scholarly journals Staphylococcus aureus SasA Is Responsible for Binding to the Salivary Agglutinin gp340, Derived from Human Saliva

2013 ◽  
Vol 81 (6) ◽  
pp. 1870-1879 ◽  
Author(s):  
Kenji Kukita ◽  
Miki Kawada-Matsuo ◽  
Takahiko Oho ◽  
Mami Nagatomo ◽  
Yuichi Oogai ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Oral Cavity ◽  
Surface Protein ◽  
Human Saliva ◽  
Oral Bacteria ◽  
Surface Plasmon Resonance Analysis ◽  
Content Type ◽  
Acetylneuraminic Acid ◽  
Resonance Analysis ◽  
Content Factor

ABSTRACTStaphylococcus aureusis a major human pathogen that can colonize the nasal cavity, skin, intestine, and oral cavity as a commensal bacterium. gp340, also known as DMBT1 (deleted in malignant brain tumors 1), is associated with epithelial differentiation and innate immunity. In the oral cavity, gp340 induces salivary aggregation with several oral bacteria and promotes bacterial adhesion to tissues such as the teeth and mucosa.S. aureusis often isolated from the oral cavity, but the mechanism underlying its persistence in the oral cavity remains unclear. In this study, we investigated the interaction betweenS. aureusand gp340 and found thatS. aureusinteracts with saliva- and gp340-coated resin. We then identified theS. aureusfactor(s) responsible for binding to gp340. The cell surface protein SasA, which is rich in basic amino acids (BR domain) at the N terminus, was responsible for binding to gp340. Inactivation of thesasAgene resulted in a significant decrease inS. aureusbinding to gp340-coated resin. Also, recombinant SasA protein (rSasA) showed binding affinity to gp340, which was inhibited by the addition ofN-acetylneuraminic acid. Surface plasmon resonance analysis showed that rSasA significantly bound to the NeuAcα(2-3)Galβ(1-4)GlcNAc structure. These results indicate that SasA is responsible for binding to gp340 via theN-acetylneuraminic acid moiety.

scholarly journals Host Defense Proteins Derived from Human Saliva Bind to Staphylococcus aureus

2013 ◽  
Vol 81 (4) ◽  
pp. 1364-1373 ◽  
Author(s):  
Seok-Mo Heo ◽  
Kyoung-Soo Choi ◽  
Latif A. Kazim ◽  
Molakala S. Reddy ◽  
Elaine M. Haase ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Oral Cavity ◽  
Host Defense ◽  
Bacterial Colonization ◽  
Human Saliva ◽  
Salivary Protein ◽  
Salivary Proteins ◽  
Staphylococcal Protein A ◽  
Defense Proteins ◽  
Content Type

ABSTRACTProteins in human saliva are thought to modulate bacterial colonization of the oral cavity. Yet, information is sparse on how salivary proteins interact with systemic pathogens that transiently or permanently colonize the oral environment.Staphylococcus aureusis a pathogen that frequently colonizes the oral cavity and can cause respiratory disease in hospitalized patients at risk. Here, we investigated salivary protein binding to this organism upon exposure to saliva as a first step toward understanding the mechanism by which the organism can colonize the oral cavity of vulnerable patients. By using fluorescently labeled saliva and proteomic techniques, we demonstrated selective binding of major salivary components byS. aureusto include DMBT1gp-340, mucin-7, secretory component, immunoglobulin A, immunoglobulin G, S100-A9, and lysozyme C. Biofilm-grownS. aureusstrains bound fewer salivary components than in the planctonic state, particularly less salivary immunoglobulins. A corresponding adhesive component on theS. aureussurface responsible for binding salivary immunoglobulins was identified as staphylococcal protein A (SpA). However, SpA did not mediate binding of nonimmunoglobulin components, including mucin-7, indicating the involvement of additional bacterial surface adhesive components. These findings demonstrate that a limited number of salivary proteins, many of which are associated with various aspects of host defense, selectively bind toS. aureusand lead us to propose a possible role of saliva in colonization of the human mouth by this pathogen.

