scholarly journals Decursinol Angelate Mitigates Sepsis Induced by Methicillin-Resistant Staphylococcus aureus Infection by Modulating the Inflammatory Responses of Macrophages

2021 ◽  
Vol 22 (20) ◽  
pp. 10950
Author(s):  
Seongwon Pak ◽  
Bikash Thapa ◽  
Keunwook Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inflammatory Responses ◽  
Lethal Dose ◽  
Ectopic Expression ◽  
Chemical Components ◽  
Bacterial Killing ◽  
Methicillin Resistant ◽  
Decursinol Angelate ◽  
Tnf Α

The herbal plant Angelica gigas (A. gigas) has been used in traditional medicine in East Asian countries, and its chemical components are reported to have many pharmacological effects. In this study, we showed that a bioactive ingredient of A. gigas modulates the functional activity of macrophages and investigated its effect on inflammation using a sepsis model. Among 12 different compounds derived from A. gigas, decursinol angelate (DA) was identified as the most effective in suppressing the induction of TNF-α and IL-6 in murine macrophages. When mice were infected with a lethal dose of methicillin-resistant Staphylococcus aureus (MRSA), DA treatment improved the mortality and bacteremia, and attenuated the cytokine storm, which was associated with decreased CD38+ macrophage populations in the blood and liver. In vitro studies revealed that DA inhibited the functional activation of macrophages in the expression of pro-inflammatory mediators in response to microbial infection, while promoting the bacterial killing ability with an increased production of reactive oxygen species. Mechanistically, DA treatment attenuated the NF-κB and Akt signaling pathways. Intriguingly, ectopic expression of an active mutant of IKK2 released the inhibition of TNF-α production by the DA treatment, whereas the inhibition of Akt resulted in enhanced ROS production. Taken together, our experimental evidence demonstrated that DA modulates the functional activities of pro-inflammatory macrophages and that DA could be a potential therapeutic agent in the management of sepsis.

scholarly journals Comparison of Effectiveness of Germania Honey Compared to Manuka Honey in Methicillin-Resistant Staphylococcus aureus (MRSA) Killing

2019 ◽  
Vol 13 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Ali M. Bazzi ◽  
Ali A. Rabaan ◽  
Jaffar A. Al-Tawfiq ◽  
Bilal M. Shannak
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bacterial Species ◽  
Wound Dressings ◽  
Manuka Honey ◽  
Bacterial Killing ◽  
Methicillin Resistant ◽  
Wound Culture ◽  
Comparison Of Effectiveness

Purpose: Manuka honey is currently used in medical-grade sterile wound treatment products and has been shown to be effective in methicillin-resistant Staphylococcus aureus (MRSA) killing in vitro and in wound healing in a number of case studies and series. Locally produced honey in Pakistan and Chile have been proposed to be as effective as Manuka honey in bacterial killing in vitro, presenting potentially more accessible and affordable alternatives. In this study, we compared the effectiveness of a local Germania honey from Saudi Arabia to Manuka honey MGO 550 for in vitro killing of MRSA. Methodology: Overnight Muller Hinton broth cultures of 50 wound culture isolates of MRSA from 50 patients were incubated with a series of dilutions of Manuka honey MGO 550 and corresponding Germania honey dilutions for 24 h. Turbidity was assessed to determine whether bacterial growth had occurred, and no growth was confirmed by a further 24 h sub-culture on blood agar. Results/Key findings: Manuka honey MGO 550 was significantly more effective than Germania honey at MRSA killing at 100% v/v, 50% v/v and 25% v/v (p=0.025, 0.000265, and 0.000112 respectively) Conclusion: Manuka honey MGO 550 is significantly more effective in killing MRSA in vitro than Germania honey. Germania honey does not appear to be a promising locally produced alternative to Manuka honey for the development of honey-based wound dressings. Further experiments could determine if Germania honey is effective against other bacterial species.

