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1.
World J Microbiol Biotechnol ; 35(8): 127, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375931

RESUMO

Aeromonas hydrophila is a Gram-negative bacterium that causes serious infections in aquaculture and exhibits significant multidrug resistance. The LysR-type transcriptional regulator (LTTR) family proteins are a well-known group of transcriptional regulators involved in diverse physiological functions. However, the role of LTTRs in the regulation of bacterial resistance to antibiotics is still largely unknown. In this study, to further investigate the role of four putative LTTR family proteins (A0KIU1, A0KJ82, A0KPK0, and A0KQ63) in antibiotic resistance in A. hydrophila, their genes were cloned and overexpressed in engineered Escherichia coli. After the optimization of experimental conditions including incubation time, temperature, and IPTG concentration, these proteins were successfully purified, and their specific antibodies against mice were obtained. Using western blot analysis, we found that these LTTR family proteins were downregulated in A. hydrophila following antibiotic treatment, indicating that they may be involved in the regulation of antibiotic resistance. Additionally, minimum inhibitory concentration (MIC) assays of chloramphenicol (CM), chlortetracycline (CTC), ciprofloxacin (CF), furazolidone (FZ), and balofloxacin (BF) in E. coli showed that overexpression of these LTTRs led to increased sensitivity to several antibiotics. To further validate their functional role in antibiotic resistance, we demonstrated that bacteria with loss of A0KQ63 (ΔAHA_3980) exhibited multi-drug resistance properties. Our results indicate that these LTTR family proteins may play an important role in the antibiotic resistance of A. hydrophila, and the that underlying mechanisms controlling antibiotic resistance should be further investigated.


Assuntos
Aeromonas hydrophila/efeitos dos fármacos , Aeromonas hydrophila/genética , Farmacorresistência Bacteriana , Regulação Bacteriana da Expressão Gênica , Genes Reguladores , Fatores de Transcrição/metabolismo , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Western Blotting , Clonagem Molecular , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Deleção de Genes , Expressão Gênica , Perfilação da Expressão Gênica , Genes Bacterianos , Camundongos , Testes de Sensibilidade Microbiana , Fatores de Transcrição/análise , Fatores de Transcrição/genética
2.
Phys Chem Chem Phys ; 21(32): 17821-17835, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31373340

RESUMO

The rise of New Delhi metallo-beta-lactamase-1 (NDM-1) producers is a major public health concern due to carbapenem resistance. Infections caused by carbapenem-resistant enterobacteria (CRE) are classified as a serious problem. To understand the structure and function of NDM-1, an amino acid replacement approach is considered as one of the methods to get structural insight. Therefore, we have generated novel mutations (N193A, S217A, G219A and T262A) near active sites and an omega-like loop to study the role of conserved residues of NDM-1. The minimum inhibitory concentrations (MICs) of ampicillin, imipenem, meropenem, cefotaxime, cefoxitin and ceftazidime for all mutants were found to be reduced 2 to 6 fold, compared to a wild type NDM-1 producing strain. The Km values increased while Kcat and Kcat/Km values were decreased compared to wild type. The affinity as well as the catalysis properties of these mutants were reduced considerably for imipenem, meropenem, cefotaxime, cefoxitin, and ceftazidimem compared to wild type, hence the catalytic efficiencies (Kcat/Km) of all mutant enzymes were reduced owing to the poor affinity of the enzyme. The IC50 values of these mutants with respect to each drug were reduced compared to wild type NDM-1. MD simulations and docking results from the mutant protein models, along with the wild type example, showed stable and consistent RMSD, RMSF and Rg behavior. The α-helix content values of all mutant proteins were reduced by 13%, 6%, 14% and 9% compared to NDM-1. Hence, this study revealed the impact role of active sites near residues on the enzyme catalytic activity of NDM-1.


