Molecular Mechanisms of Adhesion of Staphylococcus aureus to Cardiac Surfaces and Vegetations

1997 ◽  
pp. 138-144
Author(s):  
C. M. Johnson
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Mechanisms ◽  
Mechanisms Of Adhesion

scholarly journals Human urine alters methicillin-resistant Staphylococcus aureus virulence and transcriptome

2021 ◽  
Author(s):  
Santosh Paudel ◽  
Kamal Bagale ◽  
Swapnil Patel ◽  
Nicholas J. Kooyers ◽  
Ritwij Kulkarni
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Human Urine ◽  
Molecular Mechanisms ◽  
Methicillin Resistant ◽  
Life Threatening ◽  
Tract Infections

Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections (UTI), especially in catheterized individuals. Despite being rare, MRSA UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. To delineate the molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus clinical isolates, including two MRSA strains to human urine for 2h and analyzed virulence characteristics and changes in gene expression. The in vitro virulence assays showed that human urine rapidly alters adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep RBCs, and surface hydrophobicity in a staphylococcal strain-specific manner. In addition, RNA-Seq analysis of uropathogenic strain MRSA-1369 revealed that 2h-long exposure to human urine alters MRSA transcriptome, by modifying expression of genes encoding enzymes catalyzing metabolic pathways, virulence factors, and transcriptional regulators. In summary, our results provide important insights into how human urine specifically and rapidly alters MRSA physiology and facilitates MRSA survival in the nutrient-limiting and hostile urinary microenvironment. Importance: Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. In this report, we describe how exposure to human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA in acclimating to the nutrient-limiting, immunologically hostile conditions within the urinary tract leading to MRSA-UTI.

scholarly journals Human Defensins: A Novel Approach in the Fight against Skin Colonizing Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 198 ◽  
Author(s):  
Olga Scudiero ◽  
Mariarita Brancaccio ◽  
Cristina Mennitti ◽  
Sonia Laneri ◽  
Barbara Lombardo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Innate Immunity ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Interleukin 1 ◽  
Interleukin 17 ◽  
Skin Infections ◽  
Skin Disorders ◽  
Novel Approach ◽  
Pharmacological Potential

Staphylococcus aureus is a microorganism capable of causing numerous diseases of the human skin. The incidence of S. aureus skin infections reflects the conflict between the host skin′s immune defenses and the S. aureus’ virulence elements. Antimicrobial peptides (AMPs) are small protein molecules involved in numerous biological activities, playing a very important role in the innate immunity. They constitute the defense of the host′s skin, which prevents harmful microorganisms from entering the epithelial barrier, including S. aureus. However, S. aureus uses ambiguous mechanisms against host defenses by promoting colonization and skin infections. Our review aims to provide a reference collection on host-pathogen interactions in skin disorders, including S. aureus infections and its resistance to methicillin (MRSA). In addition to these, we discuss the involvement of defensins and other innate immunity mediators (i.e., toll receptors, interleukin-1, and interleukin-17), involved in the defense of the host against the skin disorders caused by S. aureus, and then focus on the evasion mechanisms developed by the pathogenic microorganism under analysis. This review provides the “state of the art” on molecular mechanisms underlying S. aureus skin infection and the pharmacological potential of AMPs as a new therapeutic strategy, in order to define alternative directions in the fight against cutaneous disease.

scholarly journals Exotoxins of Staphylococcus aureus

2000 ◽  
Vol 13 (1) ◽  
pp. 16-34 ◽  
Author(s):  
Martin M. Dinges ◽  
Paul M. Orwin ◽  
Patrick M. Schlievert
Keyword(s):  
Staphylococcus Aureus ◽  
Toxic Shock Syndrome ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Food Poisoning ◽  
Structure And Function ◽  
Toxic Shock ◽  
The Family ◽  
Toxic Shock Syndrome Toxin ◽  
And Function

SUMMARY This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens (PTSAgs) and hemolysins. The molecular basis of PTSAg toxicity is presented in the context of two diseases known to be caused by these exotoxins: toxic shock syndrome and staphylococcal food poisoning. The family of staphylococcal PTSAgs presently includes toxic shock syndrome toxin-1 (TSST-1) and most of the staphylococcal enterotoxins (SEs) (SEA, SEB, SEC, SED, SEE, SEG, and SEH). As the name implies, the PTSAgs are multifunctional proteins that invariably exhibit lethal activity, pyrogenicity, superantigenicity, and the capacity to induce lethal hypersensitivity to endotoxin. Other properties exhibited by one or more staphylococcal PTSAgs include emetic activity (SEs) and penetration across mucosal barriers (TSST-1). A detailed review of the molecular mechanisms underlying the toxicity of the staphylococcal hemolysins is also presented.

