Deletion of lacD gene affected stress tolerance and virulence of Streptococcus suis serotype 2.

Abstract

Streptococcus suis type 2 (S. suis type 2, SS2), an infectious pathogen which is zoonotic and can induce severely public health concern. Our previous research identified a newly differential secreted effector of tagatose-bisphosphate aldolase (LacD) mediated by VirD4 factor within the putative type IV secretion system of SS2, whereas the functional basis and roles in virulence of LacD remain elusive. Here in this study, the LacD was found enzymatic and can be activated to express under oxidative stress. Gene mutant and its complemental strain (ΔlacD and cΔlacD) were constructed to analyze the phenotypes, virulence and transcriptomic profiles as compared with the parental strain. The lacD gene deletion showed no effect on growth capability and cells morphology of SS2. However, reduced tolerance to oxidative and heat stress conditions, increased antimicrobial susceptibility to ciprofloxacin and kanamycin were found in ΔlacD strain. Further, the LacD deficiency led to weakened invasion and attenuated virulence since an easier phagocytosed and more prone to be cleared of SS2 in macrophages were shown in ΔlacD mutant. Distinctive transcriptional profiling in ΔlacD strain and typical down-regulated genes with significant mRNA changes including alcohol dehydrogenase, GTPase, integrative and conjugative elements, and iron ABC transporters which were mainly involved in cell division, stress response, antimicrobial susceptibility and virulence regulation, were examined and confirmed by RNA sequencing and real time qPCR. In summary, the results demonstrated for the first time that LacD was a pluripotent protein mediated the metabolic, stress and virulent effect of SS2.