scholarly journals Polyphosphate-Accumulating Bacteria: Potential Contributors to Mineral Dissolution in the Oral Cavity

2018 ◽  
Vol 84 (7) ◽  
Author(s):  
Ashley A. Breiland ◽  
Beverly E. Flood ◽  
Julia Nikrad ◽  
John Bakarich ◽  
Matthew Husman ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Acid Production ◽  
Phosphate Uptake ◽  
Model Organism ◽  
Oral Bacteria ◽  
Mineral Dissolution ◽  
Public Health Issue ◽  
Saturation State ◽  
Content Type ◽  
Carious Lesions

ABSTRACT Bacteria that accumulate polyphosphates have previously been shown to dynamically influence the solubility of phosphatic minerals in marine settings and wastewater. Here, we show that dental plaque, saliva, and carious lesions all contain abundant polyphosphate-accumulating bacteria. Saturation state modeling results, informed by phosphate uptake experiments using the model organism Lactobacillus rhamnosus , which is known to inhabit advanced carious lesions, suggest that polyphosphate accumulation can lead to undersaturated conditions with respect to hydroxyapatite under some oral cavity conditions. The cell densities of polyphosphate-accumulating bacteria we observed in some regions of oral biofilms are comparable to those that produce undersaturated conditions (i.e., those that thermodynamically favor mineral dissolution) in our phosphate uptake experiments with L. rhamnosus . These results suggest that the localized generation of undersaturated conditions by polyphosphate-accumulating bacteria constitutes a new potential mechanism of tooth dissolution that may augment the effects of metabolic acid production. IMPORTANCE Dental caries is a serious public health issue that can have negative impacts on overall quality of life and oral health. The role of oral bacteria in the dissolution of dental enamel and dentin that can result in carious lesions has long been solely ascribed to metabolic acid production. Here, we show that certain oral bacteria may act as a dynamic shunt for phosphate in dental biofilms via the accumulation of a polymer known as polyphosphate—potentially mediating phosphate-dependent conditions such as caries (dental decay).

scholarly journals Phase IIa Study of the Immunogenicity and Safety of the Novel Staphylococcus aureus Vaccine V710 in Adults with End-Stage Renal Disease Receiving Hemodialysis

2012 ◽  
Vol 19 (9) ◽  
pp. 1509-1516 ◽  
Author(s):  
Moustafa Moustafa ◽  
George R. Aronoff ◽  
Chandra Chandran ◽  
Jonathan S. Hartzel ◽  
Steven S. Smugar ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Geometric Mean ◽  
Surface Protein ◽  
Chronic Hemodialysis ◽  
Content Type ◽  
Primary Hypothesis ◽  
Stage Renal Disease ◽  
End Stage

ABSTRACTBacteremia is the second leading cause of death in patients with end-stage renal disease who are on hemodialysis. A vaccine eliciting long-term immune responses againstStaphylococcus aureusin patients on chronic hemodialysis may reduce the incidence of bacteremia and its complications in these patients. V710 is a vaccine containing iron surface determinant B (IsdB), a highly conservedS. aureussurface protein, which has been shown to be immunogenic in healthy subjects. In this blinded phase II immunogenicity study, 206 chronic hemodialysis patients between the ages of 18 and 80 years old were randomized to receive 60 μg V710 (with or without adjuvant), 90 μg V710 (with adjuvant), or a placebo in various combinations on days 1, 28, and 180. All 201 vaccinated patients were to be followed through day 360. The primary hypothesis was that at least 1 of the 3 groups receiving 2 V710 doses on days 1 and 28 would have a ≥2.5 geometric mean fold rise (GMFR) in anti-IsdB IgG titers over the baseline 28 days after the second vaccination (day 56). At day 56, all three groups receiving 2 doses of V710 achieved a ≥2.5 GMFR in anti-IsdB antibodies compared to the baseline (Pvalues of <0.001 for all 3 groups), satisfying the primary immunogenicity hypothesis. None of the 33 reported serious adverse experiences were considered vaccine related by the investigators. V710 induced sustained antibody responses for at least 1 year postvaccination in patients on chronic hemodialysis.

