Golden pigment STX is regarded as an important feature of the human pathogen S. In response to changing host environments, S. It makes sense that both pigmented and non-pigmented S. Thus, the block of the STX biosynthesis process has proposed as an alternative anti-virulence therapy, in which crtM and crtN are target for drugs used in the treatment of infections caused by pigmented S.
These results are corresponded with previous reports that not all the non-pigmented isolates are lack of integrated crtN or crtM. Since the production of them are regulated by the metabolic pathways including purine biosynthesis, the TCA cycle, and even oxidative phosphorylation Marshall and Wilmoth, These associated genes did exist but would usually not normally express.
Staphylococcus aureus can produce various virulence factors, related to severe pneumonia, soft tissue infections and staphylococcal scalded skin syndrome. Among those virulence factors, heat-stable enterotoxin SE , is undoubtedly one of the primary causes of staphylococcal food poisoning Becker et al.
Before the sey was added in , there were 21 identified SEs and staphylococcal-like enterotoxin SEl genes, namely sea to see, seg to sev Xie et al. Because lots of virulence genes are coordinately regulated in S. The detection of virulence factors can not only prevent the genetic diversity, but also indicate the different pathogenicity of S. In this study, these examined S. In comparison, pigmented isolates were the dominant isolates that carried the seh gene.
While in general, there was no significant difference of virulence factors between the two phenotype groups, which demonstrated that their pigment phenotype had no correlation with the presence of virulence factors as well as their pathogenicity.
The pathogenesis of staphylococcal infections is a multifactorial process. It is on account of the production of various virulence factors, which are controlled by multiple regulatory systems and affected by environmental and nutritional signals Somerville and Proctor, In order to adapt to the incessant environmental changes for their own survival and causing infection, bacterium can adjust the high degree of variability in the production of toxic genes by a complex network modulated by factors such as the agr locus RNAIII , SarA, and SigB Clauditz et al.
Staphylococcus argenteus is a novel Staphylococcus species, which is closely associated with S. This species presents a non-pigmented phenotype on chocolate agar plates due to the lack of the gene cluster responsible for STX production Argudin et al. For comparison, 4 S. The choice of the 24 S. As shown in Table 1 and Figure 2 , the pigmented and non-pigmented isolates were selected in pair from the same STs to ensure the equivalence between their phenotype and genotype.
All the STs conferring both pigmented and non-pigmented isolates have been covered in the tested isolates. The genotypes of the 4 S. Since there is a phylogenetic difference between S. Thus, it was regarded that the lack of STX might reduce the virulence of isolates to some extent. While our findings suggest that some non-pigmented S. Although the reasons for the high virulence of non-pigmented isolates remain to be elucidated, our finding demonstrated that STX is not necessary for infection in the lineage of S.
There are lots of studies that aim to evaluate the different virulence between pigmented and non-pigmented strains. Some studies seem to support the hypothesis, for example, non-pigmented mutants had been used to compare with the corresponding wild-type WT strains, finding that it is more susceptible to desiccation and to linolenic acid Wieland, ; compared with the WT bacterium, a S.
For example, Tong et al. Thus, it is unclear that if the virulence properties of non-pigmented S. All in one, we came to the conclusion that there is no direct relationship between the presence of STX and genotype as well as the toxicity of the naturally isolated S. Non-pigmented isolates have the similar virulence with pigmented ones.
Although blocking the biosynthesis of STX has been put forward as a novel potential anti-virulence strategy, the non-pigmented S. Thus it is reasonable to speculate that for better therapeutic effect against S. JZ completed the quantification of pigment, MLST and spa typing, detection of virulence factors, and murine infection assay. FJ helped to finish the quantification of pigment and detection of virulence factors.
CS designed the project, completed the data analysis, and prepared the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Wang, Y. A dose and time dependency was observed in the production of IL-8 following stimulation with 0. Severe invasive S. Bacterial invasion and disease pathogenesis is a complex process that is achieved through numerous virulence factors. Invasive S.
However, the role of the S. Interestingly, the cov or csr system as a major regulator of S. A recent study by Sendi et al. With increasing incubation time from 0. In contrast to this, the nonhemolytic strain caused damage of eukaryotic cells only at long-term incubation 24 h which may be caused by the induction of apoptosis [20] [21].
