scholarly journals Study on Demethoxycurcumin as a Promising Approach to Reverse Methicillin-Resistance of Staphylococcus aureus

2021 ◽  
Vol 22 (7) ◽  
pp. 3778
Author(s):  
Qian-Qian Li ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Synergistic Effects ◽  
Penicillin Binding Protein ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Mrsa Strains ◽  
Phytochemical Components ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) has always been a threatening pathogen. Research on phytochemical components that can replace antibiotics with limited efficacy may be an innovative method to solve intractable MRSA infections. The present study was devoted to investigate the antibacterial activity of the natural compound demethoxycurcumin (DMC) against MRSA and explore its possible mechanism for eliminating MRSA. The minimum inhibitory concentrations (MICs) of DMC against MRSA strains was determined by the broth microdilution method, and the results showed that the MIC of DMC was 62.5 μg/mL. The synergistic effects of DMC and antibiotics were investigated by the checkerboard method and the time–kill assay. The ATP synthase inhibitors were employed to block the metabolic ability of bacteria to explore their synergistic effect on the antibacterial ability of DMC. In addition, western blot analysis and qRT-PCR were performed to detect the proteins and genes related to drug resistance and S. aureus exotoxins. As results, DMC hindered the translation of penicillin-binding protein 2a (PBP2a) and staphylococcal enterotoxin and reduced the transcription of related genes. This study provides experimental evidences that DMC has the potential to be a candidate substance for the treatment of MRSA infections.

scholarly journals Study on Demethoxycurcumin as a promising approach to reverse methicillin-resistance of Staphylococcus aureus

2021 ◽  
Author(s):  
Qian-Qian Li ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Atp Synthase ◽  
Methicillin Resistance ◽  
Synergistic Effects ◽  
Inhibitory Effect ◽  
Current Treatment ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Time Kill

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) has always been a thorny pathogen, posing serious threat to public health. Current treatment resort for MRSA infections is still scarce. Research on phytochemical component that can replace antibiotics with limited efficacy may be an innovative method to solve intractable MRSA infections. The present study was devoted to investigating the antibacterial activity of the natural compound demethoxycurcumin (DMC) against MRSA and exploring its possible mechanism for eliminating MRSA resistance. Methods The present study determined minimum inhibitory concentrations (MICs) of DMC, oxacillin, ampicillin and gentamicin against MRSA strains by the broth microdilution method. The synergistic effects of DMC and antibiotics were investigated by the checkerboard method and the time-kill assay. The membrane-permeabilizing agents and ATP synthase inhibitors were employed to explore their impact on the antibacterial ability of DMC. Western blot analysis and qRT-PCR were performed to detect the proteins and genes related to drug resistance and S. aureus exotoxins. Results The MIC of DMC against MRSA is 62.5 µg/ml by broth microdilution method. The synergy between DMC and gentamicin was confirmed by checkerboard method and time-kill assay. When ATP synthase inhibitors blocked the metabolic ability of bacteria, the antibacterial effect of DMC was enhanced. The production of penicillin-binding protein 2a (PBP2a) protein and related genes were reduced by DMC at sub-inhibitory concentrations. In addition, DMC hindered the translation of staphylococcal enterotoxin and the transcription of related gene. Conclusions Based on our results, DMC has a significant inhibitory effect on the vitality of MRSA, and it can be inferred that the mechanism by which DMC reverses MRSA resistance is related to the ability of DMC to block resistance determinants (PBP2a and β-lactamase) and S. aureus exotoxin. This study provides experimental evidences that DMC has the potential to be a candidate substance for the treatment of MRSA infections.

scholarly journals A Molecular Insight into the Synergistic Mechanism of Nigella sativa (Black Cumin) with β-Lactam Antibiotics against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 11 (7) ◽  
pp. 3206
Author(s):  
Lorina I. Badger-Emeka ◽  
Promise Madu Emeka ◽  
Hairul Islam M. Ibrahim
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Nigella Sativa ◽  
Synergistic Effects ◽  
Diffusion Method ◽  
Methicillin Resistant ◽  
Cell Wall Disruption ◽  
Time Kill ◽  
Insight Into

