D-amino acid enhanced the sensitivity of avian pathogenic Escherichia coli to tetracycline and amikacin

Jing Wu ¹ Bin Yang ^1* Wei Jiang ² Huifang Yin ^2* Xiangan Han ^2* Lili Zhang ^3*

• ¹ Tarim University, Aral, China
• ² Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, Shanghai Municipality, China
• ³ College of Life Sciences, Longyan University, Longyan, Fujian Province, China

Avian pathogenic Escherichia coli (APEC) biofilm formation has led to increased antibiotic resistance, presenting a significant challenge for the prevention and control of the disease. While certain D-amino acids have been shown to inhibit the formation of various bacterial biofilms, their role in APEC remains unexplored. This study investigates the effects of 19 different D-amino acids (D-AAs) on clinically isolated APEC biofilm. The results showed that D-tyrosine, D-leucine, D-tryptophan and D-methionine can reduce APEC biofilm formation by over 50% at a concentration of 5 mM. Subsequently, four D-AAs were selected for combination treatment with antibiotics (ceftazidime, amikacin, tetracycline and ciprofloxacin). The findings reveal that D-tyrosine enhance the sensitivity of APEC to amikacin and tetracycline, while D-methionine increases the sensitivity of APEC to amikacin. The mechanisms by which D-tyrosine and D-methionine enhance antibiotic sensitivity were further investigated. Following treatment with D-tyrosine and D-methionine, scanning electron microscope (SEM) observations indicated a reduction in the numberof bacteria on the surface of the cell crawl, but the shape and structure of the cells remain unchanged. Notably, the surface hydrophobicity was decreased by 33.86% and 56%, and the output of extracellular polysaccharide was decreased by 46.63% and 57.69%, respectively. Additionally, genes related to biofilm synthesis (pgaA, pgaC and luxS) were down-regulated (p<0.05), whereas porin protein-encoding genes (ompC and ompF) were up-regulated (p<0.05). which inhibited formation of biofilm and enhanced the sensitivity of APEC to amikacin and tetracycline and by decreasing the hydrophobicity and extracellular polysaccharide content on cell surfaceand up-regulated porin genes and down-regulating the genes related to biofilm formation.According to the different D-AAs involved in this study, it can provide new ideas for the treatment of APEC.