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1.
BMC Microbiol ; 24(1): 202, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851699

RESUMO

BACKGROUND: Bacteroides fragilis group (BFG) species are the most significant anaerobic pathogens and are also the most antibiotic-resistant anaerobic species. Therefore, surveying their antimicrobial resistance levels and investigating their antibiotic resistance mechanisms is recommended. Since their infections are endogenous and they are important constituents of the intestinal microbiota, the properties of the intestinal strains are also important to follow. The aim of this study was to investigate the main antibiotic gene content of microbiota isolates from healthy people and compare them with the gene carriage of strains isolated from infections. RESULTS: We detected 13, mainly antibiotic resistance determinants of 184 intestinal BFG strains that were isolated in 5 European countries (Belgium, Germany, