Növekvő antibiotikum rezisztencia: fokozódó veszélyek és megoldási lehetőségek
(Gyógygomba kivonatok, mint az antibiotikumok szövetségesei)
Az antibiotikum rezisztencia jelentős európai és globális közegészségügyi probléma, mely nagy részben az antibiotikumok nem megfelelő felhasználására vezethető vissza. Ezért azok a betegek, akik olyan fertőzéseket szenvednek el, amelyeket sokszor számos antibiotikummal szemben ellenálló (multirezisztens) baktériumok okoznak, kevés esélyük van a gyógyulásra.
Német kutatók egy most megjelenő tanulmányban arra hívták fel a figyelmet, hogy a tüdőgyulladás következtében elhunyt idős emberek jelentős része az antibiotikumokkal szembeni rezisztenciának köszönhetik azt, hogy betegségük végzetessé vált. (Growing Antibiotic Resistance in Fatal Cases of Staphylococcal Pneumonia in the Elderly. Adv Exp Med Biol. 2016 Jan 9. [Epub ahead of print])
Ezeknek a tényeknek a tükrében nem hanyagolhatóak el azok az elmúlt években megjelent kutatások, amelyek nem csak azt mutatták ki, hogy számos természetben élő gyógygomba kivonata antibakteriális hatást tanúsít a baktériumok széles körével szemben, hanem azt is, hogy egyes gyógygomba kivonatok fokozzák a hagyományos antibiotikumok antibakteriális hatását is, ha azokat együtt alkalmazzák a gyógyszerekkel.( Int J Med Mushrooms. 2012;14(5):481-90.
Naturally occurring medicinal mushroom-derived antimicrobials: a case-study using Lingzhi or ReishiGanoderma lucidum (W. Curt.:Fr.) P. Karst. (higher Basidiomycetes).)
Magyarországon már a gyakorlatban is tapasztalták betegek, hogy nagy dózisú gyógygomba kivonatok keverékének alkalmazása életmentőnek bizonyult abban az esetben, amikor az antibiotikumok eredménytelennek voltak, pl. elfertőződött sebek kezelésében.
A gyógygomba kivonatoknak kutatása szerteágazó, kimutatták azok jótékony hatását pl. az immunrendszer stabilizálásában, a kiegészítő rákterápiában, ill. szív és érrendszer problémái esetén is. Valószínűleg az egyre több kutatási eredmény ellenére jelentőségüket még mindig alábecsülik: ezen változtathat az a tény, hogy az életünket veszélyeztető egyre agresszívabb baktérium törzsek ellen hatékonyabb fegyverekre lesz szükségünk.
Dokumentumfilm: YouTube: https://youtu.be/OxknHgHJjNk
Adv Exp Med Biol. 2016 Jan 9. [Epub ahead of print]
Growing Antibiotic Resistance in Fatal Cases of Staphylococcal Pneumonia in the Elderly.
Older people are often especially susceptible to pneumonia and bacteria may develop resistance to antibiotics quicker in the elderly, whose immune systems gradually diminish. This study analyses, retrospectively, resistance to antibiotics in high-risk elderly patients with fatal pneumonia. Records of all patients aged over 65 who did not survive a bout with pneumonia were gathered from the records of the Department of Pneumology of HELIOS Clinic in Wuppertal, Germany from the period of 2004-2014. Susceptibility testing was executed for the study population, whose pneumonia was triggered by various kinds of bacteria. We detected 936 pneumonia patients of the overall mean age of 68.0 ± 13.6 years, with the following pneumonia types: 461 (49.3 %) community-acquired, 354 (37.8 %) nosocomial-acquired, and 121 (12.9 %) aspiration pneumonia. There were 631 (67.4 %) males and 305 (32.6 %) females there. We identified 672 (71.8 %) patients who had a high risk for pneumonia, especially staphylococcal pneumonia (p < 0.0001). The elderly patients had a higher risk of dying from pneumonia (2.9 odds ratio, 95 % confidence interval 1.8-4.6; p < 0.0001); of the 185 pneumonia-related deaths, 163 (88.1 %) were in the elderly. In those with fatal staphylococcal pneumonia, a high antibiotic resistance rate was found for piperacillin-tazobactam (p = 0.044), cefuroxime (p = 0.026), cefazolin (p = 0.043), levofloxacin (p = 0.018), erythromycin (p = 0.004), and clindamycin (p = 0.025). We conclude that elderly patients with staphylococcal pneumonia show resistance to common antibiotics. However, no significant antibiotic resistance could be ascribed for other types of pneumonia in these patients.
Naturally occurring medicinal mushroom-derived antimicrobials: a case-study using Lingzhi or ReishiGanoderma lucidum (W. Curt.:Fr.) P. Karst. (higher Basidiomycetes).
Antibacterial activity of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum, collected from Central India was evaluated against four bacterial pathogens. Ethyl alcohol and water extracts of fruit body powder were tested using the disc diffusion method against Staphylococcus aureus, Klebsiella pneumoniae, Bacillus cereus, and Pseudomonas aeruginosa. It was noted that the aqueous extract inhibited growth of pathogenic bacteria. The combined effect of fruit body extract with synthetic antibiotic discs was found to increase the activity significantly more than the antibiotics alone. The present study is an attempt to assess antibacterial activity of extracts of G. lucidum singly and in combination. The combination of G. lucidum with commercial antibiotics proves that it enhances antibacterial activity.
Int J Antimicrob Agents.. 2015 Dec;46(6):666-73. doi: 10.1016/j.ijantimicag.2015.09.006. Epub 2015 Oct 22.
Apigenin as an anti-quinolone-resistance
We previously reported the first 'reverse antibiotic' (RA), nybomycin (NYB), which showed a unique antimicrobial activity against Staphylococcus aureus strains. NYB specifically suppressed the growth of quinolone-resistant S. aureus strains but was not effective against quinolone-susceptible strains. Although NYB was first reported in 1955, little was known about its unique antimicrobial activity because it was before the synthesis of the first quinolone ('old quinolone'), nalidixic acid, in 1962. Following our re-discovery of NYB, we looked for other RAs among natural substances that act on quinolone-resistant bacteria. Commercially available flavones were screened against S. aureus, including quinolone-resistant strains, and their minimum inhibitory concentrations (MICs) were compared using the microbroth dilution method. Some of the flavones screened showed stronger antimicrobial activity against quinolone-resistant strains than against quinolone-susceptible ones. Amongst them, apigenin (API) was the most potent in its RA activity. DNA cleavage assay showed that API inhibited DNA gyrase harbouring the quinolone resistance mutation gyrA(Ser84Leu) but did not inhibit 'wild-type' DNA gyrase that is sensitive to levofloxacin. An API-susceptible S. aureus strain Mu50 was also selected using agar plates containing 20mg/L API. Whole-genome sequencing of selected mutant strains was performed and frequent back-mutations (reverse mutations) were found among API-resistant strains derived from the API-susceptible S. aureus strains. Here we report that API represents another molecular class of natural antibiotic having RA activity against quinolone-resistant bacteria.
Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Apigenin; Nybomycin; Quinolone resistance; Reverse antibiotic; gyrA mu
Indian J Exp Biol. 2015 Jan;53(1):36-43.
Phytochemical and antimicrobial activities of Himalayan Cordyceps sinensis (Berk.) Sacc.
This study evaluated the phytochemical and antimicrobial activities and also quantified bioactive nucleoside using high performance thin layer chromatography (HPTLC) of five extracts of Indian Himalayan Cordyceps sinensis prepared with different solvents employing accelerated solvent extraction (ASE) technique. The phytochemical potential of these extracts was quantified in terms of total phenolic and total flavonoid content while antioxidant activities were determined by 1,1-diphenyl-2-pycryl-hydrazyl (DPPH) and 2,2 -azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric-reducing antioxidant power (FRAP) assays. Total reducing power (TRP) was determined by converting iron (III) into iron (II) reduction assay. CS(50%Alc) (15.1 ± 0.67mg/g of dry extract) and CS(100%Alc) (19.3 ± 0.33 mg/g of dry extract) showed highest phenolic and flavonoid content, respectively while CS(Aq) extract showed maximum antioxidant activity and the highest concentration of the three nucleosides (adenine 12.8 ± 0.49 mg/g, adenosine 0.36 ± 0.28 mg/g and uracil 0.14 ± 0.36 mg/g of dry extract) determined by HPTLC. The evaluation of extracts for antimicrobial activity against gram-negative and gram-positive bacterial strains showed CS(25%Alc), CS(75%Alc) and CS(100%Alc) extract to be more effective against E. coli, P. aerugenosa and B. subtilis giving 9, 7 and 6.5 mm of zone of inhibition (ZOI) in 93.75, 93.75 and 45 μg concentration, respectively, whereas CS(Aq) extract showed minimal inhibition against these.
Int J Med Mushrooms. 2013;15(2):165-74.
In vitro anti-Helicobacter pylori effects of medicinal mushroom extracts, with special emphasis on the Lion's Mane mushroom, Hericium erinaceus (higher Basidiomycetes).