Co-administration of Erythromycin and Leech Salivary Extract Alleviates Osteomyelitis in Rats Induced by Methicillin-Resistant Staphylococcus aureus

2020 ◽  
Vol 33 (04) ◽  
pp. 243-251
Author(s):  
Bahar Gerivani ◽  
Hamid Staji ◽  
Maryam Rassouli ◽  
Nooshin Ghazaleh ◽  
Abbas Javaheri Vayeghan
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Growth ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Necrosis Factor Alpha ◽  
Methicillin Resistant ◽  
Tnf Α ◽  
Factor Alpha ◽  
Α Level ◽  
Necrosis Factor

Abstract Objective Erythromycin (Ery) and leech saliva (LS) can inhibit Staphylococcus aureus growth in in vitro conditions. This study aimed to evaluate the activities and synergy between Ery and LS on chronic osteomyelitis in male Wistar rat's tibia induced by methicillin-resistant S. aureus (MRSA). Materials and Methods Four weeks after osteomyelitis induction, rats were divided into four groups including no treatment (control), Ery monotherapy (orally), LS monotherapy, or Ery + LS twice daily for 2 weeks. Staphylococcus aureus growth, pathological signs and inflammatory cytokine tumour necrosis factor-alpha (TNF-α) levels were assessed. Results Rats tolerated all therapeutic strategies well during the experiment. The Ery treatment alone significantly decreased bacterial growth, pathological signs and TNF-α levels. Leech saliva alone reduced TNF-α level significantly, but did not produce a significant reduction in bacterial growth and pathological signs. Ery + LS treatment significantly decreased bacterial growth, considerably alleviated bone pathological signs and decreased TNF-α levels compared with other groups. Statistical analysis suggested that there was a stronger efficiency and synergistic action of Ery and LS when combined against MRSA-induced osteomyelitis in rats. Clinical Significance The present study suggests that LS may have clinical utility to treat MRSA-induced osteomyelitis when combined with Ery or other therapeutics.

Detection of Lethal Dose 50 of Biofilm-producing Methicillin-resistant Staphylococcus aureus Local Isolate From Mastitis

2021 ◽  
Vol 14 (2) ◽  
pp. 14-20
Author(s):  
Abdullah Abdullazeez Sheehan ◽  
Mohammed Khudor ◽  
Fanar Isihak
Keyword(s):  
Staphylococcus Aureus ◽  
Pilot Study ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Lethal Dose ◽  
Challenge Test ◽  
Albino Rats ◽  
Protection Level ◽  
Methicillin Resistant ◽  
Starting Dose ◽  
Wistar Albino Rats

It is very important, before starting the manufacture of any vaccine from any microorganism estimation of LD₅₀ of that microorganism to determine their pathogenicity and virulence. Estimated LD₅₀ was very important to be used in challenge tests later to estimate the protection level of the manufactured vaccine in experimental animals. So, this study was aimed to estimate LD₅₀ of local methicillin-resistant Staphylococcus aureus (MRSA) bacterial isolate. A pilot study has been done to determine approximately LD₅₀ of used MRSA in the study by using different bacterial concentrations of MRSA to determine approximate LD₅₀ that can be able to kill half numbers of animals used in the study to be used later in the estimation of exact LD₅₀ by using of Up-and-Down method. Ninety Wistar albino rats have been used for this purpose, eighty-four animals which divided into fourteen groups by six animals for each group (for pilot study) and remained six animals for (Up-and-Down method). The results showed that 9 X 10¹⁰ CFU/ml was led to killing half number of animals used in the study, this dose has been used as starting dose in the Up-and-Down method to the estimation of the exact LD₅₀ dose. The results showed that 5.526 X 10¹⁰ CFU/ml was the exact LD₅₀ of local MRSA isolate, which will be used later in the challenge test to estimate the protection level of a locally prepared vaccine against MRSA isolate.

scholarly journals Comparison of Antivirulence Activities of Black Ginseng against Methicillin-Resistant Staphylococcus aureus According to the Number of Repeated Steaming and Drying Cycles

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 617
Author(s):  
Young-Seob Lee ◽  
Kwan-Woo Kim ◽  
Dahye Yoon ◽  
Geum-Soog Kim ◽  
Dong-Yeul Kwon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Bacterial Cells ◽  
Methicillin Resistant ◽  
Tnf Α ◽  
Black Ginseng ◽  
Important Virulence Factor ◽  
Korean Ginseng

