scholarly journals MODERN APPROACHES TO ANTIVIRULENT THERAPY OF DISEASES ASSOCIATED WITH STAPHYLOCOCCUS AUREUS

2019 ◽  
Vol 23 (3-4) ◽  
pp. 26-31
Author(s):  
T.O. Kryuchko ◽  
O.Ya. Tkachenko ◽  
N.V. Kuzmenko ◽  
I.N. Nesina ◽  
S.M. Tanianska ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Effective Means ◽  
Bacterial Pathogen ◽  
Cross Reactivity ◽  
Main Function ◽  
Virulence Proteins ◽  
New Antibiotics ◽  
Active Research

Staphylococcus aureus is a universal bacterial pathogen, which is able to develop the resistance to new antibiotics, by means of virulence factors, whose main function is the spread of diseases by inhibiting the immune factors of host defense. Its wide spread at in-patient departments and also the presence of clinical probationary wards Staphylococcus aureus, resistant to methicillin at out-patient departments, deprive the doctors of effective means for control of the infection. Complications caused by MRSA lead to hospitalization and indices of lethality. The aim of the paper is to analyze the main factors of S. аureus virulence and ways the of its interaction as a result of etiological and pathogenetic treatment. Complexity of treatment of bacterial infections is determined by alternative ways of prevention and treatment of diseases to which bacteria are not able to develop resistance. Along with general mechanisms that form antibiotic resistance, S. aureus produces many individual virulence factors that model the immune response, affecting the survival of the microorganism. The virulence factors produced by S. aureus are diverse and have the ability not only to cause cell lysis, but also to stimulate tissue rejection and destruction. It is important to determine that many specific factors of virulence caused by S. aureus, have ability to change both congenital and adaptive immune reactions including inhibition of complement activation, neutrophils neutralization, phagocytes inhibition. Strategies for inhibiting virulence factors can range from using small inhibitor molecules or full-fledged antibodies to creating toxoids and virulence proteins. Great interest is focused upon those inhibitors that have cross-reactivity with respect to multiple virulence factors, as well as inhibitors, the main target of which is a global regulator with multi-purpose activity, for example, agr operon. Active research into the specific alternative antivirulent treatments for severe diseases caused by S. aureus can potentially settle a number of problems and difficulties of post-antibiotic era.

scholarly journals Design and Synthesis of Small Molecules as Potent Staphylococcus aureus Sortase A Inhibitors

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 706
Author(s):  
Min Woo Ha ◽  
Sung Wook Yi ◽  
Seung-Mann Paek
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Resistant Bacteria ◽  
Sortase A ◽  
Bacterial Survival ◽  
Promising Alternative ◽  
Design And Synthesis ◽  
New Antibiotics ◽  
Pathogenic Action ◽  
New Generation

The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in virulence and its nonessentiality in bacterial survival, sortase A has been considered as a great target for new antibiotics. Sortase A inhibitors have emerged as promising alternative antivirulence agents against bacteria. Herein, the structural and preparative aspects of some small synthetic organic compounds that block the pathogenic action of sortase A have been described.

scholarly journals Rapid Visualization and Detection of Staphylococcus Aureus Based on Loop-Mediated Isothermal Amplification

2021 ◽  
Author(s):  
Chuan Wu ◽  
Yuanyuan Zeng ◽  
Yang He
Keyword(s):  
Staphylococcus Aureus ◽  
Limit Of Detection ◽  
Reaction System ◽  
Bacterial Pathogen ◽  
Lamp Assay ◽  
Cross Reactivity ◽  
Isothermal Amplification ◽  
Diagnostic Efficacy ◽  
Diverse Range ◽  
Loop Mediated Isothermal Amplification

Abstract Staphylococcus aureus is a common clinical bacterial pathogen that can cause a diverse range of infections. The establishment of a rapid and reliable assay for the early diagnosis and detection of S. aureus is of great significance. In this study, we developed a closed-tube loop-mediated isothermal amplification (LAMP) assay for the visual detection of S. aureus using the colorimetric indicator hydroxy naphthol blue (HNB). The LAMP reaction was optimized by adjusting the amplification temperature, the concentrations of Mg2+, dNTP, and HNB, and the incubation time. In the optimized reaction system, the specificity of LAMP for S. aureus was 100%. The results established that this method accurately identified S. aureus, with no cross-reactivity with 16 non-S. aureus strains. The limit of detection (LOD) of LAMP was 8 copies/reaction of purified plasmid DNA or 400 colony-forming units/reaction of S. aureus. Compared with conventional PCR, LAMP lowered the LOD by 10-fold. Finally, 220 clinically isolated strains of S. aureus and 149 non-S. aureus strains were used to evaluate the diagnostic efficacy of LAMP. The findings indicated that LAMP is a reliable test for S. aureus and could be a promising tool for the rapid diagnosis of S. aureus infections.