Assuntos
Antibacterianos/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , beta-Lactamases/química , Antibacterianos/farmacologia , Biocatálise , Domínio Catalítico , Farmacorresistência Bacteriana , Cinética , Testes de Sensibilidade Microbiana , Mutagênese Sítio-Dirigida , Mutação , Ligação Proteica , Estrutura Secundária de Proteína , Termodinâmica , beta-Lactamases/genética , beta-Lactamases/metabolismo
3.
Pestic Biochem Physiol ; 158: 185-200, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31378356

RESUMO

The present work describes the antimicrobial action of 25 monoterpenes (six hydrocarbons, five ketones, two aldehydes, six alcohols and six acetate analogues) against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus and antifungal activity against Aspergillus flavus. The antibacterial activity was evaluated by broth microdilution technique as a minimum inhibitory concentration (MIC) and the antifungal activity was performed by mycelia radial growth technique as the effective concentration causing 50% inhibition of the mycelial growth (EC50). The results showed that thymol and α-terpineol were the most potent against E. coli (MIC = 45 and 55 mg/L, respectively) and S. aureus (MIC = 135 and 225 mg/L, respectively). The results also showed that thymol displayed the maximum antifungal action against A. flavus with EC50 20 mg/L. Furthermore, the antioxidant activity was determined using N,N-dimethyl-1,4-phenylenediamine (DMPD) and the results showed that geraniol were the most potent compound (IC50 = 19 mg/L). Molecular docking studies indicated that the compounds displayed different binding interactions with the amino acid residues at the catalytic sites of N5-carboxyaminoimidazole synthetase and oxysterol binding protein Osh4 enzymes. Non-covalent interactions including van der Waals, hydrogen bonding as well as hydrophobic were observed between the compounds and the enzymes. A significant relationship was found between the docking score and the biological activity of the tested monoterpenes compared to the ceftriaxone and carbendazim as standard bactericide and fungicide, respectively. In silico ADMET properties were also performed and displayed potential for the development of promising antimicrobial agents. For these reasons, these compounds may be considered as potential ecofriendly alternatives in food preservation to delay or prevent the microbial infection and prolong the shelf life of food products.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Monoterpenos/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/química , Cicloexenos/química , Cicloexenos/farmacologia , Escherichia coli/efeitos dos fármacos , Hidrocarbonetos/química , Hidrocarbonetos/farmacologia , Testes de Sensibilidade Microbiana , Monoterpenos/química , Monoterpenos/farmacologia , Staphylococcus aureus/efeitos dos fármacos
4.
Shokuhin Eiseigaku Zasshi ; 60(3): 45-51, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31391410

RESUMO

This study aimed to survey the trend of antimicrobial resistance in Escherichia coli obtained from retail meat. We examined the susceptibilities of 1,115 E. coli isolates obtained from chicken, beef, pork, venison, and wild boar meat from 2011 to 2017 in Tokyo to 14 antimicrobials (ampicillin, cefotaxime (CTX), streptomycin, gentamicin, kanamycin, tetracycline (TC), chloramphenicol, nalidixic acid, ciprofloxacin, sulfamethoxazole-trimethoprim, fosfomycin, amikacin, imipenem, and meropenem). Of all the tested isolates, 18.7% (135/721) isolates from chicken, 77.0% (117/152) from beef, 46.6% (89/187) from pork, 100% (28/28) from venison, and 92.6% (25/27) from wild boar meat were susceptible to all tested antimicrobials. Furthermore, TC resistance was the most common, with rates as high as 56.7% (409/721) and 40.6% (76/187) in the isolates from chicken and pork, respectively. CTX resistance was detected in 4.9% (25/506) of the isolates from domestic chicken and 23.7% (51/215) of the isolates from imported chicken. Moreover, CTX resistance rate in isolates from domestic chicken was significantly lower in 2016 (0.9%, 1/111) and in 2017 (0.8%, 1/121) than in 2012 (10.6%, 17/161). In conclusion, E. coli isolates from retail meat were most commonly resistant to TC, and CTX resistance was higher in E. coli isolates from imported chicken than in E. coli isolates from domestic chicken.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Microbiologia de Alimentos , Carne/microbiologia , Animais , Bovinos , Galinhas , Cervos , Testes de Sensibilidade Microbiana , Prevalência , Suínos , Tóquio
5.
BMC Vet Res ; 15(1): 272, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370843

