Exploring Staphylococcus aureus Virulence Factors; Special Emphasis on Staphyloxanthin

2021 ◽  
Author(s):  
Fatma Al-zahraa A. Yehia ◽  
Nehal Yousef ◽  
Momen Askoura
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors

scholarly journals 1202. Subinhibitory Concentrations of Omadacycline Inhibit Staphylococcus aureus Hemolytic Activity in Vitro

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S622-S623
Author(s):  
Alisa W Serio ◽  
S Ken Tanaka ◽  
Kelly Wright ◽  
Lynne Garrity-Ryan
Keyword(s):  
Staphylococcus Aureus ◽  
Protein Synthesis ◽  
Virulence Factors ◽  
Hemolytic Activity ◽  
Protein Biosynthesis ◽  
The United States ◽  
Aureus Strain ◽  
Protein Synthesis Inhibitors ◽  
Subinhibitory Concentrations

Abstract Background In animal models of Staphylococcus aureus infection, α-hemolysin has been shown to be a key virulence factor. Treatment of S. aureus with subinhibitory levels of protein synthesis inhibitors can decrease α-hemolysin expression. Omadacycline, a novel aminomethylcycline antibiotic in the tetracycline class of bacterial protein biosynthesis inhibitors, is approved in the United States for treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults. This study was performed to determine the durability of inhibition and effect of subinhibitory concentrations of omadacycline on S. aureus hemolytic activity. Methods All experiments used the methicillin-sensitive S. aureus strain Wood 46 (ATCC 10832), a laboratory strain known to secrete high levels of α-hemolysin. Minimum inhibitory concentrations (MICs) of omadacycline and comparator antibiotics (tetracycline, cephalothin, clindamycin, vancomycin, linezolid) were determined. Growth of S. aureus with all antibiotics was determined and the percentage of hemolysis assayed. “Washout” experiments were performed with omadacycline only. Results S. aureus cultures treated with 1/2 or 1/4 the MIC of omadacycline for 4 hours showed hemolysis units/108 CFU of 47% and 59% of vehicle-treated cultures, respectively (Fig. 1A, 1B). In washout experiments, treatment with as little as 1/4 the MIC of omadacycline for 1 hour decreased the hemolysis units/108 CFU by 60% for 4 hours following removal of the drug (Table 1). Figure 1 Table 1 Conclusion Omadacycline inhibited S. aureus hemolytic activity in vitro at subinhibitory concentrations and inhibition was maintained for ≥ 4 hours after removal of extracellular drug (Fig. 2). The suppression of virulence factors throughout the approved omadacycline dosing interval, in addition to the in vitro potency of omadacycline, may contribute to the efficacy of omadacycline for ABSSSI and CABP due to virulent S. aureus. This finding may apply to other organisms and other virulence factors that require new protein synthesis to establish disease. Figure 2 Disclosures Alisa W. Serio, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) S. Ken Tanaka, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Kelly Wright, PharmD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Lynne Garrity-Ryan, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder)

scholarly journals Phosphorylation of MgrA and Its Effect on Expression of the NorA and NorB Efflux Pumps of Staphylococcus aureus

2010 ◽  
Vol 192 (10) ◽  
pp. 2525-2534 ◽  
Author(s):  
Que Chi Truong-Bolduc ◽  
David C. Hooper
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Virulence Factors ◽  
Double Mutant ◽  
Efflux Pumps ◽  
Efflux Transporters ◽  
Global Regulator ◽  
Binding Assays ◽  
Genes Encoding ◽  
Gel Shift

ABSTRACT MgrA is a global regulator in Staphylococcus aureus that controls the expression of diverse genes encoding virulence factors and multidrug resistance (MDR) efflux transporters. We identified pknB, which encodes the (Ser/Thr) kinase PknB, in the S. aureus genome. PknB was able to autophosphorylate as well as phosphorylate purified MgrA. We demonstrated that rsbU, which encodes a Ser/Thr phosphatase and is involved in the activation of the SigB regulon, was able to dephosphorylate MgrA-P but not PknB-P. Serines 110 and 113 of MgrA were found to be phosphorylated, and Ala substitutions at these positions resulted in reductions in the level of phosphorylation of MgrA. DNA gel shift binding assays using norA and norB promoters showed that MgrA-P was able to bind the norB promoter but not the norA promoter, a pattern which was the reverse of that for unphosphorylated MgrA. The double mutant MgrAS110A-S113A bound to the norA promoter but not the norB promoter. The double mutant led to a 2-fold decrease in norA transcripts and a 2-fold decrease in the MICs of norfloxacin and ciprofloxacin in strain RN6390. Thus, phosphorylation of MgrA results in loss of binding to the norA promoter, but with a gain of the ability to bind the norB promoter. Loss of the ability to phosphorylate MgrA by Ala substitution resulted in increased repression of norA expression and in reductions in susceptibilities to NorA substrates.

New Strategies Targeting Virulence Factors of Staphylococcus aureus and Pseudomonas aeruginosa

2017 ◽  
Vol 38 (03) ◽  
pp. 346-358 ◽  
Author(s):  
Bruno François ◽  
Charles-Edouard Luyt ◽  
C. Stover ◽  
Jeffery Brubaker ◽  
Jean Chastre ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Effective Utilization ◽  
Mechanically Ventilated ◽  
Stage Of Development ◽  
Antivirulence Agents ◽  
Interventional Therapies ◽  
Improve Patient ◽  
New Strategies

AbstractMorbidity, mortality, and economic burden of nosocomial pneumonia caused by Staphylococcus aureus and Pseudomonas aeruginosa remain high in mechanically ventilated and hospitalized patients despite the use of empirical antibiotic therapy or antibiotics against specific classes of pathogens and procedures to reduce nosocomial infections in hospital settings. Newer agents that neutralize or inhibit specific S. aureus or P. aeruginosa virulence factors may eliminate or reduce the risk for developing pneumonia before or during mechanical ventilation and may improve patient outcomes through mechanisms that differ from those of antibiotics. In this article, we review the types, mechanisms of action, potential advantages, and stage of development of antivirulence agents (AVAs) that hold promise as alternative preventive or interventional therapies against S. aureus– and P. aeruginosa–associated nosocomial pneumonias. We also present and discuss challenges to the effective utilization of AVAs separately from or in addition to antibiotics and the design of clinical trials and meaningful study end points.

Virulence Factors of Staphylococcus aureus in the Pathogenesis of Endocarditis A Comparative Study of Clinical Isolates

1998 ◽  
Vol 287 (4) ◽  
pp. 433-447 ◽  
Author(s):  
Shahin Nozohoor ◽  
Anders Heimdahl ◽  
Patricia Colque-Navarro ◽  
Inger Julander ◽  
Bo Söderquist ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Comparative Study ◽  
Virulence Factors ◽  
Clinical Isolates

scholarly journals Molecular characterization of virulence factors in Staphylococcus aureus isolated from bovine subclinical mastitis in central Ethiopia

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Desiye Tesfaye Tegegne ◽  
Gezahegne Mamo ◽  
Hika Waktole ◽  
Yohannes Equar Messele
Keyword(s):  
Staphylococcus Aureus ◽  
Dairy Cows ◽  
Virulence Factors ◽  
Virulence Genes ◽  
Animal Health ◽  
Subclinical Mastitis ◽  
Biochemical Tests ◽  
Milk Samples ◽  
Lactating Dairy Cows ◽  
Genomic Study