scholarly journals MgrA Negatively Impacts Staphylococcus aureus Invasion by Regulating Capsule and FnbA

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Mei G. Lei ◽  
Dereje D. Gudeta ◽  
Thanh T. Luong ◽  
Chia Y. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Hela Cells ◽  
Biological Significance ◽  
Surface Protein ◽  
Surface Proteins ◽  
Multiple Gene ◽  
Content Type ◽  
Fibronectin Binding Protein ◽  
Different Levels ◽  
Complex Regulatory Network

ABSTRACT Virulence genes are regulated by a complex regulatory network in Staphylococcus aureus. Some of the regulators are global in nature and affect many downstream genes. MgrA is a multiple-gene regulator that has been shown to activate genes involved in capsule biosynthesis and repress surface protein genes. The goal of this study was to demonstrate the biological significance of MgrA regulation of capsule and surface proteins. We found that strain Becker possessed one fibronectin-binding protein, FnbA, and that FnbA was the predominant protein involved in invasion of nonphagocytic HeLa cells. By genetic analysis of strains with different amounts of capsule, we demonstrated that capsule impeded invasion of HeLa cells by masking the bacterial cell wall-anchored protein FnbA. Using variants with different levels of mgrA transcription, we further demonstrated that MgrA negatively impacted invasion by activating the cap genes involved in capsule biosynthesis and repressing the fnbA gene. Thus, we conclude that MgrA negatively impacts cell invasion of S. aureus Becker by promoting capsule and repressing FnbA.

Salivary Histatin 5 and its Similarities to the Other Antimicrobial Proteins in Human Saliva

2000 ◽  
Vol 14 (1) ◽  
pp. 16-21 ◽  
Author(s):  
M. Edgerton ◽  
S.E. Koshlukova
Keyword(s):  
Antimicrobial Activity ◽  
Oral Cavity ◽  
Human Saliva ◽  
Oral Bacteria ◽  
Defense System ◽  
Antimicrobial Proteins ◽  
Cationic Proteins ◽  
Histatin 5 ◽  
Host Defense System ◽  
Bacteria And Fungi

Non-immune salivary proteins-including lactoperoxidase, lysozyme, lactoferrin, and histatins-are key components of the innate host defense system in the oral cavity. Many antimicrobial proteins contain multiple functional domains, with the result that one protein may have more than one mechanism of antimicrobial activity. These domains may be separated by proteolytic cleavage, creating smaller proteins with functional antimicrobial activity in saliva as described for lysozyme, lactoferrin, and histatins. These small cationic proteins then exert cytotoxic activity to oral bacteria and fungi. Salivary histatin 5 initiates killing of C. albicans through binding to yeast membrane proteins and non-lytic release of cellular ATP. Extracellular ATP may then activate fungal ATP receptors to induce ultimate cell death. This mechanism for fungal cytotoxicity may be shared by other antimicrobial cationic proteins. Microbicidal domains of salivary and host innate proteins should be considered as potential therapeutic agents in the oral cavity.

scholarly journals Murein Hydrolase LytF of Streptococcus sanguinis and the Ecological Consequences of Competence Development

2017 ◽  
Vol 83 (24) ◽  
Author(s):  
Nyssa Cullin ◽  
Sylvio Redanz ◽  
Kirsten J. Lampi ◽  
Justin Merritt ◽  
Jens Kreth
Keyword(s):  
Dental Caries ◽  
Oral Cavity ◽  
Cell Morphology ◽  
Biofilm Formation ◽  
Oral Bacteria ◽  
Tooth Surface ◽  
Content Type ◽  
Streptococcus Sanguinis ◽  
Murein Hydrolase ◽  
Biofilm Development