RESUMO

BACKGROUND: Ceftiofur Sodium is widely used in China. Our aim was to determine Ceftiofur Sodium activity and optimize dosing regimens against the pathogen Haemophilus parasuis using an in vitro and ex vivo pharmacokinetics/pharmacodynamics modeling approach. By adopting these strategies, we wanted to extend the effective life of Ceftiofur Sodium in reduce drug-resistance in pigs. RESULTS: We established an H. parasuis infection model in pigs, and assessed the pharmacokinetics of Ceftiofur Sodium in both healthy and infected animals. After Ceftiofur Sodium (10 mg/kg, i.m.) administration to healthy and H. parasuis-infected pigs, plasma based desfuroylceftiofur (a metabolite of Ceftiofur Sodium) was measured by High Performance Liquid Chromatography. The pharmacokinetics of Ceftiofur Sodium (desfuroylceftiofur) was consistent with a two-compartment open model, with first-order absorption. We observed no significant differences (P > 0.05) in pharmacokinetic parameters between healthy and infected pigs. Pharmacodynamics data showed that Ceftiofur Sodium was highly inhibitory against H. parasuis, with MIC, MBC, and MPC values of 0.003125, 0.0125 and 0.032 µg/mL, respectively. Desfuroylceftiofur in plasma also had strong bactericidal activity. Almost all H. parasuis cultured in plasma medium of Ceftiofur Sodium-inoculated healthy pigs, at each time point, were killed within 24 h. A weaker antibacterial activity was measured in infected-pig plasma medium at 18, 24, 36, and 48 h, after Ceftiofur Sodium inoculation. Pharmacokinetic parameters were combined with ex vivo pharmacodynamic parameters, and the bacteriostatic effect (36.006 h), bactericidal effect (71.637 h) and clearance (90.619 h) within 24 h, were determined using the Hill equation. Dose-calculation equations revealed the optimal dose of Ceftiofur Sodium to be 0.599-1.507 mg/kg. CONCLUSIONS: There were no significant differences in Ceftiofur Sodium pharmacokinetic parameters between healthy and infected pigs, although pharmacokinetics/pharmacodynamics fitting curves showed obviously differences. The optimal dose of Ceftiofur Sodium was lower than recommended (3 mg/kg), which may provide improved treatments for Glässers disease, with lower drug-resistance possibility.


Assuntos
Cefalosporinas , Infecções por Haemophilus/veterinária , Modelos Biológicos , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/farmacocinética , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Infecções por Haemophilus/tratamento farmacológico , Infecções por Haemophilus/microbiologia , Haemophilus parasuis/efeitos dos fármacos , Suínos , Doenças dos Suínos/tratamento farmacológico , Doenças dos Suínos/microbiologia
6.
Chem Pharm Bull (Tokyo) ; 67(8): 810-815, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366830

RESUMO

Helicobacter pylori (H. pylori) infection is common and can result in gastric and duodenal ulcers, and in some cases, gastric lymphoma and cancer. Omeprazole (OMP)-in combination with clarithromycin (CLR), amoxicillin (AMX), tinidazole (TND), or metronidazole (MET)-is used in double or triple combination therapy for eradication of H. pylori. However, the roles of the drugs other than OMP are not clearly understood. Therefore, in the present study, we aimed to investigate any effects of these drugs on OMP metabolism by wild-type CYP2C19 using spectroscopy and enzyme kinetics. The dissociation constants (Kd) for CYP2C19 with OMP, CLR, AMX, TND, and MET were 8.6, 126, 156, 174, and 249 µM, respectively. The intrinsic clearance of OMP was determined to be 355 mL/min/µmol of CYP2C19. Metabolism of OMP was significantly inhibited by 69, 66, 28, and 40% in the presence of CLR, TND, AMX, and MET, respectively. Moreover, the combination of CLR and TND resulted in 76% inhibition of OMP metabolism, while the combination of AMX and MET resulted in 48% inhibition of OMP metabolism. Both combinations of drugs not only have antibacterial effects, but also enhance the effect of OMP by inhibiting its metabolism by CYP2C19. These results indicate that drug-drug interactions of co-administered drugs can cause complex effects, providing a basis for OMP dose adjustment when used in combination therapy for H. pylori eradication.