scholarly journals Metabolites alleviate staphylococcal bloodstream infection in a NO-dependent manner via arginase inhibition

2020 ◽  
Author(s):  
Rui Pang ◽  
Yu-bin Su ◽  
Hua Zhou ◽  
Xinhai Chen
Keyword(s):  
Innate Immunity ◽  
Bloodstream Infection ◽  
Bacterial Infections ◽  
Bacterial Pathogen ◽  
Bloodstream Infections ◽  
Resistance Mechanisms ◽  
Dependent Manner ◽  
Metabolomics Study ◽  
New Antibiotics ◽  
Powerful Strategy

AbstractStaphylococcus aureus is a notorious bacterial pathogen that often causes soft tissue and bloodstream infections and invariably garners resistance mechanisms against new antibiotics. Host innate immunity modulated by metabolites has been proved as a powerful strategy against bacterial infections. However, few studies focus on the application of this strategy against S. aureus infection. Here, we identified four metabolite biomarkers, L-proline, L-isoleucine, L-leucine, and L-valine (PILV), by a metabolomics study. In animal models of S. aureus bloodstream infection, exogenous administration of each metabolite or PILV shows an anti-infective effect, while PILV treatment has higher protection than individual metabolite treatment. Each metabolite targets nitric oxide (NO) to kill S. aureus via arginase inhibition, and PILV exhibits additive inhibition of arginase activity that causes further killing. This suppression also contributes to the metabolite-mediated phagocytic killing of S. aureus in human blood. Our finding demonstrates the metabolite-mediated innate immunity as a therapeutic intervention for S. aureus infection.

scholarly journals Nusbiarylins Inhibit Transcription and Target Virulence Factors in Bacterial Pathogen Staphylococcus aureus

2020 ◽  
Vol 21 (16) ◽  
pp. 5772
Author(s):  
Adrian Jun Chu ◽  
Yangyi Qiu ◽  
Rachel Harper ◽  
Lin Lin ◽  
Cong Ma ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Antimicrobial Agents ◽  
Bacterial Pathogen ◽  
Cellular Respiration ◽  
Regulatory Pathways ◽  
Protein Levels ◽  
Transcription Inhibitors ◽  
Bacterial Transcription

The emergence of multidrug resistance in the clinically significant pathogen Staphylococcus aureus is a global health burden, compounded by a diminishing drug development pipeline, and a lack of approved novel antimicrobials. Our previously reported first-in-class bacterial transcription inhibitors “nusbiarylins” presented a promising prospect towards the discovery of novel antimicrobial agents with a novel mechanism. Here we investigated and characterised the lead nusbiarylin compound, MC4, and several of its chemical derivatives in both methicillin-resistant S. aureus (MRSA) and the S. aureus type strains, demonstrating their capacity for the arrest of growth and cellular respiration, impairment of RNA and intracellular protein levels at subinhibitory concentrations. In some instances, derivatives of MC4 were also shown to attenuate the production of staphylococcal virulence factors in vitro, such as the exoproteins α-toxin and Panton–Valentine Leukocidin (PVL). Trends observed from quantitative PCR assays suggested that nusbiarylins elicited these effects possibly by acting via but not limited to the modulation of global regulatory pathways, such as the agr regulon, which coordinates the expression of S. aureus genes associated with virulence. Our findings encourage the continued development of more potent compounds within this novel family of bacterial transcription inhibitors.

"Review Article Pathogenicity and virulence factors in Staphylococcus aureus

2021 ◽  
Vol 8 (1) ◽  
pp. 109-119
Author(s):  
Shaimaa M. S. Zainulabdeen ◽  
Adian A. Dakl
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Marrow ◽  
Virulence Factors ◽  
Immune Cells ◽  
Review Article ◽  
Necrotic Bone ◽  
Virulence Proteins ◽  
Hospital Acquired Infections ◽  
Living Bone ◽  
Hospital Acquired

"Staphylococcus aureus is a pathogen that resides in the skin and nasal membranes and can cause a broad spectrum of hospital-acquired infections. These diseases are becoming more common, and treating them has become much more complicated. The pathogen’s capacity to secret a variety of host-damaging virulence factors contributes to its pathogenicity. S. aureus destroys and supersedes immune cells throughout infection via toxins and virulence proteins, yielding non-neutralizing infective antibodies which already impede adaptive immunity. S. aureus has different biofilm-forming mechanisms on devices, necrotic bone tissue, bone marrow, and finally within the osteocyte lacuno-canicular networks of living bone (OLCN).This review focuses on gaining a better understanding of S. aureus toxin-based pathogenesis and its effects on infectious diseases.