ABSTRACT The overall health of the oral cavity is dependent on proper homeostasis between health-associated bacterial colonizers and bacteria known to promote dental caries. Streptococcus sanguinis is a health-associated commensal organism, a known early colonizer of the acquired tooth pellicle, and is naturally competent. We have shown that LytF, a competence-controlled murein hydrolase, is capable of inducing the release of extracellular DNA (eDNA) from oral bacteria. Precipitated LytF and purified LytF were used as treatments against planktonic cultures and biofilms. Larger amounts of eDNA were released from cultures treated with protein samples containing LytF. Additionally, LytF could affect biofilm formation and cellular morphology. Biofilm formation was significantly decreased in the lytF-complemented strain, in which increased amounts of LytF are present. The same strain also exhibited cell morphology defects in both planktonic cultures and biofilms. Furthermore, the LytF cell morphology phenotype was reproducible in wild-type cells using purified LytF protein. In sum, our findings demonstrate that LytF can induce the release of eDNA from oral bacteria, and they suggest that, without proper regulation of LytF, cells display morphological abnormalities that contribute to biofilm malformation. In the context of the oral biofilm, LytF may play important roles as part of the competence and biofilm development programs, as well as increasing the availability of eDNA. IMPORTANCE Streptococcus sanguinis, a commensal organism in the oral cavity and one of the pioneer colonizers of the tooth surface, is associated with the overall health of the oral environment. Our laboratory showed previously that, under aerobic conditions, S. sanguinis can produce H2O2 to inhibit the growth of bacterial species that promote dental caries. This production of H2O2 by S. sanguinis also induces the release of eDNA, which is essential for proper biofilm formation. Under anaerobic conditions, S. sanguinis does not produce H2O2 but DNA is still released. Determining how S. sanguinis releases DNA is thus essential to understand biofilm formation in the oral cavity.

scholarly journals Use of a Human-Like Low-Grade Bacteremia Model of Experimental Endocarditis To Study the Role of Staphylococcus aureus Adhesins and Platelet Aggregation in Early Endocarditis

2012 ◽  
Vol 81 (3) ◽  
pp. 697-703 ◽  
Author(s):  
Tiago Rafael Veloso ◽  
Aziz Chaouch ◽  
Thierry Roger ◽  
Marlyse Giddey ◽  
Jacques Vouillamoz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Platelet Aggregation ◽  
Surface Protein ◽  
Infection Process ◽  
Low Grade ◽  
Content Type ◽  
Fibrinogen Binding ◽  
Aggregation Property ◽  
Surface Adhesins

ABSTRACTAnimal models of infective endocarditis (IE) induced by high-grade bacteremia revealed the pathogenic roles ofStaphylococcus aureussurface adhesins and platelet aggregation in the infection process. In humans, however,S. aureusIE possibly occurs through repeated bouts of low-grade bacteremia from a colonized site or intravenous device. Here we used a rat model of IE induced by continuous low-grade bacteremia to explore further the contributions ofS. aureusvirulence factors to the initiation of IE. Rats with aortic vegetations were inoculated by continuous intravenous infusion (0.0017 ml/min over 10 h) with 106CFU ofLactococcus lactispIL253 or a recombinantL. lactisstrain expressing an individualS. aureussurface protein (ClfA, FnbpA, BCD, or SdrE) conferring a particular adhesive or platelet aggregation property. Vegetation infection was assessed 24 h later. Plasma was collected at 0, 2, and 6 h postinoculation to quantify the expression of tumor necrosis factor (TNF), interleukin 1α (IL-1α), IL-1β, IL-6, and IL-10. The percentage of vegetation infection relative to that with strain pIL253 (11%) increased when binding to fibrinogen was conferred onL. lactis(ClfA strain) (52%;P= 0.007) and increased further with adhesion to fibronectin (FnbpA strain) (75%;P< 0.001). Expression of fibronectin binding alone was not sufficient to induce IE (BCD strain) (10% of infection). Platelet aggregation increased the risk of vegetation infection (SdrE strain) (30%). Conferring adhesion to fibrinogen and fibronectin favored IL-1β and IL-6 production. Our results, with a model of IE induced by low-grade bacteremia, resembling human disease, extend the essential role of fibrinogen binding in the initiation ofS. aureusIE. Triggering of platelet aggregation or an inflammatory response may contribute to or promote the development of IE.

