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. 2024 Jun 6;13(11):1787.
doi: 10.3390/foods13111787.

Environmentally Relevant Concentrations of Tetracycline Promote Horizontal Transfer of Antimicrobial Resistance Genes via Plasmid-Mediated Conjugation

Haibo Zhou  1   2 , Zhaoxin Lu  1 , Xinmei Liu  2 , Xiaomei Bie  1 , Feng Xue  3 , Sijie Tang  2 , Qiushi Feng  2 , Yiyu Cheng  2 , Jun Yang  2
Affiliations

Environmentally Relevant Concentrations of Tetracycline Promote Horizontal Transfer of Antimicrobial Resistance Genes via Plasmid-Mediated Conjugation

Haibo Zhou et al. Foods. .

Abstract

The ubiquitous presence of antimicrobial-resistant organisms and antimicrobial resistance genes (ARGs) constitutes a major threat to global public safety. Tetracycline (TET) is a common antimicrobial agent that inhibits bacterial growth and is frequently detected in aquatic environments. Although TET may display coselection for resistance, limited knowledge is available on whether and how it might influence plasmid-mediated conjugation. Subinhibitory concentrations (3.9-250 ng/mL) of TET promoted horizontal gene transfer (HGT) via the mobilizable plasmid pVP52-1 from the donor Vibrio parahaemolyticus NJIFDCVp52 to the recipient Escherichia coli EC600 by 1.47- to 3.19-fold. The transcription levels of tetracycline resistance genes [tetA, tetR(A)], conjugation-related genes (traA, traD), outer membrane protein genes (ompA, ompK, ompV), reactive oxygen species (ROS)-related genes (oxyR, rpoS), autoinducer-2 (AI-2) synthesis gene (luxS), and SOS-related genes (lexA, recA) in the donor and recipient were significantly increased. Furthermore, the overproduced intracellular ROS generation and increased cell membrane permeability under TET exposure stimulated the conjugative transfer of ARGs. Overall, this study provides important insights into the contributions of TET to the spread of antimicrobial resistance.

Keywords: antimicrobial resistance genes; cell membrane permeability; conjugative transfer; reactive oxygen species; tetracycline.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Tetracycline dose-dependent growth inhibition curves of V. parahaemolyticus NJIFDCVp52 and E. coli EC600.
Figure 2
Figure 2
Conjugative transfer of the pVP52-1 plasmid from V. parahaemolyticus NJIFDCVp52 to E. coli EC600 induced by different concentrations of tetracycline. (A) Schematic of the conjugation assay; (B) effects of tetracycline on the conjugative transfer of the plasmid pVP52-1. Asterisks indicate significant difference (** p < 0.01, **** p < 0.0001).
Figure 3
Figure 3
Effects of tetracycline on ROS generation and membrane permeability in the donor (V. parahaemolyticus NJIFDCVp52) and recipient (E. coli EC600) strains. (A) Fold changes in ROS production; (B) fold changes in the fluorescence intensity of NPN; (C) fold changes in the fluorescence intensity of PI. Asterisks indicate significant difference (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).
Figure 4
Figure 4
Effect of tetracycline on the mRNA expression levels of NJIFDCVp52-related genes. (A) Fold changes in the expression of genes related to outer membrane proteins in the presence of different concentrations of TET relative to those in the presence of a drug-free solvent; (B) fold changes in the expression of genes related to ROS production, the SOS response and conjugation; (C) fold changes in the expression of genes related to tetracycline resistance. Asterisks indicate significant difference (* p < 0.05, ** p < 0.01, **** p < 0.0001).
Figure 5
Figure 5
Effect of tetracycline on the mRNA expression levels of EC600-related genes. Asterisks indicate significant difference (** p < 0.01, **** p < 0.0001).
Figure 6
Figure 6
Schematic of the underlying mechanisms by which tetracycline promoted the conjugative transfer of plasmid-borne ARGs. Tetracycline can promote conjugation via (1) induced overproduction of ROS, (2) stimulated the SOS response, (3) increased cell membrane permeability, and (4) stimulated expression of conjugation-related genes. Red arrows indicate upregulated expression.
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