Quorum sensing regulatory protein LsrR affects Avian Pathogenic Escherichia coli pathogenicity by regulating cysN
Description
Avian Pathogenic Escherichia coli (APEC) is a strain of extraintestinal pathogenic E. coli that is the primary cause of economic loss, has acquired antibiotic resistance, and poses a significant challenge to medical microbiologists in impoverished countries. In APEC, cysN is essential for cysteine synthesis, which is required for protein synthesis, along with the creation of numerous sulfur-containing compounds for bacterial growth and metabolism. However, the involvement of cysN in APEC pathogenicity has not been investigated. To investigate the function of cysN in APEC, cysN gene mutant and complemented strains were constructed and biologically characterized. The results determined that Quorum Sensor regulator LsrR directly binds to the cysN promoter to a region between -289 to -319 of the cysN promoter and inactivation of the cysN gene decreased biofilm formation (P < 0.01), serum resistance (P < 0.05), adhesion (P < 0.01), invasion capacity (P < 0.05) of APEC94 towards host cells, reduced transcription levels of fimbrial, flagellar, and virulence genes (P < 0.05), altered antibiotic resistance characteristic, and reducing APEC94 colonization in blood, lungs, liver, spleen, and intestine (P < 0.05) in mice, and the mortality rate of mutant APEC94∆cysN and APEC94 was 12.5% and 87.5% in a mice infection model respectively. In addition, the results revealed that cysN positively affects the expression of flagellar, type 1 fimbria, and virulence genes in APEC. However, the expression levels of virulence genes such as csgF, fyuA, yjaA, chuA, ompA, and iss were not influenced compared to the wild-type strain. Similarly, the transcription level of the inflammatory cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and INF-ƴ was significantly decreased in mutant APEC94ΔcysN strain infected tissues compared with the wild-type strain (P < 0.05). These results indicate that regulator cysN contributes to the virulence and pathogenicity of APEC.
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Iran National Science Foundation
U22A20518, 32072829, and 32302883