To investigate if an improved survival of the nonhemolytic strain could also be observed in the interaction with granulocytes as described by Sendi et al. In these settings, significantly higher numbers of the nonhemolytic strains were recovered which is compatible with the results of Sendi et al.
While the major phenotypic difference between the two strains we tested is the loss of hemolysis in the mutant strain, we can currently not exclude the possibility that the mutation of the hemolysin transporter causes an altered expression of other virulence determinants, which may contribute to the increased intracellular persistence, we observed.
It is intriguing to see that an important virulence regulator of S. The clinical observation that cov mutation and resulting hyperhemolysis are associated with devastating fulminant invasive disease offers a possible explanation for this phenomenon [8].
Maximal expression of virulence factors does not appear to be beneficial in all stages of the course of an infection. The improved survival within professional macrophages may provide advantages like the escape from antibody attacks or the use of these host cells in the sense of a Trojan horse, as it has been observed in other pathogens [22] [23]. A recent publication describing the increased expression of the cov regulator in S.
While investigating the survival of S. Littmann et al. Recovery of higher numbers of the pneumolysin-deficient strain from human dendritic cells as compared to the wild type strain seems to be advantageous because the hemolytic activity of pneumolysin was not found to be essential for invasive disease in their experimental setup.
Using a murine model of pneumococcal bacteremia, Harvey et al. Independent observations from both groups about the pneumolysin expression dependent survival of S. In our experiments, we could demonstrate that the survival of S.
We were able to show that entry of S. A similar finding was made by Valentin-Weigand et al. Our results also support the findings of Fettuciari et al. Our fluorescence microscopy data clearly distinguishes between intracellular and extracellular bacteria.
However, the current study does not address the location of bacteria within the macrophages. Previous electron micrograph and fluorescence microscopic studies on various GBS serotypes have reported the location of GBS within the membrane-bound vacuole in a variety of host-cell types, including epithelial cells [17] , endothelial cells [30] [31] , dendritic cells [32] and macrophages [33] [29] [34]. In Listeria monocytogenes , the hemolysin is important in phagosomal escape and hemolysin negative mutants are thus impaired in intracellular survival [35].
However, in a recent investigation of the subcellular localization of S. The vast majority of S. The strength and efficiency of the immune response of the host is dependent on the release of cytokines. Previous literature has shown that group B streptococci stimulate the release of various cytokines and chemokines from human mononuclear cells and murine macrophages [36] [37].
The chemokine IL-8 is an important marker of bacterial infections. However, we could not find a significant difference in the release of IL-8 by the hemolytic and nonhemolytic bacteria.
Use of different S. In addition, the higher number of nonhemolytic bacteria may have compensated for the IL-8 production and therefore a comparable release of IL-8 is observed. In this regard the gram positive cell wall is a likely proinflammatory candidate.
Previous studies have shown the effect of individual S. Compatible with these results, we found that the presence of cell wall components from both hemolytic and nonhemolytic bacteria induces similar levels of IL-8 in a concentration dependent manner. In conclusion, we were able to show that the absence of S. This explanation is partly supported by the previous report indicating that the S. Two-component regulatory systems allow bacteria to adapt to changing environmental conditions.
In line with this, the S. Our data support the hypothesis that invasive S. Analyzed the data: AS LH. Wrote the paper: AS BS. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Abstract S. Introduction The Gram positive pathogen Streptococcus agalactiae or group B streptococcus GBS is the leading microbial agent of neonatal pneumonia, sepsis and meningitis presenting as early or late-onset disease in human newborns [1] [2].
Download: PPT. Isolation of Human Peripheral Blood Granulocytes Peripheral blood was collected by venipuncture from healthy adult volunteers who gave informed written consent to donate blood specifically for the purpose of the study.
Intracellular S. Visualizing Intracellular S. Cell Wall Preparations Purified cell walls were prepared as described elsewhere [15]. Figure 1. Survival of S. Figure 2. Figure 3. Effect of Cytochalasin D on invasion capacity of S. Microscopic Evaluation of Intracellular S. Figure 4. Microscopic evaluation of intracellular S. Figure 5. Cytokine Induction by Type Ia Group B Streptococci The strength and efficiency of the immune response of the host is dependent on the release of proinflammatory cytokines.
Figure 6. Induction of Proinflammatory Cytokines by S. Figure 7. Similar IL-8 expression pattern in response to purified cell wall preparations from hemolytic and nonhemolytic S.
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