Methicillin-resistant Staphylococcus aureus (MRSA) infection is detrimental to hospitalized patients. With diminishing choices of antibiotics and the worry about resistance to colistin in synergistic combined therapy, there are suggestions for the use of herbal derivatives. This investigation evaluated the synergistic effects of Nigella sativa (NS) in combination with beta-lactam (β-lactam) antibiotics on extreme drug-resistant (XDR) MRSA isolates. NS concentrations of 10, 7.5, 5.0, 2.5, 1.0, and 0.1 µg/mL, alone and in combination with β-lactam antibiotics, were used to determine the antimicrobial susceptibility of MRSA isolates by the well diffusion method. Time–kill assays were performed using a spectrophotometer, with time–kill curves plotted and synergism ascertained by the fractional inhibitory concentration (FIC). Scanning and transmission electron microscopy were used to gain insight into the mechanism of action of treated groups. Isolates were inhibited by the NS concentrations, with differences in the zones of inhibition being statistically insignificant at p < 0.05. There were statistically significant differences in the time–kill assay for the MRSA isolates. In addition, NS combined with augmentin showed better killing than oxacillin and cefuroxime. The mechanism of action shown by the SEM and TEM results revealed cell wall disruption, which probably created interference that led to bacterial lysis.

scholarly journals Trans-Cinnamaldehyde Exhibits Synergy with Conventional Antibiotic against Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 22 (5) ◽  
pp. 2752
Author(s):  
Shu Wang ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Synergistic Effects ◽  
Regulatory Gene ◽  
Western Blot Assay ◽  
Methicillin Resistant ◽  
Wide Range ◽  
Kill Curve ◽  
Conventional Antibiotics ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide and has acquired multiple resistance to a wide range of antibiotics. Hence, there is a pressing need to explore novel strategies to overcome the increase in antimicrobial resistance. The present study aims to investigate the efficacy and mechanism of plant-derived antimicrobials, trans-cinnamaldehyde (TCA) in decreasing MRSA’s resistance to eight conventional antibiotics. A checkerboard dilution test and time–kill curve assay are used to determine the synergistic effects of TCA combined with the antibiotics. The results indicated that TCA increased the antibacterial activity of the antibiotics by 2-16-fold. To study the mechanism of the synergism, we analyzed the mecA transcription gene and the penicillin-binding protein 2a level of MRSA treated with TCA by quantitative RT-PCR or Western blot assay. The gene transcription and the protein level were significantly inhibited. Additionally, it was verified that TCA can significantly inhibit the biofilm, which is highly resistant to antibiotics. The expression of the biofilm regulatory gene hld of MRSA after TCA treatment was also significantly downregulated. These findings suggest that TCA maybe is an exceptionally potent modulator of antibiotics.

scholarly journals Ceftobiprole Is Superior to Vancomycin, Daptomycin, and Linezolid for Treatment of Experimental Endocarditis in Rabbits Caused by Methicillin-Resistant Staphylococcus aureus

2009 ◽  
Vol 54 (2) ◽  
pp. 610-613 ◽  
Author(s):  
P. Tattevin ◽  
L. Basuino ◽  
D. Bauer ◽  
B. A. Diep ◽  
H. F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Group ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Rabbit Model ◽  
Laboratory Strain ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
High Affinity

ABSTRACT Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P < 0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P < 0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

8-hydroxyquinoline-5-(N-4-chlorophenyl) sulfonamide and fluconazole combination as a preventive strategy for Candida biofilm in haemodialysis devices

2021 ◽  
Vol 70 (7) ◽  
Author(s):  
Letícia Fernandes da Rocha ◽  
Bruna Pippi ◽  
Angélica Rocha Joaquim ◽  
Saulo Fernandes de Andrade ◽  
Alexandre Meneghello Fuentefria
Keyword(s):  
Biofilm Formation ◽  
Synergistic Effects ◽  
Local Treatment ◽  
The Other ◽  
Antibiofilm Activity ◽  
Preventive Strategy ◽  
Clinical Issue ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Time Kill

