Abstract
The overuse of antibiotics results in the development of antibiotic resistance and limits the useful life of these drugs in fighting bacteria, including Aeromonas hydrophila, a well-known opportunistic pathogen that causes serious infections in fish and other animals. In this study, we investigated the adaptive resistance mechanism in A. hydrophila by multiple proteomic methods. Dimethyl labeling and label-free methods were performed to compare the differential expression of proteins in response to various doses of oxytetracycline (OXY). The results point to the conclusions that, in response to OXY stress, translational processes increase the abundance of these proteins whereas largely central metabolic pathways decrease their abundance. To confirm our hypothesis, various exogenous metabolites were compounded with OXY, and the resulting survival capabilities were measured. Results show that 7 metabolites (malic acid, serine, methionine, etc.) significantly decreased the survival capabilities of A. hydrophila in the presence of OXY, whereas 4 metabolites (arginine, lysine, tyrosine, etc.) did the opposite. Further investigation suggests that a compound comprising exogenous metabolites in combination with various antibiotics could have a significant bactericidal effect and might come into widespread use, especially together with tetracycline antibiotics. These findings may provide new clues to the antimicrobial treatment of A. hydrophila infection.
Highlights
It is well known that owing to the abuse or misuse of antibiotics over the past 90 years, antibiotic resistance has become a serious healthcare problem
To investigate the adaptive resistance mechanism in A. hydrophila, two independent group samples were digested in solution to peptides and either labeled by chemical dimethyl labeling or directly submitted to high-resolution mass spectrometry (MS) for label-free quantification as biological replicates (Supplementary Table Dataset 1)
Our results showed that all the relative standard deviations of the protein, unique peptide, and peptide groups were lower than 5%, indicating that both methods have excellent repeatability
Summary
It is well known that owing to the abuse or misuse of antibiotics over the past 90 years, antibiotic resistance has become a serious healthcare problem. It has been reported that the prevalence of antibiotic-resistant strains of Aeromonas hydrophila, a typical fish pathogen that causes infectious disease outbreaks on farms, is increasing, resulting in huge economic losses[2]. Our previous research demonstrated that global regulatory pathways such as glycolysis/gluconeogenesis, pyruvate metabolism, and the tricarboxylic acid (TCA) cycle may play important roles in adaptive resistance[11,12,13]. We sought to investigate the bacterial adaptive resistance mechanism first by studying the differential expression of A. hydrophila under antibiotic oxytetracycline (OXY) stress (OXY being a drug that has been widely used in agriculture). Except for some well-known antibiotic-related proteins, our bioinformatic analysis represents the down-regulation of central metabolic pathways involved in the adaptive resistance mechanism. Our study showed that the antibiotic resistance of A. hydrophila could potentially be eliminated via applied proteomics and exogenous metabolite assays
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