A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide 3a-f and 6a-f were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems 7a-h were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide 6a-d with organic azides. The structures of the obtained compounds were confirmed by 1H and 13C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives 3a-f and 6a-f and 1,2,3-triazole derivatives 7a-h were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis. Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide 3a-f were shown to be biologically active, and 8-hydroxy-N-methyl-N-(prop-2-yn-1-yl)quinoline-5-sulfonamide (3c) showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC50 of 100 μM. In additional tests, compound 3c decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity.
- MeSH
- antibakteriální látky * farmakologie chemie chemická syntéza MeSH
- chinoliny * chemie farmakologie chemická syntéza MeSH
- Enterococcus faecalis účinky léků MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- protinádorové látky * farmakologie chemie chemická syntéza MeSH
- racionální návrh léčiv MeSH
- Staphylococcus aureus účinky léků MeSH
- sulfonamidy * farmakologie chemie chemická syntéza MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Antimicrobial resistance remains a global issue, hindering the control of bacterial infections. This study examined the antimicrobial properties of 2,3-N,N-diphenyl quinoxaline derivatives against Gram-positive, Gram-negative, and Mycobacterium species. Two quinoxaline derivatives (compounds 25 and 31) exhibited significant activity against most strains of Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis tested, with MIC values ranging from 0.25 to 1 mg/L. These compounds also showed effective antibacterial activity against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecium/E. faecalis (VRE) strains. They demonstrated comparable or superior activity to four current antibiotics (vancomycin, teicoplanin, daptomycin, and linezolid) against a wide range of clinically relevant isolates. Additionally, they were more effective in preventing S. aureus and E. faecalis biofilm formation compared to several other antibiotics. In summary, these two quinoxaline derivatives have potential as new antibacterial agents.
- MeSH
- antibakteriální látky * farmakologie MeSH
- biofilmy * účinky léků růst a vývoj MeSH
- chinoxaliny * farmakologie MeSH
- Enterococcus faecalis * účinky léků MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus * účinky léků MeSH
- mikrobiální testy citlivosti * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Zhodnotit soubor pacientů hospitalizovaných pro infekční endokarditidu (IE) v Komplexním kardiovaskulárním centru (KKC) FN Plzeň, posoudit změny mikrobiálního spektra a prognózu nemocných. Metodika: Retrospektivně jsme analyzovali soubor 109 pacientů, kteří byli v období 5/2011-4/2019 hospitalizováni v KKC FN Plzeň a kteří splňovali diagnózu IE podle modifikovaných Duke kritérií. Uvedený 8letý časový úsek jsme dále rozdělili do dvou 4letých období k porovnání vývoje souboru nemocných v čase. Výsledky: V souboru pacientů bylo 85 mužů a 24 žen. U 56 nemocných (51 %) se jednalo o IE nativní chlopně (NVE), u 35 pacientů (32 %) o IE chlopenní protézy (PVE) a u 18 pacientů (17 %) šlo o IE v přítomnosti kardiostimulačního nebo defibrilačního systému (CDRIE). Z 35 případů PVE bylo postiženo 8 mechanických a 27 biologických protéz (včetně 2 případů postižení katetrizačně implantované aortální chlopně - TAVI). Při srovnání období od 5/2011-4/2015s obdobím od 5/2015-4/2019 došlo k vzestupu počtu hospitalizovaných pacientů s IE o 14 %. Významně se snížil počet nemocných s NVE (35 vs. 21, p = 0,001), zatímco došlo k nárůstu počtu nemocných s PVE (10 vs. 25, statisticky významně, p = 0,0131) a CDRIE (6 vs. 12, statisticky nevýznamně, p = 0,3017). Dominantním patogenem u pacientů s NVE a CDRIE zůstává Staphylococcus aureus (32 %, respektive 33 %), u nemocných s PVE byly častěji identifikovány koaguláza negativní stafylokoky (31 %). Celková hospitalizační mortalita byla 23 %, relativně nižší u pacientů s NVE (16 %), naopak výrazně vyšší u pacientů s PVE (31 %) a CDRIE (28 %). Závěr: V této retrospektivní studii jsme potvrdili vzestup celkové incidence infekční endokarditidy. Významně se snížil počet nemocných s NVE, zatímco došlo k nárůstu počtu nemocných s PVE a CDRIE. Pacienti s PVE a CDRIE rovněž vykazují vyšší mortalitu. Dominantními patogeny IE jsou Staphylococcus aureus, koaguláza negativní stafylokoky a Enterococcus faecalis.