Introduction. The presence of Candida biofilms in medical devices is a concerning and important clinical issue for haemodialysis patients who require constant use of prosthetic fistulae and catheters. Hypothesis/Gap Statement. This prolonged use increases the risk of candidaemia due to biofilm formation. PH151 and clioquinol are 8-hydroxyquinoline derivatives that have been studied by our group and showed interesting anti-Candida activity. Aim. This study evaluated the biofilm formation capacity of Candida species on polytetrafluoroethylene (PTFE) and polyurethane (PUR) and investigated the synergistic effects between the compounds PH151 and clioquinol and fluconazole, amphotericin B and caspofungin against biofilm cells removed from those materials. Further, the synergistic combination was evaluated in terms of preventing biofilm formation on PTFE and PUR discs. Methodology. Susceptibility testing was performed for planktonic and biofilm cells using the broth microdilution method. The checkerboard method and the time–kill assay were used to evaluate the interactions between antifungal agents. Antibiofilm activity on PTFE and PUR materials was assessed to quantify the prevention of biofilm formation. Results. Candida albicans, Candida glabrata and Candida tropicalis showed ability to form biofilms on both materials. By contrast, Candida parapsilosis did not demonstrate this ability. Synergistic interaction was observed when PH151 was combined with fluconazole in 77.8 % of isolates and this treatment was shown to be concentration- and time-dependent. On the other hand, indifferent interactions were predominantly observed with the other combinations. A reduction in biofilm formation on PUR material of more than 50 % was observed when using PH151 combined with fluconazole. Conclusion. PH151 demonstrated potential as a local treatment for use in a combination therapy approach against Candida biofilm formation on haemodialysis devices.

scholarly journals Anti-methicillin resistant Staphylococcus aureus (MRSA) activity of an acetone extract from the leaves of Canarium odontophyllum (Miq.)

2018 ◽  
Vol 7 (3) ◽  
pp. 225-229
Author(s):  
Nur Amira Mohd Shamsuddin ◽  
◽  
Dayang Fredalina Basri ◽  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Acetone Extract ◽  
Health Concern ◽  
Antimicrobial Drugs ◽  
Methicillin Resistant ◽  
Bacteriostatic Action ◽  
Broth Microdilution Method ◽  
Canarium Odontophyllum ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern that has caused nosocomial and community infections over the past decade. The emergence of multi-drug resistant strains and limitations of present antimicrobial drugs have led to continuous search for natural products as curative agents for MRSA infections. Canarium odontophyllum Miq., locally known as dabai, has been considered an alternative phytotherapeutic treatment for MRSA. The aim of this study was to evaluate the bacteriostatic activity of an acetone extract from C. odontophyllum leaves against MRSA. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract against the ATCC 33591 and Mu50 strains were determined using the broth microdilution method, and a time-kill assay was employed to assess the type of bacteriostatic action of the extract against the Mu50 strain only. The MIC and MBC values of the extract against Mu50 were 312.5 µg/ml and 625 µg/ml, respectively, whereas the MIC and MBC values for ATCC 33591 were 625 µg/ml and 1,250 µg/ml, respectively, confirming the bacteriostatic effect against both MRSA strains. A time-kill assay showed that the acetone extract of C. odontophyllum leaves exhibited concentrationdependent bacteriostatic action against the Mu50 strain at 1/2× MIC, 1× MIC and 2× MIC. However, the extract was bactericidal only at the highest concentration (4× MIC) with a reduction in cell viability of more than 3 log10 within 24 hours. These findings confirm that an acetone extract from C. odontophyllum leaves inhibited growth of MRSA at low concentration and could be utilised as an alternative anti-MRSA agent in immune uncompromised hosts

scholarly journals 204. Antagonistic Effect of Colistin on Vancomycin Activity Against Methicillin-Resistant Staphylococcus aureus in in vitro and in vivo Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S120-S121
Author(s):  
Sungim Choi ◽  
Taeeun Kim ◽  
Seongman Bae ◽  
Eunmi Yang ◽  
Su-Jin Park ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Antagonistic Effect ◽  
In Vivo Studies ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Checkerboard Assay ◽  
Mrsa Strains ◽  
Time Kill

