinically isolated multidrug-resistant Escherichia coli

“…Conventional antibiotic treatments against bacterial infections are becoming ineffective due to the widespread antibiotic resistance worldwide, demanding the development of new antibiotics (Mühlberg et al, 2020;Vila et al, 2020). However, classical approaches that develop new antibiotics are not sufficient for the current pipeline, therefore new strategies are crucially needed to overcome antibiotic-resistant bacteria (Breijyeh et al, 2020;Gao et al, 2021;Ramanathan et al, 2021).…”