Aim: To assess the set of patients with infective endocarditis (IE) in Complex Cardiovascular Center (CCC) in Pilsen and evaluate changes in microbial spectrum and prognosis of patients. Methods: We used a retrospective analysis to identify 109 patients with the diagnosis of IE according to modified Duke criteria, who were hospitalised in CCC in Pilsen from May 2011 to April 2019. This eight-year time period was divided into two four-year intervals to compare the changes in the set of patients. Results: The study included 85 men and 24 women. 56 patients (51 %) had native valve endocarditis (NVE), 35 patients (32 %) had prosthetic valve endocarditis (PVE) and 18 patients (17 %) had cardiac device related infective endocarditis (CDRIE). In the PVE group, 8 mechanical and 27 biological prosthesis (including 2 cases of IE after transcatheter aortic valve implantation - TAVI) were affected. When comparing the periods of May 2011 to April 2015 with May 2015 to April 2019, we found out a 14 % increase in the number of patients with IE. The number of patients with NVE decreased significantly (35 vs. 21, p = 0,001), while the number of patients with PVE (10 vs. 25, statistically significant, p = 0,0131) and CDRIE (6 vs. 12, statistically non-significant, p = 0,3017) increased. Staphylococcus aureus remains the dominant pathogen in NVE and CDRIE group (32 % and 33 %, respectively), while in PVE patients there were more often identified coagulase negative Staphylococci as a causative microbial agent (31 %). The overall in-hospital mortality rate was 23 %, relatively lower in patients with NVE (16 %), on the contrary, significantly higher in patients with PVE (31 %) a CDRIE (28 %). Conclusion: This retrospective study confirms an increase of total incidence of infective endocarditis. The number of patients with NVE decreased significantly, while the number of patients with PVE and CDRIE increased. Patients with PVE and CDRIE also show higher mortality. The dominant pathogens are Staphylococcus aureus, coagulase negative Staphylococci and Enterococcus faecalis.
- MeSH
- bakteriální endokarditida * epidemiologie etiologie mikrobiologie mortalita MeSH
- Enterococcus faecalis MeSH
- hospitalizace MeSH
- interpretace statistických dat MeSH
- klinický obraz nemoci MeSH
- lidé MeSH
- retrospektivní studie MeSH
- senioři MeSH
- srdeční chlopně umělé mikrobiologie MeSH
- srdeční chlopně mikrobiologie MeSH
- Staphylococcus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Enterococcus faecalis is an important factor in nosocomial infections. The aim of this study was the isolation of the pathogenic genes of Enterococcus faecalis in mouth infection and the study of the expression of these genes by real-time PCR. In this study, 60 isolates of E. faecalis were isolated from oral infections. The presence and frequency of cyl, hyl, and esp genes and their expression by ionic liquid were evaluated using real-time PCR. MIC was determined by broth dilution method and biofilm production was measured, then biofilm inhibition ability and cytotoxicity test were performed by MTT method. The esp, cyl, and hyl genes were observed in 10, 11, and 2 isolates, respectively. cyl gene with the highest frequency of expression in the treated group was reduced by 1.14% under the influence of ionic liquid with methionine base. The results of MIC and Sub MIC concentrations were obtained with the effect of ionic liquid including 125 and 225 μg/mL, respectively. Amino-acid-based ionic liquids can also reduce biofilm production at sub-MIC concentrations (P < 0.05), and changes in cytotoxicity at different concentrations and over time are significant (P-value < 0.001). E. faecalis strains are genetically diverse and this indicates the polyclonal prevalence of strains in clinical specimens. Combination treatment of ionic liquid with common antimicrobial drugs has good antibacterial effects against Enterococcus species, and ionic liquid with a minimum dose can be a good alternative to single-drug treatment of Enterococcus infections.
