scholarly journals Opacification Domain of Serum Opacity Factor Inhibits Beta-Hemolysis and Contributes to Virulence ofStreptococcus pyogenes

mSphere ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Luchang Zhu ◽  
Randall J. Olsen ◽  
James M. Musser
Keyword(s):  
High Density Lipoprotein ◽  
Virulence Factors ◽  
Streptococcus Pyogenes ◽  
Parental Strain ◽  
Density Lipoprotein ◽  
Binding Domain ◽  
Human Pathogen ◽  
Content Type ◽  
Serum Opacity Factor ◽  
Fibronectin Binding

ABSTRACTSerum opacity factor (SOF) is a cell surface virulence factor made by the human pathogenStreptococcus pyogenes. We found thatS. pyogenesstrains with naturally occurring truncation mutations in thesofgene have markedly enhanced beta-hemolysis. Moreover, deletion of thesofgene in a SOF-positive parental strain resulted in significantly increased beta-hemolysis. Together, these observations suggest that SOF is an inhibitor of beta-hemolysis. SOF has two major functional domains, including an opacification domain and a fibronectin-binding domain. Using a SOF-positive serotype M89S. pyogenesparental strain and a panel of isogenic mutant derivative strains, we evaluated the relative contribution of each SOF functional domain to beta-hemolysis inhibition and bacterial virulence. We found that the opacification domain, rather than the fibronectin-binding domain, is essential for SOF-mediated beta-hemolysis inhibition. The opacification domain, but not the fibronectin-binding domain of SOF, also contributed significantly to virulence in mouse models of bacteremia and necrotizing myositis. Inasmuch as the opacification domain of SOF is known to interact avidly with host high-density lipoprotein (HDL), we speculate that SOF-HDL interaction is an important process underlying SOF-mediated beta-hemolysis inhibition and SOF-mediated virulence.IMPORTANCEStreptococcus pyogenesis a major human pathogen causing more than 700 million infections annually. As a successful pathogen,S. pyogenesproduces many virulence factors that facilitate colonization, proliferation, dissemination, and tissue damage. Serum opacity factor (SOF), an extracellular protein, is one of the virulence factors made byS. pyogenes. The underlying mechanism of how SOF contributes to virulence is not fully understood. SOF has two major features: (i) it opacifies host serum by interacting with high-density lipoprotein, and (ii) it inhibits beta-hemolysis on blood agar. In this study, we demonstrate that the domain of SOF essential for opacifying serum is also essential for SOF-mediated beta-hemolysis inhibition and SOF-mediated virulence. Our results shed new light on the molecular mechanisms of SOF-host interaction.

Association of plant-based diets with lipid profile and anthropometric indices: a cross-sectional study

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Mohadese Borazjani ◽  
Mehran Nouri ◽  
Kamesh Venkatakrishnane ◽  
Maryam Najafi ◽  
Shiva Faghih
Keyword(s):  
High Density Lipoprotein ◽  
Lipid Profile ◽  
Density Lipoprotein ◽  
Cross Sectional Study ◽  
Lipoprotein Cholesterol ◽  
Healthy Plant ◽  
Sectional Study ◽  
Anthropometric Indices ◽  
Cross Sectional ◽  
Content Type

Purpose Plant-based diets have been related to decreasing morbidity and mortality of many non-communicable diseases. The purpose of this study was to investigate the relationship between plant-based diets and lipid profiles and anthropometric indices. Design/methodology/approach This cross-sectional study was performed on 236 men and women selected from Shiraz health-care centers. This study used a 168-item food frequency questionnaire to calculate plant-based diet index (PDI), healthy plant-based diet index (hPDI) and unhealthy plant-based diet index (uPDI). Total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol and triglycerides were measured. Furthermore, body mass index, a body shape index and conicity index (CI) were calculated after measuring weight, height and waist circumference. Findings Higher score of PDI was significantly related to higher triglycerides level (OR = 2.16; 95% CI: 1.04, 4.48; P = 0.03). In the fully adjusted model, there was a significant association between ABSI and hPDI (OR = 4.88; 95% CI: 1.17, 20.24; P = 0.03). A significant inverse association was observed between uPDI and high-density lipoprotein (HDL) (OR = 0.45; 95% CI = 0.21, 0.98; P = 0.03). Also, this study found a decreasing, but insignificant trend in relation of ABSI (OR = 0.72; 95% CI = 0.22, 2.34) and CI (OR = 0.41; 95% CI = 0.06, 0.56) with PDI. Research limitations/implications Further studies are needed to explore the association of PDI with anthropometric indices and lipid profile and also to assess the potential causality of the observed associations. Plant-based diets according to their contents could affect triglycerides, HDL and anthropometric properties. Practical implications Hence, dietitians should consider the findings of this study such as the inverse effect of unhealthy plant-based diets on HDL and the relation between healthy plant-based diets and WC and abdominal obesity. Originality/value This study showed that adherence to a plant-based diet was related to higher triglycerides levels. Also, uPDI was inversely associated with HDL level. Furthermore, participants who adhered more to a healthy plant-based diet had higher abdominal adiposity.