Although the medicinal mushroom Hericium erinaceus is used extensively in traditional Chinese medicine to treat chronic superficial gastritis, the underlining pharmaceutical mechanism is yet to be fully understood. In this study, minimum inhibitory concentration (MIC) values of extracts prepared from the fruiting bodies of 14 mushroom species (H. erinaceus, Ganoderma lucidum, Cordyceps militaris, Pleurotus eryngii, P. ostreatus, Agrocybe aegerita, Lentinus edodes, Agaricus brasiliensis, A. bisporus, Coprinus comatus, Grifola frondosa, Phellinus igniarius, Flammulina velutipes, and Hypsizygus marmoreus) were determined against Helicobacter pylori using laboratory strains of ATCC 43504 and SS1 as well as 9 clinical isolates via an in vitro microplate agar diffusion assay. Ethanol extracts (EEs) of 12 mushrooms inhibited the growth of H. pylori in vitro, with MIC values 10 mg/mL). MIC values of ethyl acetate fractions (EAFs) of H. erinaceus against 9 clinical isolates of H. pylori ranged between 62.5 and 250 µg/mL. The bacteriostatic activity of EAFs was found to be concentration-dependant, and the half maximal inhibitory concentration and minimum bactericidal concentration values for H. pylori ATCC 43504 were 73.0 and 200 µg/mL, respectively. The direct inhibitory effect of EEs and EAFs of H. erinaceus against H. pylori could be another pharmaceutical mechanism of medicinal mushrooms-besides the immunomodulating effect of polysaccharides, suggested previously-in the treatment of H. pylori-associated gastrointestinal disorders. Further research to identify the active component(s) is currently undertaking in our laboratory
J Ethnopharmacol. 2015 Sep 10. pii: S0378-8741(15)30130-6. doi: 10.1016/j.jep.2015.09.004. [Epub ahead of print]
Anti-Helicobacter pylori activity of bioactive components isolated from Hericium erinaceus.
The fungus Hericium erinaceus (Bull.) Pers is used in Chinese traditional medicine to treat symptoms related to gastric ulcers. Different extracts from the fungus were assessed for anti-Helicobacter pylori activity to investigate the antibacterial activity of the ethanol extracts from H. erinaceus and verify the traditional indication of use.
MATERIALS AND METHODS:
The fruiting bodies of H. erinaceus were concentrated with ethanol by HPD-100 macroporous resin and the whole extract was partitioned by petroleum ether and chloroform to afford fractions with using a silica gel column. Several pure compounds of petroleum ether extracts were obtained and analyzed using nuclear magnetic resonance (NMR). The activity of the extracts and fractions towards H. pylori was assessed by the microdilution assay and by the disk diffusion assay in vitro. From the most active fraction, two pure compounds were isolated and identified as the main components with anti-H. pylori activity from the fungus H. erinaceus. The cytotoxicity of these two compounds against the human erythroleu-kemia cell line K562was also evaluated.
The crude ethanol extracts from the fungus H. erinaceus were inhibitory to H. pylori. The petroleum ether extracts (PE1s, PE2s) and the chloroform extracts (TEs) demonstrated strong inhibition to H.r pylori. The inhibition of H.r pylori was observed through an agar dilution test with minimal inhibition concentration (MIC) values from 400μg/mL to 12.5µg/mL. Two pure compounds, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone and 2,5-bis(methoxycarbonyl)terephthalic acid were isolated from the petroleum ether fractions and identified using 1HNMR and 13CNMR spectra analysis. The MIC value for 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone was 12.5-50µg/mL and the MIC value for 2,5-bis(methoxycarbonyl)terephthalic acid was 6.25-25µg/mL. Both two compounds showed weak cytotoxicity against K562 with IC50<200mM.
This study revealed that the extracts from petroleum ether contribute to the anti-Helicobacter pylori activity. The compounds obtained from petroleum ether extracts, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone and 2,5-bis(methoxycarbonyl)terephthalic acid, inhibit the rowth of Helicobacter pylori.
Copyright © 2015. Published by Elsevier Ireland Ltd.
Biomed Res Int. 2014;2014:743812. doi: 10.1155/2014/743812. Epub 2014 Jul
Exopolysaccharide from Ganoderma applanatum as a promising bioactive compound with cytostatic and antibacterial properties.
A new exopolysaccharide preparation isolated from stationary cultures of the white rot fungus Ganoderma applanatum (GpEPS) was tested in terms of its bioactive properties including its cytotoxic and immunostimulatory effect. The results indicate that the tested GpEPS (at concentrations above 22.85 µg/mL and 228.5 µg/mL) may exhibit selective activity against tumor cells (cell lines SiHa) and stimulate production of TNF-α THP-1-derived macrophages at the level of 752.17 pg/mL. The GpEPS showed antibacterial properties against Staphyloccoccus aureus and a toxic effect against Vibrio fischeri cells (82.8% cell damage). High cholesterol-binding capacity and triglycerides-binding capacity (57.9% and 41.6% after 24 h of incubation with the tested substances, resp.) were also detected for the investigated samples of GpEPS