scholarly journals Advanced Resistance Studies Identify Two Discrete Mechanisms in Staphylococcus aureus to Overcome Antibacterial Compounds that Target Biotin Protein Ligase

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 165 ◽  
Author(s):  
Andrew J. Hayes ◽  
Jiulia Satiaputra ◽  
Louise M. Sternicki ◽  
Ashleigh S. Paparella ◽  
Zikai Feng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Transcriptional Repression ◽  
Molecular Mechanisms ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Resistance Rate ◽  
Biotin Protein Ligase ◽  
Essential Enzyme

Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically important methicillin-resistant Staphylococcus aureus (S. aureus). In S. aureus, BPL is a bifunctional protein responsible for enzymatic biotinylation of two biotin-dependent enzymes, as well as serving as a transcriptional repressor that controls biotin synthesis and import. In this report, we investigate the mechanisms of action and resistance for a potent anti-BPL, an antibacterial compound, biotinyl-acylsulfamide adenosine (BASA). We show that BASA acts by both inhibiting the enzymatic activity of BPL in vitro, as well as functioning as a transcription co-repressor. A low spontaneous resistance rate was measured for the compound (<10−9) and whole-genome sequencing of strains evolved during serial passaging in the presence of BASA identified two discrete resistance mechanisms. In the first, deletion of the biotin-dependent enzyme pyruvate carboxylase is proposed to prioritize the utilization of bioavailable biotin for the essential enzyme acetyl-CoA carboxylase. In the second, a D200E missense mutation in BPL reduced DNA binding in vitro and transcriptional repression in vivo. We propose that this second resistance mechanism promotes bioavailability of biotin by derepressing its synthesis and import, such that free biotin may outcompete the inhibitor for binding BPL. This study provides new insights into the molecular mechanisms governing antibacterial activity and resistance of BPL inhibitors in S. aureus.

scholarly journals Molecular mechanisms of thioridazine resistance in Staphylococcus aureus

PLoS ONE ◽  
2018 ◽  
Vol 13 (8) ◽  
pp. e0201767 ◽  
Author(s):  
Claes Søndergaard Wassmann ◽  
Lars Christian Lund ◽  
Mette Thorsing ◽  
Sabrina Prehn Lauritzen ◽  
Hans Jørn Kolmos ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Mechanisms

scholarly journals How Microbes Use Force To Control Adhesion

2020 ◽  
Vol 202 (12) ◽  
Author(s):  
Albertus Viljoen ◽  
Johann Mignolet ◽  
Felipe Viela ◽  
Marion Mathelié-Guinlet ◽  
Yves F. Dufrêne
Keyword(s):  
Single Molecule ◽  
Molecular Mechanisms ◽  
Flow Chamber ◽  
Microbial Adhesion ◽  
Single Molecule Level ◽  
Force Microscopy ◽  
Atomic Force ◽  
Adhesive Interactions ◽  
And Function ◽  
Mechanisms Of Adhesion

ABSTRACT Microbial adhesion and biofilm formation are usually studied using molecular and cellular biology assays, optical and electron microscopy, or laminar flow chamber experiments. Today, atomic force microscopy (AFM) represents a valuable addition to these approaches, enabling the measurement of forces involved in microbial adhesion at the single-molecule level. In this minireview, we discuss recent discoveries made applying state-of-the-art AFM techniques to microbial specimens in order to understand the strength and dynamics of adhesive interactions. These studies shed new light on the molecular mechanisms of adhesion and demonstrate an intimate relationship between force and function in microbial adhesins.

scholarly journals Staphylococcus aureus α-Toxin Induces Inflammatory Cytokines via Lysosomal Acid Sphingomyelinase and Ceramides

2017 ◽  
Vol 43 (6) ◽  
pp. 2170-2184 ◽  
Author(s):  
Jie Ma ◽  
Erich Gulbins ◽  
Michael J. Edwards ◽  
Charles C. Caldwell ◽  
Martin Fraunholz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Confocal Microscopy ◽  
Inflammatory Cytokines ◽  
Cathepsin B ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Clinical Problem ◽  
Acid Sphingomyelinase ◽  
Tnf Α ◽  
Factor Α