scholarly journals A Mutation in the PP2C Phosphatase Gene in a Staphylococcus aureus USA300 Clinical Isolate with Reduced Susceptibility to Vancomycin and Daptomycin

2012 ◽  
Vol 56 (10) ◽  
pp. 5212-5223 ◽  
Author(s):  
Karla D. Passalacqua ◽  
Sarah W. Satola ◽  
Emily K. Crispell ◽  
Timothy D. Read
Keyword(s):  
Staphylococcus Aureus ◽  
Metal Binding ◽  
De Novo ◽  
Surface Protein ◽  
Complex Nature ◽  
Insertion Mutation ◽  
Content Type ◽  
Metal Binding Domain ◽  
Multiple Routes

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains with reduced susceptibility to vancomycin (MIC of 4 to 8 μg/ml) are referred to as vancomycin-intermediateS. aureus(VISA). In this study, we characterized two isogenic USA300S. aureusisolates collected sequentially from a single patient with endocarditis where theS. aureusisolate changed from being susceptible to vancomycin (VSSA) (1 μg/ml) to VISA (8 μg/ml). In addition, the VISA isolate lost beta-lactamase activity and showed increased resistance to daptomycin and linezolid. The two strains did not differ in growth rate, but the VISA isolate had a thickened cell wall and was less autolytic. Transcriptome sequencing (RNA-seq) analysis comparing the two isolates grown to late exponential phase showed significant differences in transcription of cell surface protein genes (spa, SBI [second immunoglobulin-binding protein ofS. aureus], and fibrinogen-binding proteins), regulatory genes (agrBCA, RNAIII,sarT, andsaeRS), and others. Using whole-genome shotgun resequencing, we identified 6 insertion/deletion mutations between the VSSA and VISA isolates. A protein phosphatase 2C (PP2C) family phosphatase had a 6-bp (nonframeshift) insertion mutation in a highly conserved metal binding domain. Complementation of the clinical VISA isolate with a wild-type copy of the PP2C gene reduced the vancomycin and daptomycin MICs and increased autolytic activity, suggesting that this gene contributed to the reduced vancomycin susceptibility phenotype acquiredin vivo. Creation ofde novomutants from the VSSA strain resulted in different mutations, demonstrating that reduced susceptibility to vancomycin in USA300 strains can occur via multiple routes, highlighting the complex nature of the VISA phenotype.

scholarly journals Characterization of the Streptococcus mutans SMU.1703c-SMU.1702c Operon Reveals Its Role in Riboflavin Import and Response to Acid Stress

2020 ◽  
Vol 203 (2) ◽  
pp. e00293-20
Author(s):  
Matthew E. Turner ◽  
Khanh Huynh ◽  
Ronan K. Carroll ◽  
Sang-Joon Ahn ◽  
Kelly C. Rice
Keyword(s):  
Oral Cavity ◽  
Streptococcus Mutans ◽  
Tooth Enamel ◽  
Acid Stress ◽  
Oral Bacteria ◽  
Flavin Mononucleotide ◽  
Dependent Manner ◽  
Oral Streptococci ◽  
Uncharacterized Protein ◽  
Content Type