Assuntos
Antibacterianos/farmacologia , Citocromo P-450 CYP2C19/metabolismo , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Omeprazol/farmacologia , Amoxicilina/química , Amoxicilina/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Cromatografia Líquida de Alta Pressão , Claritromicina/química , Claritromicina/farmacologia , Citocromo P-450 CYP2C19/química , Combinação de Medicamentos , Humanos , Metronidazol/química , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Omeprazol/antagonistas & inibidores , Omeprazol/metabolismo , Tinidazol/química , Tinidazol/farmacologia
7.
Mem Inst Oswaldo Cruz ; 114: e190079, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31411309

RESUMO

A total of 124 Neisseria gonorrhoeae isolates recovered during a 12-year period (2003-2015) from outpatients assisted at Centro de Referência e Treinamento DST/AIDS-CRT of São Paulo city, Brazil, were analysed. The following resistance rates were observed: penicillin-59.6%, ciprofloxacin-15.3%, and azithromycin-6.7%. Although reduced susceptibility to these drugs was observed since 2003, no ceftriaxone-resistant isolates were detected. Ciprofloxacin- and azithromycin non-susceptible isolates were grouped in 11 clusters. Mutations were detected in GyrA and ParC of isolates 124 and 260, and a C2611T substitution on 23S rRNA alleles was also observed in isolate 260. Both isolates belonged to ST1901/ST6210 (MSLT/NG-MAST schemes).


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Mutação , Fatores de Tempo , População Urbana
8.
J Microbiol Immunol Infect ; 52(4): 654-662, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31446929

RESUMO

BACKGROUND/PURPOSE: Diabetes is associated with increased mortality in Acinetobacter baumannii (AB) complex infection. This study investigated the risk factors and relationship of diabetic status and glycemic indices to mortality in patients with carbapenem-resistant (CR) AB complex bacteremia. METHODS: Relationship of glycemic indices to mortality were compared in adult diabetes (DM) and nondiabetes (non-DM) patients with CRAB complex bacteremia hospitalized from January 2010 to December 2015 in MacKay Memorial Hospital, Taiwan. RESULTS: Of 317 patients with CRAB complex bacteremia, 146 (46.06%) had diabetes. DM patients were elderly (mean age of 69.23 years) and the mortality rate was higher (64.38% vs. 52.05%, p = 0.036) than in non-DM patients. By multivariate analysis, septic shock was associated with increased mortality in DM patients. Hypoglycemia was associated with increased mortality in non-DM patients only (100% vs. 50.33%, p = 0.006). The lowest mortality was for the blood glucose range 70-100 mg/dL in non-DM patients (43.24%) and 100-140 mg/dL for DM patients (56.52%). Increased glycemic variability (coefficient of variation (CV) > 40% compared to < 20%) was associated with increased mortality in non-DM patients (86.36% vs. 47.12%, p = 0.003). CONCLUSION: Effects of dysglycemia on mortality due to CRAB complex bacteremia differ according to diabetic status. Mortality was higher in DM patients. In non-DM patients, hypoglycemia and increased CV were associated with increased mortality. The lowest mortality was for the blood glucose range 70-100 mg/dL in non-DM patients and 100-140 mg/dL for DM patients.


Assuntos
Infecções por Acinetobacter/mortalidade , Bacteriemia/mortalidade , Glicemia/análise , Carbapenêmicos/farmacologia , Complicações do Diabetes/microbiologia , Complicações do Diabetes/mortalidade , Farmacorresistência Bacteriana , Infecções por Acinetobacter/sangue , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bacteriemia/sangue , Bacteriemia/microbiologia , Complicações do Diabetes/sangue , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
9.
J Enzyme Inhib Med Chem ; 34(1): 1388-1399, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31392901

RESUMO

Fourteen novel dipeptide carboxamide derivatives bearing benzensulphonamoyl propanamide were synthesized and characterized using 1H NMR, 13C NMR, FTIR and MS spectroscopic techniques. In vivo antimalarial and in vitro antimicrobial studies were carried out on these synthesized compounds. Molecular docking, haematological analysis, liver and kidney function tests were also evaluated to assess the effect of the compounds on the organs. At 200 mg/kg body weight, 7i inhibited the multiplication of the parasite by 81.38% on day 12 of post-treatment exposure. This was comparable to the 82.34% reduction with artemisinin. The minimum inhibitory concentration (MIC) in µM ranged from 0.03 to 2.34 with 7h having MIC of 0.03 µM against Plasmodium falciparium. The in vitro antibacterial activity of the compounds against some clinically isolated bacteria strains showed varied activities with some of the new compounds showing better activities against the bacteria and the fungi more than the reference drug ciprofloxacin and fluconazole.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Dipeptídeos/química , Dipeptídeos/farmacologia , Sulfonamidas/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antimaláricos/síntese química , Bactérias/efeitos dos fármacos , Dipeptídeos/síntese química , Fungos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Testes de Sensibilidade Parasitária , Plasmodium falciparum/efeitos dos fármacos , Ratos , Sulfonamidas/química
10.
Braz Oral Res ; 33: e075, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31432926

RESUMO

Resinous infiltrants are indicated in the treatment of incipient carious lesions, and further development of these materials may contribute to greater control of these lesions. The aim of this study was to analyze the physical and antibacterial properties of experimental infiltrants containing iodonium salt and chitosan. Nine experimental infiltrants were formulated by varying the concentration of the diphenyliodonium salt (DPI) at 0, 0.5 and 1 mol%; and chitosan at 0, 0.12 and 0.25 g%. The infiltrants contained the monomeric base of triethylene glycol dimethacrylate and bisphenol-A dimethacrylate ethoxylate in a 75 and 25% proportion by weight, respectively; 0.5 mol% camphorquinone and 1 mol% ethyl 4-dimethylaminobenzoate. The degree of conversion was evaluated using Fourier transformer infrared spectroscopy, and the flexural strength and elastic modulus using the three-point bending test. Sorption and solubility in water, and antibacterial analysis (minimum inhibitory concentration and minimum bactericidal concentration) were also analyzed. Data was analyzed statistically by two-way ANOVA and Tukey's test (p<0.05), with the exception of the antibacterial test, which was evaluated by visual inspection. In general, the infiltrant group containing 0.5% DPI and 0.12% chitosan showed high values of degree of conversion, higher values of elastic modulus and flexural strength, and lower sorption values in relation to the other groups. Antibacterial activity was observed in all the groups with DPI, regardless of the concentration of chitosan. The addition of DPI and chitosan to experimental infiltrants represents a valid option for producing infiltrants with desirable physical and antibacterial characteristics.


Assuntos
Antibacterianos/química , Quitosana/química , Resinas Compostas/química , Metacrilatos/química , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , Sais/química , Análise de Variância , Antibacterianos/farmacologia , Quitosana/farmacologia , Resinas Compostas/farmacologia , Módulo de Elasticidade , Resistência à Flexão , Lactobacillus acidophilus/efeitos dos fármacos , Cura Luminosa de Adesivos Dentários , Teste de Materiais , Metacrilatos/farmacologia , Testes de Sensibilidade Microbiana , Polietilenoglicóis/farmacologia , Ácidos Polimetacrílicos/farmacologia , Valores de Referência , Reprodutibilidade dos Testes , Sais/farmacologia , Solubilidade , Estatísticas não Paramétricas , Streptococcus mutans/efeitos dos fármacos
11.
An Acad Bras Cienc ; 91(3): e20180404, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365649