Background/Aims: Staphylococcus aureus (S. aureus) infections are a major clinical problem and range from mild skin and soft-tissue infections to severe and even lethal infections such as pneumonia, endocarditis, sepsis, osteomyelitis, and toxic shock syndrome. Toxins that are released from S. aureus mediate many of these effects. Here, we aimed to identify molecular mechanisms how α-toxin, a major S. aureus toxin, induces inflammation. Methods: Macrophages were isolated from the bone marrow of wildtype and acid sphingomyelinase-deficient mice, stimulated with S. aureus α-toxin and activation of the acid sphingomyelinase was quantified. The subcellular formation of ceramides was determined by confocal microscopy. Release of cathepsins from lysosomes, activation of inflammasome proteins and formation of Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) were analyzed by western blotting, confocal microscopy and ELISA. Results: We demonstrate that S. aureus α-toxin activates the acid sphingomyelinase in ex vivo macrophages and triggers a release of ceramides. Ceramides induced by S. aureus α-toxin localize to lysosomes and mediate a release of cathepsin B and D from lysosomes into the cytoplasm. Cytosolic cathepsin B forms a complex with Nlrc4. Treatment of macrophages with α-toxin induces the formation of IL-1β and TNF-α. These events are reduced or abrogated, respectively, in cells lacking the acid sphingomyelinase and upon treatment of macrophages with amitriptyline, a functional inhibitor of acid sphingomyelinase. Pharmacological inhibition of cathepsin B prevented activation of the inflammasome measured as release of IL-1β, while the formation of TNF-α was independent of cathepsin B. Conclusion: We demonstrate a novel mechanism how bacterial toxins activate the inflammasome and mediate the formation and release of cytokines: S. aureus α-toxin triggers an activation of the acid sphingomyelinase and a release of ceramides resulting in the release of lysosomal cathepsin B and formation of pro-inflammatory cytokines.

scholarly journals Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin

2016 ◽  
Vol 60 (10) ◽  
pp. 5957-5967 ◽  
Author(s):  
Katrin Schilcher ◽  
Federica Andreoni ◽  
Vanina Dengler Haunreiter ◽  
Kati Seidl ◽  
Barbara Hasse ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Treatment ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Extracellular Dna ◽  
Content Type ◽  
Transcriptional Stress ◽  
Sigma Factor B ◽  
Subinhibitory Concentrations ◽  
Biofilm Matrix

ABSTRACTStaphylococcus aureusbiofilms are extremely difficult to treat. They provide a protected niche for the bacteria, rendering them highly recalcitrant toward host defenses as well as antibiotic treatment. Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response inS. aureusvia the alternative sigma factor B (σB) and upregulated the expression of the major biofilm-associated genesatlA,lrgA,agrA, thepsmgenes,fnbA, andfnbB. Our data suggest that subinhibitory concentrations of clindamycin alter the ability ofS. aureusto form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associatedS. aureusinfections.

scholarly journals Identification of Point Mutations in Clinical Staphylococcus aureus Strains That Produce Small-Colony Variants Auxotrophic for Menadione

2014 ◽  
Vol 82 (4) ◽  
pp. 1600-1605 ◽  
Author(s):  
Melissa A. Dean ◽  
Randall J. Olsen ◽  
S. Wesley Long ◽  
Adriana E. Rosato ◽  
James M. Musser
Keyword(s):  
Staphylococcus Aureus ◽  
Pathway Analysis ◽  
Molecular Mechanisms ◽  
Point Mutations ◽  
Biosynthesis Pathway ◽  
Wild Type ◽  
Small Colony Variants ◽  
Content Type ◽  
Genes Encoding ◽  
Small Colony

ABSTRACTStaphylococcus aureussmall-colony variants (SCVs) are implicated in chronic and relapsing infections that are difficult to diagnose and treat. Despite many years of study, the underlying molecular mechanisms and virulence effect of the small-colony phenotype remain incompletely understood. We sequenced the genomes of fiveS. aureusSCV strains recovered from human patients and discovered previously unidentified nonsynonymous point mutations in three genes encoding proteins in the menadione biosynthesis pathway. Analysis of genetic revertants and complementation with wild-type alleles confirmed that these mutations caused the SCV phenotype and decreased virulence for mice.

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