ABSTRACTStreptococcus mutans utilizes numerous metabolite transporters to obtain essential nutrients in the “feast or famine” environment of the human mouth. S. mutans and most other streptococci are considered auxotrophic for several essential vitamins including riboflavin (vitamin B2), which is used to generate key cofactors and to perform numerous cellular redox reactions. Despite the well-known contributions of this vitamin to central metabolism, little is known about how S. mutans obtains and metabolizes B2. The uncharacterized protein SMU.1703c displays high sequence homology to the riboflavin transporter RibU. Deletion of SMU.1703c hindered S. mutans growth in complex and defined medium in the absence of saturating levels of exogenous riboflavin, whereas deletion of cotranscribed SMU.1702c alone had no apparent effect on growth. Expression of SMU.1703c in a Bacillus subtilis riboflavin auxotroph functionally complemented growth in nonsaturating riboflavin conditions. S. mutans was also able to grow on flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) in an SMU.1703c-dependent manner. Deletion of SMU.1703c and/or SMU.1702c impacted S. mutans acid stress tolerance, as all mutants showed improved growth at pH 5.5 compared to that of the wild type when medium was supplemented with saturating riboflavin. Cooccurrence of SMU.1703c and SMU.1702c, a hypothetical PAP2 family acid phosphatase gene, appears unique to the streptococci and may suggest a connection of SMU.1702c to the acquisition or metabolism of flavins within this genus. Identification of SMU.1703c as a RibU-like riboflavin transporter furthers our understanding of how S. mutans acquires essential micronutrients within the oral cavity and how this pathogen successfully competes within nutrient-starved oral biofilms.IMPORTANCE Dental caries form when acid produced by oral bacteria erodes tooth enamel. This process is driven by the fermentative metabolism of cariogenic bacteria, most notably Streptococcus mutans. Nutrient acquisition is key in the competitive oral cavity, and many organisms have evolved various strategies to procure carbon sources or necessary biomolecules. B vitamins, such as riboflavin, which many oral streptococci must scavenge from the oral environment, are necessary for survival within the competitive oral cavity. However, the primary mechanism and proteins involved in this process remain uncharacterized. This study is important because it identifies a key step in S. mutans riboflavin acquisition and cofactor generation, which may enable the development of novel anticaries treatment strategies via selective targeting of metabolite transporters.

scholarly journals The Antibacterial Activity of LL-37 against Treponema denticola Is Dentilisin Protease Independent and Facilitated by the Major Outer Sheath Protein Virulence Factor

2011 ◽  
Vol 80 (3) ◽  
pp. 1107-1114 ◽  
Author(s):  
Graciela Rosen ◽  
Michael N. Sela ◽  
Gilad Bachrach
Keyword(s):  
Periodontal Disease ◽  
Host Defense ◽  
Surface Protein ◽  
Human Saliva ◽  
Treponema Denticola ◽  
Host Defense Peptides ◽  
Content Type ◽  
Outer Sheath ◽  
Major Surface

Host defense peptides are innate immune effectors that possess both bactericidal activities and immunomodulatory functions. Deficiency in the human host defense peptide LL-37 has previously been correlated with severe periodontal disease.Treponema denticolais an oral anaerobic spirochete closely associated with the pathogenesis of periodontal disease. TheT. denticolamajor surface protein (MSP), involved in adhesion and cytotoxicity, and the dentilisin serine protease are key virulence factors of this organism. In this study, we examined the interactions between LL-37 andT. denticola. The threeT. denticolastrains tested were susceptible to LL-37. Dentilisin was found to inactivate LL-37 by cleaving it at the Lys, Phe, Gln, and Val residues. However, dentilisin deletion did not increase the susceptibility ofT. denticolato LL-37. Furthermore, dentilisin activity was found to be inhibited by human saliva. In contrast, a deficiency of theT. denticolaMSP increased resistance to LL-37. The MSP-deficient mutant bound less fluorescently labeled LL-37 than the wild-type strain. MSP demonstrated specific, dose-dependent LL-37 binding. In conclusion, though capable of LL-37 inactivation, dentilisin does not protectT. denticolafrom LL-37. Rather, the rapid, MSP-mediated binding of LL-37 to the treponemal outer sheath precedes cleavage by dentilisin. Moreover,in vivo, saliva inhibits dentilisin, thus preventing LL-37 restriction and ensuring its bactericidal and immunoregulatory activities.

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