scholarly journals Derivatives of Plant Phenolic Compound Affect the Type III Secretion System of Pseudomonas aeruginosa via a GacS-GacA Two-Component Signal Transduction System

2011 ◽  
Vol 56 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Akihiro Yamazaki ◽  
Jin Li ◽  
Quan Zeng ◽  
Devanshi Khokhani ◽  
William C. Hutchins ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phenolic Compounds ◽  
Virulence Factors ◽  
Type Iii Secretion ◽  
Small Rnas ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Human Pathogen ◽  
Content Type ◽  
Type Iii

ABSTRACTAntibiotic therapy is the most commonly used strategy to control pathogenic infections; however, it has contributed to the generation of antibiotic-resistant bacteria. To circumvent this emerging problem, we are searching for compounds that target bacterial virulence factors rather than their viability.Pseudomonas aeruginosa, an opportunistic human pathogen, possesses a type III secretion system (T3SS) as one of the major virulence factors by which it secretes and translocates T3 effector proteins into human host cells. The fact that this human pathogen also is able to infect several plant species led us to screen a library of phenolic compounds involved in plant defense signaling and their derivatives for novel T3 inhibitors. Promoter activity screening ofexoS, which encodes a T3-secreted toxin, identified two T3 inhibitors and two T3 inducers ofP. aeruginosaPAO1. These compounds alterexoStranscription by affecting the expression levels of the regulatory small RNAs RsmY and RsmZ. These two small RNAs are known to control the activity of carbon storage regulator RsmA, which is responsible for the regulation of the key T3SS regulator ExsA. As RsmY and RsmZ are the only targets directly regulated by GacA, our results suggest that these phenolic compounds affect the expression ofexoSthrough the GacSA-RsmYZ-RsmA-ExsA regulatory pathway.

scholarly journals The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus

2015 ◽  
Vol 197 (23) ◽  
pp. 3720-3730 ◽  
Author(s):  
Jessica L. Danger ◽  
Nishanth Makthal ◽  
Muthiah Kumaraswami ◽  
Paul Sumby
Keyword(s):  
Cell Surface ◽  
Virulence Factors ◽  
Binding Proteins ◽  
Mrna Translation ◽  
Regulatory Rna ◽  
Collagen Binding ◽  
Content Type ◽  
Small Regulatory Rna ◽  
Group A ◽  
Fibronectin Binding

ABSTRACTThe group AStreptococcus(GAS;Streptococcus pyogenes) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to theprtF1andprtF2mRNAs within their 5′ untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and theprtF1andprtF2mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection.IMPORTANCEMore than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small RNA FasX. In addition to identifying that FasX reduces the abundance of the cell surface-located fibronectin-binding proteins PrtF1/2, fibronectin is present in high abundance in human tissues, and we have determined the mechanism behind this regulation. Importantly, as FasX is the only mechanistically characterized regulatory RNA in GAS, it serves as a model RNA in this and related pathogens.

scholarly journals The Streptococcal Protease SpeB Antagonizes the Biofilms of the Human Pathogen Staphylococcus aureus USA300 through Cleavage of the Staphylococcal SdrC Protein

2020 ◽  
Vol 202 (11) ◽  
Author(s):  
Katelyn E. Carothers ◽  
Zhong Liang ◽  
Jeffrey Mayfield ◽  
Deborah L. Donahue ◽  
Mijoon Lee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Proteolytic Activity ◽  
Streptococcus Pyogenes ◽  
Human Pathogen ◽  
Content Type ◽  
Functional Studies ◽  
Human Proteins ◽  
Group A ◽  
Biofilm Disruption