RESUMO

In this study, the antimicrobial, antioxidant and antitumor activity of ethanol extracts obtained from Phlomis russeliana (Sims.) Lag. ex Benth. (Lamiaceae) were evaluated. Disc diffusion and microdilution methods were used to test the extracts for antimicrobial activity against seven bacteria strains (Bacillus cereus ATCC 7064, Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6538P, Escherichia coli ATCC 10538, Proteus vulgaris ATCC 6899, Salmonella typhimurium CCM 5445 and Pseudomonas aeruginosa ATCC 27853) and four yeast strains (Kluyveromyces fragilis ATCC 8608, Rhodotorula rubra ATCC 70403, Debaryomyces hansenii DSM 70238 and Candida albicans ATCC 10239). Notably, they were more effective against the yeast strains than the bacterial strains. Of the yeast cultures, D. hanseii was among the most susceptible, having an inhibition zone of 16.2 mm with minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of 64(128)µg/ml, respectively. For cytotoxic determination, Caco-2 cells were cultured as per ATCC protocol, and were treated with log concentrations (5-80 mg/ml) of P. russeliana. The potency of cell growth inhibition for each extract was expressed as an IC50 value. Moreover, oxidant capacity was evaluated via TOC assay. This product induced antiproliferative activity of 31.33% at 40 mg/ml and 20.96% at 80 mg/ml, without toxic effects on cells, although the oxidant capacity was decreased to 27.06 ± 0.7 nm in the 80 mg/ml-applied group compared to 47.9 ± 1.8 nm in the untreated one. Advanced pharmacological studies are needed to further evaluate P. russeliana for distinctive features.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Candida albicans/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Phlomis/química , Extratos Vegetais/farmacologia , Antibacterianos/isolamento & purificação , Antioxidantes/isolamento & purificação , Células CACO-2 , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Bactérias Gram-Negativas/classificação , Bactérias Gram-Positivas/classificação , Humanos , Turquia
13.
An Acad Bras Cienc ; 91(3): e20180621, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31411258

RESUMO

Aristolochia triangularis Cham., is one of the most frequently used medicinal plant in Southern Brazil. Preparations containing the leaves and/or stems are traditionally used as anti-inflammatory, diuretic, as well as antidote against snakebites. This study screened A. triangularis extracts, fractions and isolated compounds for different bioactivities. A weak antiproliferative activity against human lung cancer cell line (A549) was observed only for chloroform fraction obtained from stems (CFstems - CC50: 2.93 µg/mL). Also, a moderate antimicrobial activity against Staphylococcus aureus was detected just for chloroform fraction obtained from leaves (CFleaves -13-16 mm inhibition zone). Additionally, two semi-purified fractions (CFstems-4 and CFleaves-4) selectively inhibited HSV-1 replication (IC50 values of 0.40 and 2.61 µg/mL, respectively), while only CFleaves showed promising results against Leishmania amazonensis. Fractionation of extracts resulted in the isolation of one neolignan (-) cubebin and one lignan (+) galbacin. However, these compounds are not responsible for the in vitro bioactivities herein detected. The presence of aristolochic acid I and aristolochic acid II in the crude ethanol extract of stems (CEEstems) and leaves (CEEleaves) was also investigated. The HPLC analysis of these extracts did not display any peak with retention time or UV spectra comparable to aristolochic acids I and II.


Assuntos
Aristolochia/química , Compostos Fitoquímicos/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antiprotozoários/farmacologia , Antivirais/farmacologia , Ácidos Aristolóquicos/química , Brasil , Fracionamento Químico , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
14.
J Enzyme Inhib Med Chem ; 34(1): 1414-1425, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401901

RESUMO

The emergence of drug-resistant pathogenic bacteria is occurring due to the global overuse and misuse of ß-lactam antibiotics. Infections caused by some bacteria which secrete metallo-ß-lactamases (enzymes that inactivate ß-lactam antibiotics) are increasingly prevalent and have become a major worldwide threat to human health. These bacteria are resistant to ß-lactam antibiotics and MBL-inhibitor/ß-lactam antibiotic combination therapy can be a strategy to overcome this problem. So far, no clinically available inhibitors of metallo-ß-lactamases (MBLs) have been reported. In this study, L-benzyl tyrosine thiol carboxylic acid analogues (2a-2k) were synthesized after the study of computational simulation by adding of methyl, chloro, bromo and nitro groups to the benzyl ring for investigation of SAR analysis. Although the synthesized molecules 2a-k shows the potent inhibitory effects against metallo-ß-lactamase (IMP-1) with the range of Kic values of 1.04-4.77 µM, they are not as potent as the candidate inhibitor.