scholarly journals Requirement of Signal Peptidase ComC and Thiol-Disulfide Oxidoreductase DsbA for Optimal Cell Surface Display of Pseudopilin ComGC in Staphylococcus aureus

2012 ◽  
Vol 78 (19) ◽  
pp. 7124-7127 ◽  
Author(s):  
Magdalena M. van der Kooi-Pol ◽  
Ewoud Reilman ◽  
Mark J. J. B. Sibbald ◽  
Yanka K. Veenstra-Kyuchukova ◽  
Thijs R. H. M. Kouwen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Surface ◽  
Virulence Factors ◽  
Surface Display ◽  
Bacterial Pathogen ◽  
Cell Surface Display ◽  
Signal Peptidase ◽  
Gram Positive ◽  
Content Type ◽  
Disulfide Oxidoreductase

ABSTRACTStaphylococcus aureusis an important Gram-positive bacterial pathogen producing many secreted and cell surface-localized virulence factors. Here we report that the staphylococcal thiol-disulfide oxidoreductase DsbA is essential for stable biogenesis of the ComGC pseudopilin. The signal peptidase ComC is indispensable for ComGC maturation and optimal cell surface exposure.

scholarly journals Antivirulence effects of pomegranate peel extracts on most common urinary tract infection pathogens in pregnant women

2016 ◽  
Vol 1 (4) ◽  
pp. 7 ◽  
Author(s):  
Wafaa Sadeq Al-Wazni ◽  
Bashair Sami Hadi
Keyword(s):  
Staphylococcus Aureus ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogen ◽  
Pomegranate Peel ◽  
Alcohol Extract ◽  
Inhibition Zones

Objective This study includes the investigation of antibacterial and antivirulence activities of three types of pomegranate peel extracts andthen determines the interaction between the extracts and antibiotic in vitro.Methods The ability of most common isolated bacteria from urinary tract infection (UTI) to produce different virulence factors were testedand the effect of plant extracts on virulence factors were determined; in addition the correlation between extracts and antibiotics wereevaluated by using fractional inhibitory concentrations.Results The inhibition zones diameters of the pomegranate peel extracts against most common isolated bacteria (Staphylococcus aureus andEscherichia coli) increase significantly with increase in concentrations. There is no effect of the extracts on the ability of studied bacteria toproduce hemolysin and protease enzymes, while both studied bacteria lost its ability to produce β-lactamase enzyme after treating with MIC.In addition, extracts were affected largely on adherence activity and biofilm forming ability of tested bacteria. The results found that thepomegranate peel extracts effect alone against pathogenic bacteria was good than they interacted with antibiotics, in most of the results.Conclusion The alcohol extract was the best solvent in its effects on bacterial pathogen and its effect was largely on the ability of the studiedbacteria to form biofilm and adhesion on the epithelial cell. The pomegranate peel extracts were high synergism with some antibioticsagainst pathogenic bacteria.

The antibacterial activity of 1,2,3-triazole- and 1,2,4-triazole-containing hybrids against Staphylococcus aureus: An updated review (2020-present)

2021 ◽  
Vol 21 ◽  
Author(s):  
Jie Li ◽  
Junwei Zhang
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Broad Spectrum ◽  
Bacterial Infections ◽  
Bacterial Pathogen ◽  
Temperature Sensitive ◽  
Protein Z ◽  
Topoisomerase Iv ◽  
Antibiotic Resistant ◽  
Clinically Significant

: Staphylococcus aureus (S. aureus), a prominent, highly contagious nosocomial and community-acquired bacterial pathogen, can cause a broad spectrum of diseases. Antibiotic-resistant S. aureus strains, which pose potential causes of morbidity and mortality, have continuously emerged in recent years, calling for novel anti-S. aureus agents. 1,2,3-Triazole and 1,2,4-triazole, the bioisostere of amides, esters, and carboxylic acids, are potent inhibitors of DNA gyrase, topoisomerase IV, efflux pumps, filamentous temperature-sensitive protein Z, and penicillin-binding protein. In particular, 1,2,3-triazole- and 1,2,4-triazole-containing hybrids have the potential to exert dual or multiple antibacterial mechanisms of action. Moreover, 1,2,3-triazole-cephalosporin hybrid cefatrizine, 1,2,3-triazole-oxazolidinone hybrid radezolid, and 1,2,4-triazolo[1,5-a]pyrimidine hybrid essramycin, have already been used in clinical practice to treat bacterial infections. Hence, 1,2,3-triazole- and 1,2,4-triazole-containing hybrids possess promising broad-spectrum antibacterial activity against diverse clinically significant organisms, including drug-resistant forms. This review is an update on the latest development of 1,2,3-triazole- and 1,2,4-triazole-containing hybrids with anti-S. aureus activity, covering articles published between January 2020 and July 2021.