ABSTRACT Streptococcus pyogenes, or group A Streptococcus (GAS), is both a pathogen and an asymptomatic colonizer of human hosts and produces a large number of surface-expressed and secreted factors that contribute to a variety of infection outcomes. The GAS-secreted cysteine protease SpeB has been well studied for its effects on the human host; however, despite its broad proteolytic activity, studies on how this factor is utilized in polymicrobial environments are lacking. Here, we utilized various forms of SpeB protease to evaluate its antimicrobial and antibiofilm properties against the clinically important human colonizer Staphylococcus aureus, which occupies niches similar to those of GAS. For our investigation, we used a skin-tropic GAS strain, AP53CovS+, and its isogenic ΔspeB mutant to compare the production and activity of native SpeB protease. We also generated active and inactive forms of recombinant purified SpeB for functional studies. We demonstrate that SpeB exhibits potent biofilm disruption activity at multiple stages of S. aureus biofilm formation. We hypothesized that the surface-expressed adhesin SdrC in S. aureus was cleaved by SpeB, which contributed to the observed biofilm disruption. Indeed, we found that SpeB cleaved recombinant SdrC in vitro and in the context of the full S. aureus biofilm. Our results suggest an understudied role for the broadly proteolytic SpeB as an important factor for GAS colonization and competition with other microorganisms in its niche. IMPORTANCE Streptococcus pyogenes (GAS) causes a range of diseases in humans, ranging from mild to severe, and produces many virulence factors in order to be a successful pathogen. One factor produced by many GAS strains is the protease SpeB, which has been studied for its ability to cleave and degrade human proteins, an important factor in GAS pathogenesis. An understudied aspect of SpeB is the manner in which its broad proteolytic activity affects other microorganisms that co-occupy niches similar to that of GAS. The significance of the research reported herein is the demonstration that SpeB can degrade the biofilms of the human pathogen Staphylococcus aureus, which has important implications for how SpeB may be utilized by GAS to successfully compete in a polymicrobial environment.

scholarly journals The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated Streptococcus pyogenes Infections

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Jeffrey A. Freiberg ◽  
Yoann Le Breton ◽  
Janette M. Harro ◽  
Devon L. Allison ◽  
Kevin S. McIver ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Antibiotic Treatment ◽  
Streptococcus Pyogenes ◽  
Bacterial Infections ◽  
Bacterial Species ◽  
Arginine Deiminase ◽  
Antibiotic Tolerance ◽  
Human Pathogen ◽  
Biofilm Growth ◽  
Content Type

ABSTRACT Bacterial biofilms are responsible for a variety of serious human infections and are notoriously difficult to treat due to their recalcitrance to antibiotics. Further work is necessary to elicit a full understanding of the mechanism of this antibiotic tolerance. The arginine deiminase (ADI) pathway is responsible for bacterial pH maintenance and is highly expressed during biofilm growth in multiple bacterial species. Using the group A Streptococcus (GAS) as a model human pathogen, the ADI pathway was demonstrated to contribute to biofilm growth. The inability of antibiotics to reduce GAS populations when in a biofilm was demonstrated by in vitro studies and a novel animal model of nasopharyngeal infection. However, disruption of the ADI pathway returned GAS biofilms to planktonic levels of antibiotic sensitivity, suggesting the ADI pathway is influential in biofilm-related antibiotic treatment failure and provides a new strategic target for the treatment of biofilm infections in GAS and potentially numerous other bacterial species. IMPORTANCE Biofilm-mediated bacterial infections are a major threat to human health because of their recalcitrance to antibiotic treatment. Through the study of Streptococcus pyogenes, a significant human pathogen that is known to form antibiotic-tolerant biofilms, we demonstrated the role that a bacterial pathway known for responding to acid stress plays in biofilm growth and antibiotic tolerance. This not only provides some insight into antibiotic treatment failure in S. pyogenes infections but also, given the widespread nature of this pathway, provides a potentially broad target for antibiofilm therapies. This discovery has the potential to impact the treatment of many different types of recalcitrant biofilm infections.

scholarly journals Function of the Fibronectin-Binding Serum Opacity Factor of Streptococcus pyogenes in Adherence to Epithelial Cells

2004 ◽  
Vol 72 (7) ◽  
pp. 4302-4308 ◽  
Author(s):  
Sonja Oehmcke ◽  
Andreas Podbielski ◽  
Bernd Kreikemeyer
Keyword(s):  
Epithelial Cells ◽  
Streptococcus Pyogenes ◽  
Binding Proteins ◽  
Dissociation Constants ◽  
Cell Adherence ◽  
Latex Beads ◽  
Serum Opacity Factor ◽  
Order Of Magnitude ◽  
Fibronectin Binding ◽  
Adherence Inhibition

ABSTRACT The serum opacity factor (SOF) of Streptococcus pyogenes is a serotyping tool and pathogenesis factor. Using SOF-coated latex beads in cell adherence assays and antiserum directed against SOF in S. pyogenes-HEp-2 cell adherence inhibition experiments, we demonstrate SOF involvement in the fibronectin-mediated adherence of S. pyogenes to epithelial cells. SOF exclusively targets the 30-kDa N-terminal region of fibronectin. The interaction revealed association and dissociation constants 1 order of magnitude lower than those of other S. pyogenes fibronectin-binding proteins.

scholarly journals Serum opacity factor is a major fibronectin-binding protein and a virulence determinant of M type 2 Streptococcus pyogenes

1999 ◽  
Vol 32 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Harry S. Courtney ◽  
David L. Hasty ◽  
Yi Li ◽  
Herbert C. Chiang ◽  
Jenny L. Thacker ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Binding Protein ◽  
Virulence Determinant ◽  
Serum Opacity Factor ◽  
Fibronectin Binding Protein ◽  
Fibronectin Binding
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