Assuntos
Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Compostos de Sulfidrila/química , Tirosina/química , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Ácidos Carboxílicos/química , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/enzimologia , Relação Estrutura-Atividade , Inibidores de beta-Lactamases/química
16.
Epidemiol Mikrobiol Imunol ; 68(2): 75-81, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398980

RESUMO

AIM: The purpose of the surveillance performed from October to December in 2010-2017 was to monitor the trends in the susceptibility to beta-lactam and macrolide antibiotics in Streptococcus pneumoniae isolates from respiratory tract infections in the Czech Republic. MATERIAL AND METHODS: Between 42 and 55 laboratories participated in the study every year. Consecutive non-duplicate pneumococcal isolates from relevant microbiological specimens from patients with community-acquired bacterial respiratory tract infection were sequentially included in the study. Laboratories recorded qualitative results of penicillin and erythromycin susceptibility testing; susceptibility to antibiotics was determined by the disk diffusion method. Penicillin non-susceptible and/or erythromycin resistant isolates were referred to the National Reference Laboratory for Antibiotics, where the minimum inhibitory concentration of each antibiotic was tested using the broth microdilution method, and their serotyping was performed in the National Reference Laboratory for Streptococcal Infections. Twenty-six isolates from 2017 were analysed by the multilocus sequence typing method. RESULTS: In total, 7 491 pneumococcal strains were examined, of which 53.7% (4 023) were from the upper respiratory tract and 47.7% (3 573) from children under 15 years of age. Non-susceptibility to penicillin decreased from 2.6% in 2010 to 1.2% in 2017, while resistance to erythromycin increased from 7.4% to 9.7% over the same period. Penicillin non-susceptible isolates were mostly of serotypes 19A, 19F, and 15A. Macrolide resistant but penicillin susceptible isolates were predominantly represented by serotypes 19A and 3. The presence of the Taiwan19F-14 clone was confirmed in penicillin non-susceptible isolates by MLST, and the most frequently identified sequence type (ST) in macrolide resistant isolates was ST416 classified into the Netherlands15B-37 clone. CONCLUSIONS: The respiratory study of antibiotic resistance in S. pneumoniae confirmed the decreasing trend of resistance to penicillin but revealed a growing resistance to macrolide antibiotics in the Czech Republic. The results of our study confirm that antibiotic resistance in the vaccination era is associated primarily with the non-vaccine serotypes, and the clonal expansion of macrolide resistant serotype 19A was apparently supported by the growing prescription of macrolide antibiotics.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Infecções Pneumocócicas , Streptococcus pneumoniae , Adolescente , Antibacterianos/farmacologia , Criança , República Tcheca/epidemiologia , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Sorotipagem , Streptococcus pneumoniae/efeitos dos fármacos
17.
Epidemiol Mikrobiol Imunol ; 68(2): 99-102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398983

RESUMO

The increasing incidence of multiresistant bacterial strains is currently a serious health concern. These pathogens are often the cause of nosocomial infections with limited treatment options and high fatality rates. A case report is presented of an uncommon detection of four different species (Citrobacter freundii, Klebsiella pneumoniae, Escherichia coli, and Morganella morganii) producing the same type of carbapenemase, KPC-2, in a female patient during her complicated long-term hospital stay. Resistance was probably spread to other species by horizontal transmission of plasmids carrying the blaKPC-2 genes. The implementation of strict anti-epidemic measures prevented further spread of these carbapenem-resistant bacteria.