scholarly journals Staphylococcus aureus Responds to the Central Metabolite Pyruvate To Regulate Virulence

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Lamia Harper ◽  
Divya Balasubramanian ◽  
Elizabeth A. Ohneck ◽  
William E. Sause ◽  
Jessica Chapman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Virulence Factors ◽  
Regulatory Networks ◽  
Metabolic Flux ◽  
Bacterial Pathogen ◽  
Strong Relationship ◽  
Global Changes ◽  
Human Pathogens ◽  
Environmental Signals

ABSTRACTStaphylococcus aureusis a versatile bacterial pathogen that can cause significant disease burden and mortality. Like other pathogens,S. aureusmust adapt to its environment to produce virulence factors to survive the immune responses evoked by infection. Despite the importance of environmental signals forS. aureuspathogenicity, only a limited number of these signals have been investigated in detail for their ability to modulate virulence. Here we show that pyruvate, a central metabolite, causes alterations in the overall metabolic flux ofS. aureusand enhances its pathogenicity. We demonstrate that pyruvate induces the production of virulence factors such as the pore-forming leucocidins and that this induction results in increased virulence of community-acquired methicillin-resistantS. aureus(CA-MRSA) clone USA300. Specifically, we show that an efficient “pyruvate response” requires the activation ofS. aureusmaster regulators AgrAC and SaeRS as well as the ArlRS two-component system. Altogether, our report further establishes a strong relationship between metabolism and virulence and identifies pyruvate as a novel regulatory signal for the coordination of theS. aureusvirulon through intricate regulatory networks.IMPORTANCEDelineation of the influence of host-derived small molecules on the makeup of human pathogens is a growing field in understanding host-pathogen interactions.S. aureusis a prominent pathogen that colonizes up to one-third of the human population and can cause serious infections that result in mortality in ~15% of cases. Here, we show that pyruvate, a key nutrient and central metabolite, causes global changes to the metabolic flux ofS. aureusand activates regulatory networks that allow significant increases in the production of leucocidins. These and other virulence factors are critical forS. aureusto infect diverse host niches, initiate infections, and effectively subvert host immune responses. Understanding how environmental signals, particularly ones that are essential to and prominent in the human host, affect virulence will allow us to better understand pathogenicity and consider more-targeted approaches to tackling the currentS. aureusepidemic.

Garlic Extract (Allium sativum L.) Effectively Inhibits Staphylococcus aureus and Escherichia coli by Invitro Test

2020 ◽  
Vol 2 (2) ◽  
pp. 61-68
Author(s):  
Agnina Listya Anggraini ◽  
Ratih Dewi Dwiyanti ◽  
Anny Thuraidah
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Allium Sativum ◽  
Antibacterial Properties ◽  
Herbal Medicines ◽  
Garlic Extract ◽  
Dilution Method ◽  
Initial Stage

Infection is a disease caused by the presence of pathogenic microbes, including Staphylococcus aureus and Escherichia coli. Garlic (Allium sativum L.) has chemical contents such as allicin, alkaloids, flavonoids, saponins, tannins, and steroids, which can function as an antibacterial against Staphylococcus aureus and Escherichia coli. This study aims to determine the antibacterial properties of garlic extract powder against Staphylococcus aureus and Escherichia coli. This research is the initial stage of the development of herbal medicines to treat Staphylococcus aureus and Escherichia coli infections. The antibacterial activity test was carried out by the liquid dilution method. The concentrations used were 30 mg/mL, 40 mg/mL, 50 mg/mL, 60 mg/mL and 70 mg/mL. The results showed that the Minimum Inhibitory Concentration (MIC) against Staphylococcus aureus and Escherichia coli was 40 mg/mL and 50 mg / mL. Minimum Bactericidal Concentration (MBC) results for Staphylococcus aureus and Escherichia coli are 50 mg/mL and 70 mg/mL. Based on the Simple Linear Regression test, the R2 value of Staphylococcus aureus and Escherichia coli is 0.545 and 0.785, so it can be concluded that there is an effect of garlic extract powder on the growth of Staphylococcus aureus and Escherichia coli by 54.5% and 78.5%. Garlic (Allium sativum L.) extract powder has potential as herbal medicine against bacterial infections but requires further research to determine its effect in vivo.

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