- MeSH
- aminokyseliny MeSH
- antibakteriální látky farmakologie MeSH
- biofilmy MeSH
- Enterococcus faecalis MeSH
- grampozitivní bakteriální infekce * farmakoterapie mikrobiologie MeSH
- iontové kapaliny * farmakologie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- methionin genetika farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Biofilms that grow on implant surfaces pose a great risk and challenge for the dental implant survival. In this work, we have applied Er:YAG photoacoustic irrigation using super short pulses (Er:YAG-SSP) to remove biofilms from the titanium surfaces in the non-contact mode. Mature Enterococcus faecalis biofilms were treated with saline solution, chlorhexidine, and hydrogen peroxide, or photoacoustically with Er:YAG-SSP for 10 or 60 s. The number of total and viable bacteria as well as biofilm surface coverage was determined prior and after different treatments. Er:YAG-SSP photoacoustic treatment significantly increases the biofilm removal rate compared to saline or chemically treated biofilms. Up to 92% of biofilm-covered surface can be cleaned in non-contact mode during 10 s without the use of abrasives or chemicals. In addition, Er:YAG-SSP photoacoustic irrigation significantly decreases the number of viable bacteria that remained on the titanium surface. Within the limitations of the present in vitro model, the ER:YAG-SSP seems to constitute an efficient therapeutic option for quick debridement and decontamination of titanium implants without using abrasives or chemicals.
A series of 19 synthetic alkyl and thioalkyl glycosides derived from d-mannose, d-glucose and d-galactose and having C10-C16 aglycone were investigated for cytotoxic activity against 7 human cancer and 2 non-tumor cell lines as well as for antimicrobial potential on 12 bacterial and yeast strains. The most potent compounds were found to be tetradecyl and hexadecyl β-d-galactopyranosides (18, 19), which showed the best cytotoxicity and therapeutic index against CCRF-CEM cancer cell line. Similar cytotoxic activity showed hexadecyl α-d-mannopyranoside (5) but it also inhibited non-tumor cell lines. Because these two galactosides (18, 19) were inactive against all tested bacteria and yeast strains, they could be a target-specific for eukaryotic cells. On the other hand, β-D-glucopyranosides with tetradecyl (11) and hexadecyl (12) aglycone inhibited only Gram-positive bacterial strain Enterococcus faecalis. The studied glycosides induce changes in the lipid bilayer thickness and lateral phase separation at high concentration, as derived from SAXS experiments on POPC model membranes. In general, glucosides and galactosides exhibit more specific properties. Those with longer aglycone show high cytotoxicity and therefore, they are more promising candidates for cancer cell line targeted inhibition.
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- buněčné linie MeSH
- buňky A549 MeSH
- buňky K562 MeSH
- difrakce rentgenového záření MeSH
- Enterococcus faecalis účinky léků MeSH
- galaktosa chemická syntéza chemie farmakologie MeSH
- glykosidy chemická syntéza chemie farmakologie MeSH
- HCT116 buňky MeSH
- lidé MeSH
- lipidové dvojvrstvy chemie MeSH
- maloúhlový rozptyl MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- proliferace buněk MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- sacharidové sekvence MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Několik studií ukázalo, že infekční endokarditida způsobená bakteriemi kmene Enterococcus faecalis je třetím hlavním zdrojem infekční endokarditidy (IE). Kromě toho existuje několik důkazů, které svědčí o vztahu mezi enterokokální IE a kolorektálním karcinomem (CRC). Uvádíme kazuistiku pacienta s infekční endokarditidou způsobenou bakteriemi kmene Enterococcus faecalis spojenou s CRC. Jednasedmdesátiletý muž měl horečku, dyspnoe, ortopnoe, kašel, mírnou hemoptýzu, intermitentní rektoragii, bledé spojivky, "jemné praskání" a typický zvuk umělé chlopně. Byla mu diagnostikována bakteriemie vyvolaná Enterococcus faecalis a následně endokarditida. Kolonoskopie byla také provedena a uváděla, že má velký obstrukční maligní vřed v hepatické flexuře. Biopsie odhalila adenokarcinom. Kolorektální chirurgický tým provedl parciální kolektomii. Kromě toho byl pacient léčen s endokarditidou. Je zdůrazněn význam kolonoskopického screeningu u pacientů s infekcí E. faecalis a endokarditidou, jehož cílem je vyloučit diagnózu CRC.