Assuntos
Antibacterianos , Bactérias , Infecções Bacterianas , Infecção Hospitalar , beta-Lactamases , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Infecções Bacterianas/microbiologia , Proteínas de Bactérias/genética , Coinfecção/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana/genética , Feminino , Transferência Genética Horizontal , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , beta-Lactamases/genética
18.
Chem Commun (Camb) ; 55(69): 10192-10213, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31411602

RESUMO

Light is unsurpassed in its ability to modulate biological interactions. Since their discovery, chemists have been fascinated by photosensitive molecules capable of switching between isomeric forms, known as photoswitches. Photoswitchable peptides have been recognized for many years; however, their functional implementation in biological systems has only recently been achieved. Peptides are now acknowledged as excellent protein-protein interaction modulators and have been important in the emergence of photopharmacology. In this review, we briefly explain the different classes of photoswitches and summarize structural studies when they are incorporated into peptides. Importantly, we provide a detailed overview of the rapidly increasing number of examples, where biological modulation is driven by the structural changes. Furthermore, we discuss some of the remaining challenges faced in this field. These exciting proof-of-principle studies highlight the tremendous potential of photocontrollable peptides as optochemical tools for chemical biology and biomedicine.


Assuntos
Descoberta de Drogas , Peptídeos/química , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Morte Celular/efeitos dos fármacos , Descoberta de Drogas/métodos , Humanos , Isomerismo , Luz , Modelos Moleculares , Ácidos Nucleicos/metabolismo , Peptídeos/metabolismo , Processos Fotoquímicos , Mapas de Interação de Proteínas/efeitos dos fármacos
19.
Klin Mikrobiol Infekc Lek ; 25(1): 4-6, 2019 Mar.
Artigo em Tcheco | MEDLINE | ID: mdl-31266086

RESUMO

The emergence of plasmid-mediated colistin resistance carried by mcr genes and polymyxin resistance in carbapenem-resistant bacteria poses a threat to antibiotic therapy of bacterial infections. The worldwide spread of colistin resistance carried by mcr genes, particularly in Enterobacteriaceae, points to the possibility of the spread of this type of resistance also in non-fermenting Gram-negative bacteria such as Pseudomonas aeruginosa or Acinetobacter baumannii. This study provides information on the first described occurrence of the mcr-4 gene in A. baumannii isolated from imported turkey liver obtained in the retail market of the Czech Republic.


Assuntos
Acinetobacter baumannii , Colistina , Farmacorresistência Bacteriana , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Colistina/farmacologia , República Tcheca , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana
20.
J Photochem Photobiol B ; 197: 111541, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31272033

RESUMO

Here, we report the novel fabrication of ZnO nanoparticles using the Costus igneus leaf extract. Gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy to determine the bioactive components present in the plant extract. The synthesis of Ci-ZnO NPs (C. igneus- coated zinc oxide nanoparticles) was accomplished using a cost-effective and simple technique. Ci-ZnO NPs were specified using UV-visible spectroscopy, FTIR, XRD, and TEM. Ci-ZnO NPs was authenticated by UV-Vis and exhibited a peak at 365 nm. The XRD spectra proved the crystalline character of the Ci-ZnO NPs synthesized as hexagonal wurtzite. The FTIR spectrum illustrated the presence of possible functional groups present in Ci-ZnO NPs. The TEM micrograph showed evidence of the presence of a hexagonal organization with a size of 26.55 nm typical of Ci-ZnO NPs. The α-amylase and α-glucosidase inhibition assays demonstrated antidiabetic activity of Ci-ZnO NPs (74 % and 82 %, respectively), and the DPPH [2,2-diphenyl-1-picrylhydrazyl hydrate] assay demonstrated the antioxidant activity of the nanoparticles (75%) at a concentration of 100 µg/ml. The Ci-ZnO NPs exhibited promising antibacterial and biofilm inhibition activity against the pathogenic bacteria Streptococcus mutans, Lysinibacillus fusiformis, Proteus vulgaris, and Vibrio parahaemolyticus. Additionally, the Ci-ZnO NPs showed biocompatibility with mammalian RBCs with minimum hemolytic activity (0.633 % ±â€¯0.005 %) at a concentration of 200 µg/ml.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/química , Biofilmes/efeitos dos fármacos , Nanopartículas Metálicas/química , Extratos Vegetais/química , Óxido de Zinco/química , Antibacterianos/síntese química , Antibacterianos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Costus/química , Costus/metabolismo , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/fisiologia , Química Verde , Hemólise/efeitos dos fármacos , Humanos , Insulina/química , Nanopartículas Metálicas/toxicidade , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Extratos Vegetais/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo
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