Abstract Purpose Staphylococcus aureus (S. aureus) is the most important pathogen involved in bovine mastitis in dairy production. S. aureus produces a spectrum of extracellular protein toxins and virulence factors which are thought to contribute to the pathogenicity of the organism. The aim of this work was to isolate and molecular characterize S. aureus associated with bovine subclinical mastitis in the central part of Ethiopia. Methods A total of 265 lactating dairy cows from various dairy farms in four different geographical locations were screened by the California mastitis test (CMT) for bovine subclinical mastitis. One hundred thirty CMT-positive milk samples were collected and transported to the laboratory. Different biochemical tests and polymerase chain reaction (PCR) were used for the identification of S. aureus isolates. Finally, PCR was performed for molecular detection of virulence genes. Results From a total of 265 lactating dairy cows screened, 49% (n = 130) were positive for bovine subclinical mastitis. One hundred thirty mastitic milk samples were subjected to bacterial culturing, and one hundred (76%) S. aureus isolates were identified based on phenotypic characters. Sixty-eight confirmed S. aureus isolates were obtained using PCR. The confirmed S. aureus isolates were tested for six virulence genes (tsst-1, hlb, eta, sea, clfA, and icaD) using PCR. Of the six virulence genes screened from all the isolates, only two (clfA and eta) were detected in the isolates. Out of 68 isolates, 25% and 22% were possessed the eta and clfA genes, respectively. Conclusion The presence of Staphylococcus aureus having virulence genes (eta and clfA) revealed that mastitis is a major concern nowadays affecting animal health, milk quality, and yield. Further genomic study of these isolates will provide broad new insights on virulence.

Recovery and virulence factors of sublethally injured Staphylococcus aureus after ohmic heating

2021 ◽  
pp. 103899
Author(s):  
Lele Shao ◽  
Yijie Zhao ◽  
Bo Zou ◽  
Xingmin Li ◽  
Ruitong Dai
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Ohmic Heating

scholarly journals Finding of Agr Phase Variants in Staphylococcus aureus

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Vishal Gor ◽  
Aya J. Takemura ◽  
Masami Nishitani ◽  
Masato Higashide ◽  
Veronica Medrano Romero ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Phase Variation ◽  
Accessory Gene ◽  
Content Type ◽  
Accessory Gene Regulator ◽  
Immune Mediated ◽  
A Minor ◽  
First Time ◽  
Phase Variants

ABSTRACT Staphylococcus aureus is an important human pathogen whose success is largely attributed to its vast arsenal of virulence factors that facilitate its invasion into, and survival within, the human host. The expression of these virulence factors is controlled by the quorum sensing accessory gene regulator (Agr) system. However, a large proportion of clinical S. aureus isolates are consistently found to have a mutationally inactivated Agr system. These mutants have a survival advantage in the host but are considered irreversible mutants. Here we show, for the first time, that a fraction of Agr-negative mutants can revert their Agr activity. By serially passaging Agr-negative strains and screening for phenotypic reversion of hemolysis and subsequent sequencing, we identified two mutational events responsible for reversion: a genetic duplication plus inversion event and a poly(A) tract alteration. Additionally, we demonstrate that one clinical Agr-negative methicillin-resistant S. aureus (MRSA) isolate could reproducibly generate Agr-revertant colonies with a poly(A) tract genetic mechanism. We also show that these revertants activate their Agr system upon phagocytosis. We propose a model in which a minor fraction of Agr-negative S. aureus strains are phase variants that can revert their Agr activity and may act as a cryptic insurance strategy against host-mediated stress. IMPORTANCE Staphylococcus aureus is responsible for a broad range of infections. This pathogen has a vast arsenal of virulence factors at its disposal, but avirulent strains are frequently isolated as the cause of clinical infections. These isolates have a mutated agr locus and have been believed to have no evolutionary future. Here we show that a fraction of Agr-negative strains can repair their mutated agr locus with mechanisms resembling phase variation. The agr revertants sustain an Agr OFF state as long as they exist as a minority but can activate their Agr system upon phagocytosis. These revertant cells might function as a cryptic insurance strategy to survive immune-mediated host stress that arises during infection.

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.

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