scholarly journals Isoalantolactone Enhances the Antimicrobial Activity of Penicillin G against Staphylococcus aureus by Inactivating β-Lactamase during Protein Translation

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 161 ◽  
Author(s):  
Yonglin Zhou ◽  
Yan Guo ◽  
Zhongmei Wen ◽  
Xinxin Ci ◽  
Lining Xia ◽  
...  

β-Lactamase-positive Staphylococcus aureus is one of the most prevalent multidrug-resistant pathogens worldwide and is associated with increasing threats to clinical therapeutics and public health. Here, we showed that isoalantolactone (IAL), in combination with penicillin G, exhibited significant synergism against 21 β-lactamase-positive S. aureus strains (including methicillin resistant S. aureus). An enzyme inhibition assay, a checkerboard minimum inhibitory concentration (MIC) assay, a growth curve assay, a time-killing assay, a RT-PCR assay and Circular Dichroism (CD) spectroscopy were performed on different β-lactamases or β-lactamase-positive S. aureus strains, in vitro, to confirm the mechanism of inhibition of β-lactamase and the synergistic effects of the combination of penicillin G and IAL. All the fractional inhibitory concentration (FIC) indices of penicillin G, in combination with IAL, against β-lactamase-positive S. aureus, were less than 0.5, and ranged from 0.10 ± 0.02 to 0.38 ± 0.17. The survival rate of S. aureus-infected mice increased significantly from 35.29% to 88.24% within 144 h following multiple compound therapy approaches. Unlike sulbactam, IAL inactivated β-lactamase during protein translation, and the therapeutic effect of combination therapy with IAL and penicillin G was equivalent to that of sulbactam with penicillin G. Collectively, our results indicated that IAL is a promising and leading drug that can be used to restore the antibacterial effect of β-lactam antibiotics such as penicillin G and to address the inevitable infection caused by β-lactamase-positive S. aureus.

2020 ◽  
Vol 6 (2) ◽  
pp. 128-133
Author(s):  
Asih Rahayu ◽  
Chylen Setiyo Rini ◽  
Yos Adi Prakoso ◽  
Bagus Uda Palgunadi ◽  
Muhammad Aris Munandar

Background and Aim: The massive utilization of antibiotics has increased resistant genes produced by bacteria. Many bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA), have become resistant against ampicillin (AMP). The combination of an herbal extract with AMP is expected to generate synergistic effects and may restore the susceptibility of MRSA against AMP. This study aimed to analyze the potency of Sauropus androgynous extract (SAE) as a single extract and combination with AMP against MRSA. Materials and Methods: Sauropus androgynous was extracted using 60% ethanol. SAE biochemical compounds were analyzed qualitatively and quantitatively. SAE, AMP, and SAE+AMP were tested against MRSA isolates to determine the minimum inhibitory concentration and fractional inhibitory concentration. The inhibition of penicillin-binding proteins 2a (PBP2a) was analyzed using a latex agglutination test. Further, the disruptive membrane effects of SAE, AMP, and SAE+AMP were analyzed using a scanning electron microscope. The analysis of data was conducted using SPSS version 16 with p=0.01. Results: SAE contained bioactive compounds such as phenolics and flavonoids. Further, 2 mg/mL of SAE could be used as the potential concentration against MRSA isolates in vitro. In addition, the utilization of SAE+AMP generated synergistic effects, restored the susceptibility of isolates against AMP, decreased the synthesis of PBP2a by the MRSA, and induced ultrastructural changes in the bacterial membrane. Conclusion: This study indicated that the utilization of SAE potentially inhibits the growth of MRSA through decreasing of PBP2a expression, disruption of the MRSA membrane, while the combination of SAE+AMP showed synergistic effects against MRSA.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Siti Radziah Ismail ◽  
Salwani Ismail ◽  
Zakuan Zainy Deris ◽  
Nabilah Ismail

