Journal of Integrative Agriculture (Feb 2023)
The vital role of covS in the establishment of Streptococcus equi subsp. zooepidemicus virulence
Abstract
Streptococcus equi subsp. zooepidemicus (SEZ) is an important zoonotic agent. Here, a virulence-attenuated strain M35246 derived from natural variation of wild-type SEZ ATCC35246 was found. M35246 showed a deletion of 25 contiguous genes as well as a loss-of-function mutation in covS. Subsequently, a 25-gene-deleted strain (ΔPI), a covS-mutant strain (McovS), and relevant complementary strains were constructed and investigated. M35246 and McovS were significantly less encapsulated and exhibited poorer anti-phagocytic capacity compared to wild-type SEZ. McovS was significantly more sensitive to β-lactams, aminoglycosides, macrolides, and lincosamides than wild-type SEZ. M35246, McovS, and ΔPI exhibited an increase in median lethal dose (LD50) in mice by 105, 105, and 5 times when compared to wild-type SEZ, respectively. Neither M35246 nor McovS were isolated from mice 48 h after being challenged with approximately 2 000 times the LD50 of wild-type SEZ. Transcriptome analysis showed that 668 significantly differentially expressed genes existed between McovS and wild-type SEZ. Numerous virulence factor-encoding genes and anabolic-related genes in McovS that were involved in anti-phagocytosis, capsule formation, pathogenicity, and antibiotic resistance were downregulated significantly relative to the wild-type strain. This study revealed that the CovS plays a vital role in the establishment of SEZ virulence.