Several studies have presented Enterococcus faecalis ( E. faecalis) endocarditis is the third leading source of infective endocarditis (IE). Besides, there have been several evidence in favor of relation between enterococcal IE and colorectal cancer (CRC). We report a patient with E. faecalis endocarditis associated with CRC. A 71-year-old male known to have a fever, dyspnea, orthopnea, cough, mild hemoptysis, intermittent rectorrhagea, pale conjunctivae, fine crackle, and typical sound of the artificial valve. He was diagnosed to have E. faecalis bacteremia and subsequent endocarditis. Also, colonoscopy was performed for him that reported a large obstructive malignant ulcer at hepatic flexure. The biopsy result was adenocarcinoma. The colorectal surgery team did a partial colectomy. Besides, he was treated for endocarditis. The colonoscopy screening in the patients of E. faecalis infection and endocarditis for the rule out of the diagnosis of CRC is emphasized.
- MeSH
- bakteriální endokarditida * diagnóza mikrobiologie terapie MeSH
- endokarditida diagnóza mikrobiologie terapie MeSH
- Enterococcus faecalis izolace a purifikace účinky léků MeSH
- kolonoskopie MeSH
- kolorektální nádory * diagnóza MeSH
- lidé MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Pterostilbene (PTE), a dimethylated analogue of resveratrol, mostly contained in Vitis vinifera leaves or in other plant sources is well-known for its antioxidant activity. Due to its bioavailability, low hydrophilicity and thus ability to penetrate hydrophobic biological membranes it was found to be an antimicrobial agent. These properties of PTE offer the possibility of its use in the treatment of microbial infections. The emergence of antibiotic resistance of microorganisms is often caused by their ability to form biofilm; new substances with antibiofilm activity are therefore sought. The representatives of opportunistic pathogenic gram-positive and gram-negative bacteria as well as fungi were used for the determination of minimum inhibitory concentrations (MIC50 and MIC80), minimum biofilm inhibitory concentrations (MBIC50 and MBIC80) and minimum biofilm eradication concentrations (MBEC50 and MBEC80) of PTE and commonly used antibiotics erythromycin, polymyxin B or antimycotic amphotericin B. Total biofilm biomass was investigated by crystal violet staining, and the results were confirmed using microscopic techniques. The most significant antibiofilm action was proved for gram-positive cocci, e.g., MBEC50 of PTE for all strains of Staphylococcus epidermidis tested was 25 mg/L. By contrast, the antibiotic ERM did not exhibit antibiofilm activity in most cases. The permeabilization of cell membranes of gram-positive cocci biofilm by MBIC50 and MBEC50 of PTE was confirmed by LIVE/DEAD staining using spinning disc confocal microscopy. PTE significantly influenced the ability of gram-positive cocci to form biofilm and it effectively eradicated pre-formed biofilm in vitro; its potential for the treatment of biofilm-associated infections of Staphylococcus spp. or Enterococcus faecalis is thus apparent.