Abstract Background There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen. Methods We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment. Results In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2). Conclusion This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.

scholarly journals Methicillin-resistant Staphylococcus aureus (MRSA) in a tertiary surgical and trauma hospital in Benghazi, Libya

2011 ◽  
Vol 5 (10) ◽  
pp. 723-726 ◽  
Author(s):  
Najat Buzaid ◽  
Abdel-Naser Elzouki ◽  
Ibrahim Taher ◽  
Khalifa Sifaw Ghenghesh
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Age Groups ◽  
Resistant Organism ◽  
Surveillance Program ◽  
Term Care ◽  
Methicillin Resistant ◽  
Mrsa Strains

Introduction: Methicillin resistant Staphylococcus aureus (MRSA) is a multidrug resistant organism that threatens the continued effectiveness of antibiotics worldwide and causes a threat almost exclusively in hospitals and long-term care settings. This study investigated the prevalence of MRSA strains and their sensitivity patterns against various antibiotics used for treating hospitalized patients in a major tertiary surgical hospital in Benghazi, Libya. Methodology: We investigated 200 non-duplicate S. aureus strains isolated from different clinical specimens submitted to the Microbiology Laboratory at Aljala Surgical and Trauma Hospital, Benghazi, Libya from April to July 2007. Isolates were tested for methicillin resistance by the oxacillin disc-diffusion assay according to Clinical and Laboratory Standards Institute guidelines. MRSA strains were tested for antimicrobial resistance (i.e., vancomycin, ciprofloxacin, erythromycin, chloramphenicol and fusidic acid) using commercial discs. Information on patient demographics and clinical disease was also collected. Results: Of the isolates examined 31% (62/200) were MRSA. No significant differences were observed in the prevalence of MRSA among S. aureus from females or males or from different age groups. Most MRSA were isolated from burns and surgical wound infections. Antibiotic resistance patterns of 62 patients with MRSA to vancomycin, ciprofloxacin, fusidic acid, chloramphenicol and erythromycin were 17.7%, 33.9%, 41.9%, 38.7% and 46.8% of cases, respectively. Conclusion: MRSA prevalence in our hospital was high and this may be the case for other hospitals in Libya. A sound surveillance program of nosocomial infections is urgently needed to reduce the incidence of infections due to MRSA and other antimicrobial-resistant pathogens in Libyan hospitals.

scholarly journals In Vitro Antibacterial, Anti-Adhesive and Anti-Biofilm Activities of Krameria lappacea (Dombey) Burdet & B.B. Simpson Root Extract against Methicillin-Resistant Staphylococcus aureus Strains

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 428
Author(s):  
Carlo Genovese ◽  
Floriana D’Angeli ◽  
Francesco Bellia ◽  
Alfio Distefano ◽  
Mariarita Spampinato ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
High Resolution Mass Spectrometry ◽  
Current Knowledge ◽  
Biological Activities ◽  
Root Extract ◽  
Methicillin Resistant ◽  
Broth Microdilution Method ◽  
Mrsa Strains ◽  
Adhesion And Invasion

Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious threat to public health, due to its large variety of pathogenetic mechanisms. Accordingly, the present study aimed to investigate the anti-MRSA activities of Krameria lappacea, a medicinal plant native to South America. Through Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass spectrometry, we analyzed the chemical composition of Krameria lappacea root extract (KLRE). The antibacterial activity of KLRE was determined by the broth microdilution method, also including the minimum biofilm inhibitory concentration and minimum biofilm eradication concentration. Besides, we evaluated the effect on adhesion and invasion of human lung carcinoma A549 cell line by MRSA strains. The obtained results revealed an interesting antimicrobial action of this extract, which efficiently inhibit the growth, biofilm formation, adhesion and invasion of MRSA strains. Furthermore, the chemical analysis revealed the presence in the extract of several flavonoid compounds and type-A and type-B proanthocyanidins, which are known for their anti-adhesive effects. Taken together, our findings showed an interesting antimicrobial activity of KLRE, giving an important contribution to the current knowledge on the biological activities of this plant.

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