Korean ginseng has been widely used in Eastern medicine for thousands of years. The contents of the compounds in ginseng roots change depending on the amount of steaming and drying, and the drying method used. Black ginseng (BG) is the Korean ginseng processed by repeated steaming and drying. In this study, 5-year-old fresh Korean ginseng roots were steamed and dried 3 or 5 times, and we investigated how many cycles of steaming and drying are preferable for antivirulence activities against methicillin-resistant Staphylococcus aureus (MRSA). As a result, the antivirulence activities was increased by the treatment of BG that was steamed and dried three times, and the effect was further increased by five-time processed BG. Moreover, an ELISA showed that the TNF-α production of RAW264.7 cells stimulated by MRSA supernatants was inhibited by subinhibitory concentrations of BG extract. The expression of Hla, staphylococcal enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB), an important virulence factor in the pathogenicity of MRSA, was found to decrease when bacterial cells were treated with BG extract. The antivirulence activities of BG were not simply due to pathogen growth inhibition; the BG extract was shown to decrease agrA, hla, sea, and seb expression in MRSA. Therefore, BG strongly reduces the secretion of the virulence factors produced by Staphylococcus aureus, suggesting that a BG-based structure may be used for the development of drugs aimed at staphylococcal virulence-related exoproteins. This study suggests that BG could be used as a promising natural compound in the food and pharmaceutical industry.

scholarly journals The Study of Quality Evaluation of A Hand Rub (Hand Sanitizer) With Who-Based-Standard Formulation and Percent Reduction of Bacteria (Percentage Kill Bacteria) In Methicillin-Resistant Staphylococcus Aureus (MRSA)

2021 ◽  
Author(s):  
Ahmad Subhan ◽  
Wasmen Manalu ◽  
Min Rahminiwati ◽  
Huda Salahudin Darusman
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Human Life ◽  
Skin Irritation ◽  
Hospital Environment ◽  
Standard Formulation ◽  
Bacterial Killing ◽  
Methicillin Resistant

The pandemic that occurred caused both by COVID-19 (currently occurring), as well as the clone of the methicillin-resistant staphylococcus aureus (MRSA) in the previous period, has really threatened human life. This condition requires materials that can break the chain of transmission from human to human and the environment to human. This study aimed to evaluate the quality of alcohol-based hand rub with WHO-based-standard formulation based on the stability of the formulation, the risk of irritation, and the ability to kill bacteria. Assessment on the presence of rancidity, clarity, discoloration, final alcohol content, and skin irritation risk was done to know the quality of product formulation. A bacterial Methicillin resistance staphylococcus aureus (MRSA) was used to assess the percentage of bacterial killing power. The selected bacteria were bacteria commonly found in the hospital environment. The results of formulation stability from four variants of level modification showed that MK.IV has good stability compared to other formulation modifications. In terms of irritation risk, twenty-three selected subjects were generally well tolerated in use. The results of the percentage kill test against MRSA showed that the percentage kill is 99.90% at 1st, 2nd, and 5th minute. The selected manufacturer's product also showed the same percentage kill value at the 1st, 2nd, and 5th minute. The results of the percentage kill test showed that the effective value for each contact time is ≥ 90%.

scholarly journals Thymol Inhibits Biofilm Formation, Eliminates Pre-Existing Biofilms, and Enhances Clearance of Methicillin-Resistant Staphylococcus aureus (MRSA) in a Mouse Peritoneal Implant Infection Model

2020 ◽  
Vol 8 (1) ◽  
pp. 99 ◽  
Author(s):  
Zhongwei Yuan ◽  
Yuyun Dai ◽  
Ping Ouyang ◽  
Tayyab Rehman ◽  
Sajjad Hussain ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inflammatory Responses ◽  
Extracellular Dna ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Mouse Infection Model ◽  
Cell Counts ◽  
First Choice

Methicillin-resistant Staphylococcus aureus (MRSA) is a common human pathogen that causes several difficult-to-treat infections, including biofilm-associated infections. The biofilm-forming ability of S. aureus plays a pivotal role in its resistance to most currently available antibiotics, including vancomycin, which is the first-choice drug for treating MRSA infections. In this study, the ability of thymol (a monoterpenoid phenol isolated from plants) to inhibit biofilm formation and to eliminate mature biofilms, was assessed. We found that thymol could inhibit biofilm formation and remove mature biofilms by inhibiting the production of polysaccharide intracellular adhesin (PIA) and the release of extracellular DNA (eDNA). However, cotreatment with thymol and vancomycin was more effective at eliminating MRSA biofilms, in a mouse infection model, than monotherapy with vancomycin. Comparative histopathological analyses revealed that thymol reduced the pathological changes and inflammatory responses in the wounds. Assessments of white blood cell counts and serum TNF-α and IL-6 levels showed reduced inflammation and an increased immune response following treatment with thymol and vancomycin. These results indicate that combinatorial treatment with thymol and vancomycin has the potential to serve as a more effective therapy for MRSA biofilm-associated infections than vancomycin monotherapy.

