Stk and Stp1 participate in Streptococcus suis serotype 2 pathogenesis by regulating capsule thickness and translocation of certain virulence factors

Liu, Hanze; Ye, Chaofeng; Fu, Hao; Yue, Min; Li, Xiaoliang; Fang, Weihuan

doi:10.1016/j.micpath.2020.104607

Cited by 8 publications

(6 citation statements)

References 38 publications

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“…Streptococcus suis only harbors one copy of the gene encoding STK. Several studies have revealed that ssSTK plays an important role in the growth, metabolism, and pathogenesis of S. suis (Zhu et al, 2014;Zhang et al, 2017;Hu et al, 2021;Liu et al, 2021). More importantly, our previous study has demonstrated that disruption of stk almost completely abolished the growth of S. suis in the minimal medium (Hu et al, 2021).…”

Section: Introductionmentioning

confidence: 91%

Inhibitors targeting the autophosphorylation of serine/threonine kinase of Streptococcus suis show potent antimicrobial activity

et al. 2022

Front. Microbiol.

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Antimicrobial resistance (AMR) is a global concern threatening public health. Developing novel antibiotics is one of the effective strategies to tackle AMR. Serine/threonine kinases (STKs) have been recently shown to play critical roles in the physiology and pathogenesis of several important bacterial pathogens which are regarded as a promising antimicrobial drug target. We previously reported the roles of STK in the regulation of bacterial cell division, metabolism, and pathogenesis in Streptococcus suis, an important zoonotic bacterial pathogen. In this study, we firstly identified the Thr167 and Ser175 residues in the activation loop of S. suis STK (ssSTK) as the kinase autophosphorylation sites. Phenotyping results demonstrated that the autophosphorylation deficient strain resembled the stk deletion strain showing essentiality for bacterial growth in minimal medium, abnormal morphology, and decreased virulence when compared with the wild-type S. suis SC19 strain. Based on these findings, we established an ssSTK inhibitor screening approach by measuring the growth of S. suis in a minimal medium and testing the autophosphorylation inhibition by measuring the consumption of ATP in an enzymatic reaction by ssSTK. A series of inhibitors against ssSTK are identified from a commercial kinase inhibitors library, including Staurosporine, K252a, AT9283, and APY29. These inhibitors showed antimicrobial activity in vitro. Moreover, by using Galleria mellonella larvae infection assay, compound APY29 displayed in vivo efficacy against S. suis infection. Additionally, it was predicted by molecular docking that these inhibitors could interact with ssSTK. Collectively, our data illustrated the essential roles of ssSTK autophosphorylation in the physiology and pathogenicity of S. suis and consider these inhibitors as promising antimicrobial lead compounds.

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Section: Introductionmentioning

confidence: 91%

Inhibitors targeting the autophosphorylation of serine/threonine kinase of Streptococcus suis show potent antimicrobial activity

et al. 2022

Front. Microbiol.

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“…Other examples are A. baumannii BfmRS involved in production of capsular EPS upon bacterial exposure to low concentrations of antibiotics (Geisinger and Isberg 2015 ) and ExPEC TCS Rcs, which controls EPS colanic acid production (Miajlovic and Smith 2014 ). Similar to TCS, eukaryotic-like serine/threonine kinase and phosphatase Stk and Stp1 of S. suis regulate capsule thickness and virulence factors, promoting virulence (Liu et al 2021 ). In S. pyogenes , CovRS regulates virulence factors involved in complement resistance in a strain-dependent manner (Sugareva et al 2010 ).…”

Section: Bacterial Factors Mediating Adaptive Response To Bloodmentioning

confidence: 99%

Determinants of bacterial survival and proliferation in blood

Lê-Bury,

Echenique-Rivera,

Pizarro-Cerdá

et al. 2024

FEMS Microbiology Reviews

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Bloodstream infection is a major public health concern associated with high mortality and high healthcare costs worldwide. Bacteremia can trigger fatal sepsis whose prevention, diagnosis and management have been recognized as a global health priority by the World Health Organization. Additionally, infection control is increasingly threatened by antimicrobial resistance, which is the focus of global action plans in the framework of a One Health response. In-depth knowledge of the infection process is needed to develop efficient preventive and therapeutic measures. The pathogenesis of bloodstream infection is a dynamic process resulting from the invasion of the vascular system by bacteria, which finely regulate their metabolic pathways and virulence factors to overcome the blood immune defenses and proliferate. In this review, we highlight our current understanding of determinants of bacterial survival and proliferation in the bloodstream and discuss their interactions with the molecular and cellular components of blood.

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“…The adhesion of SS2 to HBMEC may provide the precondition for SS2 to secrete toxic substances and induce the production of cytokines to change the permeability of BBB (Liu et al, 2021b).…”

Section: Endothelial Cellmentioning

confidence: 99%

Research Progress on the pathogenic mechanism of Streptococcus suis 2

et al. 2021

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Streptococcus suis (S.suis) is an important zoonotic pathogen that can cause many diseases in pigs, such as sepsis, arthritis, endocarditis, and meningitis, of which meningitis is the most serious. There are 35 serotypes, and serotype two is the most virulent. At the same time, Streptococcus suis serotype 2(SS2) can also infect humans, causing severe public health problems. Although SS2 has attracted significant attention worldwide, the research on its pathogenesis is still limited. The adhesion of pathogenic bacteria to the surface of host cells or tissues and its subsequent invasion and diffusion are the critical steps of pathogenic bacteria. Moreover, the interaction between pathogen and host is involved in these processes. Therefore, to study the pathogenic mechanism of pathogenic bacteria is to study the interaction between pathogenic bacteria and host. This paper described several common virulence factors, such as CPS, SLY, MRP, EF, SAO, Srt, FBPS, SadP, and Eno. Under the actions of virulence factors, SS2 adheres and colonizes to the mucosal and epithelial surface of host cells. Then SS2 invades into deeper tissues and bloodstream. If SS2 in the blood does not cause fatal sepsis, It can go to the third stage. The third stage is to cross the BBB and access the CNS and ultimately causes meningitis. During pathogenesis, SS2 interacts with multiple host cells, such as neutrophils, macrophages, epithelial cells, and microvascular endothelial cells to evade the innate or adaptive immunity of the host.

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Stk and Stp1 participate in Streptococcus suis serotype 2 pathogenesis by regulating capsule thickness and translocation of certain virulence factors

Cited by 8 publications

References 38 publications

Inhibitors targeting the autophosphorylation of serine/threonine kinase of Streptococcus suis show potent antimicrobial activity

Inhibitors targeting the autophosphorylation of serine/threonine kinase of Streptococcus suis show potent antimicrobial activity

Determinants of bacterial survival and proliferation in blood

Research Progress on the pathogenic mechanism of Streptococcus suis 2

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