- MeSH
- antibakteriální látky farmakologie MeSH
- antioxidancia farmakologie MeSH
- biofilmy účinky léků růst a vývoj MeSH
- Enterococcus faecalis účinky léků MeSH
- gramnegativní bakterie účinky léků MeSH
- grampozitivní bakterie účinky léků MeSH
- grampozitivní koky účinky léků MeSH
- listy rostlin chemie MeSH
- mikrobiální testy citlivosti MeSH
- Pseudomonas aeruginosa účinky léků MeSH
- rostlinné extrakty farmakologie MeSH
- Staphylococcus epidermidis účinky léků MeSH
- stilbeny farmakologie MeSH
- Vitis chemie MeSH
- Publikační typ
- časopisecké články MeSH
In Slovakia, dairy products made from ewes' milk have a long tradition. These products include the lactic acid product called "žinčica" which is a by-product occurring during the preparation of ewes' lump cheese. There is no information in the literature regarding the special properties of the microbiota, especially lactic acid Firmicutes, which can survive in "žinčica." From the safety aspect, enterococci are a controversial group of bacteria, and those from "žinčica" have never been tested for their properties. The "žinčica" used in our study was supplied by several different agrofarms producing ewes' lump cheese in central Slovakia. The species Enterococcus faecium (strains EF30E1, EF32E1, EF34E1, EF34E5) and Enterococcus faecalis (strains EE30E4, EE35E1, E31E2, altogether 7) were detected in samples from "žinčica" identified using MALDI-TOF spectrometry with secure genus identification/probable species identification and then confirmed by means of PCR. Enterococci were hemolysis-negative and the genes of the typical enterococcal virulence factors were mostly absent; the gelE gene was found in two E. faecium strains (EF30E1 and EF32E1), the agg gene was detected in E. faecalis EE35E1, and the esp gene was found in two E. faecalis strains (EE30E4 and EE31E2). No strains harbored the cytolysin A gene. Biofilm formation was detected in four strains (EF30E1, EF32E1, EF34E1, and EF34E5), indicating highly positive and low-grade positive biofilm formation. Enterococci were mostly susceptible to antibiotics tested for their phenotype. This is the first study to analyze enterococci in "žinčica."
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální proteiny genetika MeSH
- bezpečnost potravin * MeSH
- biofilmy růst a vývoj MeSH
- Enterococcus faecalis účinky léků genetika MeSH
- Enterococcus faecium účinky léků genetika MeSH
- Enterococcus klasifikace účinky léků patogenita MeSH
- faktory virulence genetika MeSH
- mikrobiální testy citlivosti MeSH
- mikrobiota MeSH
- ovce MeSH
- potravinářská mikrobiologie * MeSH
- sýr mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
Enterococcus faecalis is a Gram-positive facultative anaerobe involved in many fatal or refractory infections of humans. Silver, often used as silver ions (Ag+) or nanoparticles (AgNPs), is a strong and broad-spectrum antibacterial agent, but E. faecalis shows resistance against it. Despite this, the knowledge about the resistance of E. faecalis against silver is still lacking. In this study, the silver-resistant E. faecalis strains (AgR and ANR E. faecalis) were established through a serial selection method. Their biological and silver-resistant features as well as the Gene Ontology (GO) in comparison with the original E. faecalis were evaluated. The results showed that the silver-resistant E. faecalis could proliferate as original bacteria and had strong resistance against both Ag+ and AgNPs. The minimum bactericidal concentrations (MBCs) of AgNO3 on original, AgR, and ANR E. faecalis were 400 mg/L, 600 mg/L, and 500 mg/L, and the MBCs of AgNPs on these strains were 80 mg/L, 110 mg/L, and 130 mg/L, respectively. GO analysis revealed significant difference (P < 0.05) in gene expressions of biological process (BP), cellular component (CC), and molecular function (MF) among original, AgR, and ANR E. faecalis. These findings provided a significant basis for further understanding and managing the silver-resistance of E. faecalis in infection-control environments. The mechanism behind Ag+/AgNPs resistance of E. faecalis needs to be further investigated.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- bakteriální léková rezistence účinky léků genetika MeSH
- bakteriální proteiny genetika MeSH
- dusičnan stříbrný metabolismus farmakologie MeSH
- Enterococcus faecalis účinky léků genetika růst a vývoj fyziologie MeSH
- kovové nanočástice chemie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- regulace genové exprese u bakterií MeSH
- stříbro chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