Introduction: Trigona thoracica propolis is known to have antimicrobial properties, however its antileptospiral properties and its synergistic effects with commonly prescribed antibiotics are scarcely documented. This study aimed to evaluate the antileptospiral properties of Trigona thoracica against pathogenic Leptospira species (spp.) and to study its synergistic effects with commonly prescribed antibiotics. Materials and Methods: The tested Leptospira serovars were Australis, Bataviae, Canicola and Javanica. Aqueous extract propolis (AEP) and ethanolic extracts propolis (EEP) were used. Broth dilution methods were used to determine the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and the synergistic effects between the propolis and the tested antibiotics. The synergistic effects was evaluated by using the fractional inhibitory concentration (FIC) index. Morphological changes of the treated Leptospira were observed under a Scanning Electron Microscope (SEM). Results: The AEP and EEP were found to have antileptospiral properties against the tested Leptospira spp. The synergy result showed that only combination of AEP and penicillin G against serovar Australis has demonstrated synergistic effect with the FIC index of 0.38. Morphological study using SEM showed significant structural changes of the treated Leptospira spp. Conclusions: The result suggests that Trigona thoracica propolis could potentially be used as either a complimentary or an alternative therapeutic agent against pathogenic Leptospira spp.


2017 ◽  
Vol 242 (7) ◽  
pp. 731-743 ◽  
Author(s):  
Chiu-Fai Kuok ◽  
Sai-On Hoi ◽  
Chi-Fai Hoi ◽  
Chi-Hong Chan ◽  
Io-Hong Fong ◽  
...  

Antibiotic resistance has become a serious global concern, and the discovery of antimicrobial herbal constituents may provide valuable solutions to overcome the problem. In this study, the effects of therapies combining antibiotics and four medicinal herbs on methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Specifically, the synergistic effects of Magnolia officinalis, Verbena officinalis, Momordica charantia, and Daphne genkwa in combination with oxacillin or gentamicin against methicillin-resistant (ATCC43300) and methicillin-susceptible (ATCC25923) S. aureus were examined. In vitro susceptibility and synergistic testing were performed to measure the minimum inhibitory concentration and fractional inhibitory concentration (FIC) index of the antibiotics and medicinal herbs against MRSA and methicillin-susceptible S. aureus. To identify the active constituents in producing these synergistic effects, in silico molecular docking was used to investigate the binding affinities of 139 constituents of the four herbs to the two common MRSA inhibitory targets, penicillin binding proteins 2a (PBP2a) and 4 (PBP4). The physicochemical and absorption, distribution, metabolism, and excretion properties and drug safety profiles of these compounds were also analyzed. D. genkwa extract potentiated the antibacterial effects of oxacillin against MRSA, as indicated by an FIC index value of 0.375. M. officinalis and V. officinalis produced partial synergistic effects when combined with oxacillin, whereas M. charantia was found to have no beneficial effects in inhibiting MRSA. Overall, tiliroside, pinoresinol, magnatriol B, and momorcharaside B were predicted to be PBP2a or PBP4 inhibitors with good drug-like properties. This study identifies compounds that deserve further investigation with the aim of developing therapeutic agents to modulate the effect of antibiotics on MRSA. Impact statement Antibiotic resistant is a well-known threat to global health and methicillin-resistant Staphylococcus aureus is one of the most significant ones. These resistant bacteria kill thousands of people every year and therefore a new effective antimicrobial treatment is necessary. This study identified the herbs and their associated bioactive ingredients that can potential the effects of current antibiotics. These herbs have long history of human usage in China and have well-defined monograph in the Chinese Pharmacopeia. These indicate their relatively high clinical safety and may have a quicker drug development process than that of a new novel antibiotic. Based on the results of this study, the authors will perform further in vitro and animal studies, aiming to accumulate significant data for the application of clinical trial.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Nursenem Karaca ◽  
Görkem Şener ◽  
Betül Demirci ◽  
Fatih Demirci

