Role of fdhD in the pathogenicity and its regulatory characteristics in avian pathogenic Escherichia coli
Description
Avian Pathogenic Escherichia coli (APEC) produces major economic losses in the poultry industry and may endanger human health. The pathogenic mechanisms of APEC are still not fully understood. The fdhD gene in E. coli is essential for the function of formate dehydrogenases (FDHs), which are key enzymes in various biological processes in bacteria, but little is known about the fdhD in APEC pathogenicity. In this study, the LsrR quorum-sensing regulator expresses the gene fdhD and binds to the region between -96 to -66 of the fdhD promoter. The two motifs 6 bp and 9 bp of the fdhD promoter are crucial for the LsrR binding. The results showed that the inactivation of fdhD in APEC94 (a strain was isolated from diseased poultry) did not affect the growth and motility of APEC94 but led to decreased biofilm formation (P < 0.01), and reduced serum resistance (P < 0.05), alters antibiotic susceptibility. Similarly, the deletion of fdhD declined the adhesion (P < 0.05) and invasion (P < 0.01) of APEC94 towards host cells, reducing APEC94 colonization in blood, lungs, liver, spleen, and intestine (P < 0.05) in mice, and the mortality rate of mutant APEC94∆fdhD and APEC94 was 12.5% and 87.5% in a mice infection model respectively. Furthermore, the fdhD positively affects the expression of fimbrial, flagellar, and virulence genes in APEC. Moreover, the transcription level of the inflammatory cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and INF-ƴ (P < 0.05) was significantly decreased in mutant APEC94ΔfdhD compared with the wild-type strain. Thus, fdhD is a global regulator that activates the transcription of several genes. The present results suggest that fdhD plays an important role in pathogenicity, making it a good target for managing infection with APEC
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National Natural Science Foundation of China
U22A20518, 32072829, and 32302883