Ethyl-N-dodecanoyl-l-arginate hydrochloride combats pathogens with low-resistance generation by membrane attack and modifies gut microbiota structure.

Ting Shao,Zhenliang Sun,Wenshu Tang,Huang Chen,Tingting Fan,Yanting Sun,Zhengfang Yi,Song Gao,Mingyao Liu

doi:10.1111/1751-7915.13514

Abstract

SummaryEthyl‐N‐dodecanoyl‐l‐arginate hydrochloride (LAE, ethyl lauroyl arginate HCl) is a cationic surfactant used as a food preservative with broad‐spectrum antibacterial activities. However, its resistance development, influences on gut microbiome and molecular target are unclear. In this study, bacteria were stimulated by LAE for 30 days to test the bacterial resistance. Several infected animal models were used to evaluate the antibacterial effect of LAE in vivo. Mice were orally treated with LAE to test its effect on animal growth. The influence of LAE on mice gut microbiome was analysed by 16S rDNA sequencing. The results indicated that Escherichia coli did not develop resistance to LAE. LAE significantly combats bacterial infection in mice, ducklings and piglets. Moreover, LAE promotes mouse weight gain without changing body composition or reducing animal vitality, and induces lower hepatotoxicity than ampicillin. In the mouse gut microbiome assessment and characterization, LAE modifies host gut microbiota structure. Mechanistically, LAE specifically binds to acidic phospholipids including phosphatidylserine, depolarizes the membrane and disrupts the bacterial membrane followed by bacterial growth inhibition. This study investigates the molecular mechanism of LAE as well as its antibacterial functions in poultry and livestock. Our data suggest LAE is a potential antibacterial agent in animal health.

Highlights

Resistance development limits the useful lifespan of antibacterial agents, and the consequent failure of antibiotic therapy has restored infectious diseases to the list of leading causes of death worldwide, causing a public health crisis (2018)
Antibiotics fight against bacterial infection, and they are used as growth promoters in animals to increase weight gain partly by attenuation of the intestine wall (Hendrickx, et al, 2015), such as ampicillin (AMP), a b-lactam antibiotic with a broad spectrum (Butaye, et al, 2003; Cho, et al, 2012; Danzeisen, et al, 2015; Redondo, et al, 2015)
We evaluated the antibacterial efficacy of LAE by determining its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Staphylococcus aureus and E. coli

Summary

Introduction

Resistance development limits the useful lifespan of antibacterial agents, and the consequent failure of antibiotic therapy has restored infectious diseases to the list of leading causes of death worldwide, causing a public health crisis (2018). As membrane targeting antibacterial molecules destroy the first line of bacteria defence, they render bacteria less likely to develop resistance (Wenzel, et al, 2014; Lam et al, 2016). In addition to inducing antibiotic-resistant bacteria (Levy and Marshall, 2004; Gullberg, et al, 2011; Wang, et al, 2017; Zurfluh, et al, 2017), antibiotics disturb the gut microbiome because they are unfavourable to the growth of probiotic bacteria and promote the expansion of pathogens (Pallav, et al, 2014; de Gunzburg, et al, 2018). Bifidobacterium and Lactobacillus are the most widely studied probiotic bacteria in the human or animal gut possessing distinct beneficial attributes by strengthening the intestinal barrier, modulating the immune response and antagonizing pathogens either by the production of antimicrobial compounds or through competition for mucosal binding sites (Gao, et al, 2017). Its molecular target, effects on drug resistance development and influence on antibacterial activity and the gut microbiome in vivo are not clarified.

Results

Discussion

Experimental procedures