AbstractCombination of various compounds and essential oils for pharmaceutical formulations withdraw attention. In this present study, it was aimed to evaluate the in vitro potential synergistic antibacterial effect of Lavandula latifolia (spike lavender) essential oil with camphor by using the checkerboard method against the human pathogens; Staphylococcus aureus and Listeria monocytogenes. Pharmacopoeia quality L. latifolia essential oil and racemic camphor were analyzed and verified by GC-FID and GC/MS, simultaneously. In vitro antibacterial activity of essential oil and camphor (MIC range: 0.16–20 mg/mL) and standard antimicrobial clarithromycin (MIC range: 0.125–16 μg/mL) were carried out by broth microdilution against S. aureus and L. monocytogenes standard strains, respectively. Resulting antibacterial effects were evaluated for their fractional inhibitory concentrations (FICs) as antagonistic, additive and synergistic effects. The analytical results showed that the major component of essential oil was linalool (45.2%) and 1,8-cineole (25.6%). Antibacterial effects of essential oil were determined as MIC 1.25–5 mg/mL. As a result of the experiments, L. latifolia essential oil–camphor combinations were identified as “synergistic (FIC ≤ 0.5), and additive (0.5 < FIC ≤ 1)” in the respective combinations, suggesting further evaluation for formulations for potential antimicrobial applications in food and pharmaceuticals.


2017 ◽  
Vol 6 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Yuchi Jia ◽  
Xiaomei Wu

Abstract Objective We aimed to evaluate the combined antibacterial effects of allicin in combination with levofloxacin and ceftriaxone on Shigella isolated from the intestinal tract in vitro. Materials and Methods Using a checkerboard design, broth microdilution assay was used to test the effects of the compounds on the organism. We also determined the MIC of the two groups of antibacterial drugs against 30 strains of Shigella and calculated the fractional inhibitory concentration (FIC) index, to judge the combination effect. Result After the combined application of allicin and ceftriaxone the MIC decreased significantly. Distribution of the FIC index was as follows: FIC ≤0.5, accounting for 10%; 0.5< FIC ≤1.0, accounting for 60%; 1 < FIC ≤2, accounting for 30%; FIC >2, percentage is zero. After combined application of allicin and levofloxacin, distribution of FIC index was as follows: FIC≤0.5, ratio is zero; 0.5< FIC ≤1, accounting for 56.7%; 1 < FIC ≤2, accounting for 43.3%; FIC >2, ratio is zero. Conclusion After the combined use of ceftriaxone, levofloxacin, and allicin, most of the tests showed synergistic effects and additive effects on Shigella, while some of them showed no correlation and no antagonistic effect.


Author(s):  
Dian Ayu Eka Pitaloka ◽  
Elin Yulinah Sukandar

Objective: The resurgence of tuberculosis (TB) caused by Mycobacterium TB (MTB) is associated with the rapid spread of multidrug-resistant,therefore, the development of new antimycobacterial agents is necessary. The aim of this study was to evaluate the antimycobacterial activity ofursolic acid (UA) when it using alone and combination with TB drugs.Methods: MTB H37Rv strain, streptomycin-rifampicin resistant strain, and isoniazid-ethambutol resistant strain were evaluated by susceptibility testusing a serial number of UA (25-150 µg/mL). Minimum inhibitory concentration (MIC) was read as minimum concentration of drugs that completelyinhibit visible growth of organism. Activities of drug combination of UA with TB drug were determined in Lowenstein-Jensen media by calculatingthe fractional inhibitory concentration index.Results: The results showed that MIC of UA was 50 µg/mL against three different strains of MTB. The combination of UA and TB drugs displayedsynergistic interaction, and no antagonism result from the combination was observed for strains of MTB.Conclusion: These results indicate that UA may serve as a promising lead compound for future antimycobacterial drug development.Keywords: Ursolic acid, Tuberculosis, Drug combination, Susceptibility test


2011 ◽  
Vol 4 (1) ◽  
pp. 22-25 ◽  
Author(s):  
M Bashir ◽  
I Yusuf ◽  
AS Kutama

Five traditional herbal preparations were sampled between May-June, 2009 in Kano. The samples were investigated for invitro antibacterial activities against clinical isolates of Staphylococcus aureus. Likewise, phytochemical screening tests were conducted to determine some of the phytochemicals present in the ethanolic and water extracts of the samples. Various concentrations of the extracts were prepared using serial doubling dilutions (5000=l/ml, 2500=g/ml, 1250=g/ml, 625=g/ml and 312.5=g/ml). All the test extracts showed slight antibacterial activity against the test organism, with ethanolic extract of sample E having the highest zone diameter of inhibition, while sample H had the lowest diameter of inhibition. The standard antibiotic disc (Gentamicin) had demonstrated the highest activity on the test organisms. The results of the Phytochemical screening revealed the presence of steroid in all the samples, tannin in samples A, C, D and E, reducing sugars in sample A, D and E respectively. The result of the minimum inhibitory concentration (MIC) was found to be above 312.5=g/ml for samples C, D and E. Keywords: Staphylococcus aureus, Herbal preparations, antibacterial activity, Phytochemical screening and minimum inhibitory concentration.


