A serine/threonine phosphatase 1 of Streptococcus suis type 2 is an important virulence factor

Abstract

Streptococcus suis is regarded as one of the major pathogens of pigs, and Streptococcus suis type 2 (SS2) is considered a zoonotic bacterium based on its ability to cause meningitis and streptococcal toxic shock-like syndrome in humans. Many bacterial species contain genes encoding serine/threonine protein phosphatases (STPs) responsible for dephosphorylation of their substrates in a single reaction step. This study investigated the role of stp1 in the pathogenesis of SS2. An isogenic stp1 mutant (Δstp1) was constructed from SS2 strain ZJ081101. The Δstp1 mutant exhibited a significant increase in adhesion to HEp-2 and bEnd.3 cells as well as increased survival in RAW264.7 cells, as compared to the parent strain. Increased survival in macrophage cells might be related to resistance to reactive oxygen species since the Δstp1 mutant was more resistant than its parent strain to paraquat-induced oxidative stress. However, compared to parent strain virulence, deletion of stp1 significantly attenuated virulence of SS2 in mice, as shown by the nearly double lethal dose 50 value and the lower bacterial load in organs and blood in the murine model. We conclude that Stp1 has an essential role in SS2 virulence.

Streptococcus suis DivIVA Protein Is a Substrate of Ser/Thr Kinase STK and Involved in Cell Division Regulation

“…S. suis 2 utilizes SodA for survival not only by scavenging ROS but also by alleviating the host autophagic responses due to ROS stimulation (Fang et al, 2015 ). The inactivation of a serine/threonine phosphatase (stp1) increases S. suis 2 resistance to oxidative stress and survival in macrophage cells (Fang et al, 2017 ). In the present study, the phosphorylation of SodA was abolished in the stk mutant.…”

The Redox-Sensing Regulator Rex Contributes to the Virulence and Oxidative Stress Response of Streptococcus suis Serotype 2

“…Once S. suis reaches deep tissues and/or the bloodstream, phagocytic cells play a pivotal role in the host defense against these invading pathogens during infection (Fang et al, 2017 ). Phagocytosis and intracellular survival assays were performed in RAW264.7 cells to assess the role of SsRex in the context of S. suis –phagocyte interactions.…”

“…To deal with these hostile environments, pathogenic bacteria have evolved or acquired regulatory networks to sense and respond to environmental signals by modulating the expression of related genes. In S. suis , the signal regulatory systems contained within the two-component systems (TCSs) such as SalK/R (Li et al, 2008 ), NisKR (Xu et al, 2014 ), CiaRH (Li et al, 2011 ), and SsSTK/SsSTP (Zhu et al, 2011 , 2014 ; Fang et al, 2017 ; Zhang et al, 2017 ), stand-alone regulators (SARs) such as CcpA (Willenborg et al, 2011 , 2014 ) and Rgg (Zheng et al, 2011 ), and other regulators such as CodY (Feng et al, 2016 ), PerR (Zhang et al, 2012 ), AdcR , and Fur (Aranda et al, 2010 ) have been shown to be involved in bacterial metabolism and virulence. To gain further insight into the global regulatory networks of SS2, the role of other uncharacterized regulators should be investigated.…”

Involvement of Various Enzymes in the Physiology and Pathogenesis of Streptococcus suis

“…Copper efflux [20] PmtA Ferrous iron and cobalt efflux, tolerance to hydrogen peroxide-induced oxidative stress [21] MsmK Utilization of multiple carbohydrates, pathogenesis [22,23] Ide Ssuis Degradation of porcine IgM, complement evasion [24][25][26] IgdE Degradation of porcine IgG [27] IgA1 protease/ZmpC Degradation of human IgA1, pathogenesis 1 [28][29][30][31] eSTK Maintaining bacterial morphology, tolerance to stresses, pathogenesis [32][33][34] eSTP Virulence, cell adhesion, and immune evasion 2 [35,36] SspA-1 Virulence, trigger of proinflammatory cytokines [37,38] SspA-2 Pathogenesis, proinflammatory response in macrophages [39][40][41] Superoxide dismutase Oxidative stress resistance, virulence [42,43] NADH oxidase Tolerance to oxidative stress, virulence [44,45] SsnA Degradation of human and porcine neutrophil extracellular traps, pathogenesis [46][47][48] EndAsuis Degradation of neutrophil extracellular traps [49] Enolase Binding of extracellular matrix components, pathogenesis [50][51][52][53][54][55][56][57][58] LuxS Growth, biofilm formation, capsule synthesis, hydrogen peroxide resistance, resistance to fluoroquinolones, pathogenesis [59]…”

“…The role of eSTP in cell adhesion and immune evasion seems to be contradictory between S. suis 2 and 9. Given that eSTP shares high level of homology between S. suis 2 and 9 [ 36 ], further studies should be performed to determine whether the opposite conclusions are attributable to the different serotypes.…”