scholarly journals Methicillin-resistant Staphylococcus aureus-induced thrombo-inflammatory response is reduced with timely antibiotic administration

2013 ◽  
Vol 109 (04) ◽  
pp. 684-695 ◽  
Author(s):  
Adriana Vieira de Abreu ◽  
Jeffrey T. Holloway ◽  
James E. Marvin ◽  
Bjoern F. Kraemer ◽  
Guy A. Zimmerman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Whole Blood ◽  
Thrombin Generation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inflammatory Responses ◽  
Antibiotic Administration ◽  
Dependent Manner ◽  
Methicillin Resistant ◽  
Human Whole Blood ◽  
Cytokine Synthesis

SummaryMethicillin-resistant Staphylococcus aureus (MRSA) induces a prothrombotic and pro-inflammatory milieu. Although timely antibiotic administration in MRSA sepsis may improve outcomes by arresting bacterial growth, the effects of antibiotics on mitigating injurious thrombo-inflammatory cellular responses remains unexplored. Using a newly developed human whole blood model and an in vivo mouse model of MRSA infection, we examined how antibiotics inhibit MRSA induced thrombo-inflammatory pathways. Human whole blood was inoculated with MRSA. Thrombin generation and inflammatory cytokine synthesis was measured in the presence or absence of linezolid and vancomycin. C57BL/6 mice were injected with MRSA and the effect of vancomycin administration was examined. MRSA accelerated thrombin generation in a time- and concentration-dependent manner and induced the release of cytokines, including interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1. The increase in thrombin generation and inflammatory responses was mediated through the synthesis of tissue factor and cytokines, respectively, and the release of microparticles. The early administration of antibiotics restored normal thrombin generation patterns and significantly reduced the synthesis of cytokines. In contrast, when antibiotic administration was delayed, thrombin generation and cytokine synthesis were not significantly reduced. In mice infected with MRSA, early antibiotic administration reduced thrombin anti-thrombin complexes and cytokine synthesis, whereas delayed antibiotic administration did not. These data provide novel mechanistic evidence of the importance of prompt antibiotic administration in infectious syndromes.

scholarly journals Cardiac gene expression and function in a mouse model of community-acquired methicillin-resistant Staphylococcus aureus sepsis: Role of inflammatory caspases 1 and 11

2019 ◽  
Vol 17 ◽  
pp. 205873921983838
Author(s):  
Janet R Hume ◽  
Yuan Zhang ◽  
Lei Zhang ◽  
Marnie Peterson ◽  
Deborah L Carlson
Keyword(s):  
Staphylococcus Aureus ◽  
Inflammatory Mediators ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Myocardial Dysfunction ◽  
Methicillin Resistant ◽  
Tnf Α ◽  
Significant Difference ◽  
Invasive Infections ◽  
Cardiac Gene ◽  
And Function

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an important cause of invasive infections, including sepsis associated with myocardial dysfunction. Caspases 1 and 11, involved in activation of the inflammasome, have been shown to be critical in response to sepsis as well as myocardial dysfunction of numerous etiologies. We examined the survival, myocardial function, and production of inflammatory mediators in mice lacking caspases 1 and 11. Cas 1/11 KO mice demonstrated no significant difference in mortality or in cardiac shortening fraction relative to control mice. Cas 1/11 KO mice had significantly reduced upregulation of expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the heart relative to control mice after CA-MRSA infection, as well as reduced serum production of IL-1β, TNF-α, and IL-6, with no difference in IL-10 production. Other inflammatory mediators beyond IL-1β, TNF-α, and IL-6 may be involved in myocardial dysfunction in CA-MRSA sepsis.

Sign in / Sign up

Export Citation Format

Share Document