Author(s):  
Yao Hu ◽  
Wen Zhou ◽  
Chengguang Zhu ◽  
Yujie Zhou ◽  
Qiang Guo ◽  
...  

Smoking is considered a key risk factor for implant survival; however, how it interacts with the pathogens in peri-implant infections is not clear. Here, we identified that nicotine, the key component of cigarette smoking, can interact with Staphylococcus aureus and synergistically induce peri-implant infections in a rat osteolysis model. The nicotine–S. aureus combination group increased the gross bone pathology, osteolysis, periosteal reactions, and bone resorption compared to the nicotine or S. aureus single treated group (p &lt; 0.05). Nicotine did not promote the proliferation of S. aureus both in vitro and in vivo, but it can significantly upregulate the expression of staphylococcal protein A (SpA), a key virulence factor of S. aureus. The nicotine–S. aureus combination also synergistically activated the expression of RANKL (receptor activator of nuclear factor-kappa B ligand, p &lt; 0.05) to promote the development of peri-implant infections. The synergistic effects between nicotine and S. aureus infection can be a new target to reduce the peri-implant infections.


2019 ◽  
Vol 22 (4) ◽  
pp. 419-427
Author(s):  
S. Nouri Gharajalar ◽  
M. Onsori

Multidrug resistant Staphylococcus aureus strains are a major health care problem both in humans and animals. In this work we described three multiplex PCR assays for detection of clinically relevant antibiotic resistance genes in S. aureus isolated from dog dental plaques. Thirty dental plaque samples were collected; then cultural, biochemical and molecular tests performed for isolation and identification of S. aureus from samples. The antibiotic susceptibility of the isolates were checked by Kirby Bauer disc diffusion method and the prevalence of antibiotic resistance genes determined using multiplex PCR assay. As a result S. aureus was isolated from 18 dog plaque samples. Fifteen of these isolates were resistant to penicillin. The mecA gene was more prevalent than blaZ among penicillin-resistant bacteria. Ten of the isolates were resistant to tetracycline. The percentage of tetM was higher than tetK among them. Also, 10 of the isolates were resistant to cefazolin among them bla TEM detected in higher rate than blaSHV and blaOXA-1. Hence multiplex PCR assay is a suitable method for detection of antibiotic resistance patterns of S. aureus isolates.


2009 ◽  
Vol 6 (4) ◽  
pp. 683-692
Author(s):  
Baghdad Science Journal

Atotal of 75 different clinical samples were collected from different hospitals in Baghdad Biochemical and morphological characterization tests showed that forty isolates were identified as Staphylococcus aureus Antibiotic susceptibility tests of all isolates towards ten antibiotics were carried out and results showed that many isolates (97.5 %) were resistant to ?-lactam antibiotic , 70 % were resistant to Tetracyclinee , 62.5% were resistant to co-trimoxazole , 60 % were resistant to ciprofloxacin , 55% were resistant both of chloramphenicol and erythromycin , 52.5% were resistant to gentamicin , 35% were resistant to rifampicin , 10% were resistant to vancomycin . According to the above results the S.aureus I1 which is isolated from patients with osteomyelitis showed resistant to all ten antibiotics therefore was used in the followed experiments. The minimum inhibitory concentration (MIC) of S.aureus I1 vancomycin, cefotaxim , penicillin G, amoxicillin , ciprofloxacin , co-trimoxazole ,gentamicin, rifampicin was checked.The results showed that isolates had MIC between (390-12500) ?g/ml. The combination of different antibiotics with vancomycin showed synergistic effect based on the Fractional inhibitory concentration index (FIC).


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