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The protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila CW strain was explored by observing the clinical signs and histopathology, measuring the cumulative mortality, serum biochemical and non-specific immune indicators, and intestinal microbiota in this study. The cumulative survival rate of the cinnamaldehyde within 14 days was significantly higher than that of the challenge group, which was 70% and 20%, respectively. Compared with the challenge group, the activities of lysozyme, superoxide dismutase, and glutathione peroxidase in the treatment group were increased, while there was no significant difference in catalase activity. Compared with the challenge group, the histopathology results showed that the injury of liver, spleen, and kidney was significantly alleviated after cinnamaldehyde treatment. The results of intestinal microbiota showed that the proportion of Proteobacteria in the challenge group was significantly increased, and the proportion of Aeromonas sp. reached 30% based on the analysis of species classification level. The composition of dominant species in the treatment group was similar to the control group. In conclusion, cinnamaldehyde increased the cumulative survival rate of channel catfish infected by A. hydrophila. It could protect channel catfish through improving the non-specific immune function of channel catfish, alleviating the pathological lesions of liver, spleen, kidney, and intestine, and maintaining the relative balance of the intestinal microbiota. Therefore, cinnamaldehyde could be a candidate drug for the treatment of A. hydrophila infection. • Cinnamaldehyde improved the nonspecific immunity of channel catfish and alleviated the lesions caused by A. hydrophila. • Cinnamaldehyde can maintain the relative balance of intestinal microbiota and inhibit the Proteobacteria. • Laying the foundation for the application of cinnamaldehyde in aquaculture to resist drug-resistant A. hydrophila infection. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila , a highly infectious pathogen, causes several infections in aquatic animals and huge economic losses. Antibiotics are often used to treat A. hydrophila infections. However, overuse and irrational usage of antibiotics has led to severe antibiotic residues and emergence of resistance. There is therefore an urgent need for a new sustainable drug to control bacterial infection. Cinnamaldehyde, a plant-derived ingredient, has been found to have good antibacterial activity against A. hydrophila in vitro , but its mechanism of action remains unknown. In this study, we investigated the mechanism of cinnamaldehyde against A. hydrophila by evaluating the effects of cinnamaldehyde on A. hydrophila cell growth, cell morphology, electrical conductivity, lactate dehydrogenase (LDH), protein metabolism and DNA. The minimal inhibitory concentration and minimum bactericidal concentration of cinnamaldehyde were 256 and 512 μg/mL, respectively. Microscopy results showed disrupted cell wall and membrane, loss of cytoplasm, interior cavitation and unusual binary fission in the cinnamaldehyde-treated group. Electrical conductivity, LDH activity content and DNA extravasation in cinnamaldehyde-treated A. hydrophila increased by 7.14%, 16.75% and 20.29 μg/mL, respectively. Furthermore, nucleic acid fluorescence intensity and density decreased over time in the cinnamaldehyde-treated group. Taken together, these findings suggest that cinnamaldehyde can inhibit the growth of A. hydrophila by disrupting cell membranes and affecting protein metabolism. • Cinnamaldehyde can inhibit the growth of drug-resistant A. hydrophila by disrupting the cell morphology. • Cinnamaldehyde may affect protein metabolism by inhibiting DNA synthesis in drug-resistant A. hydrophila. • Laying the foundation for the development of a new drug for the treatment of drug-resistant A. hydrophila infection. [ABSTRACT FROM AUTHOR]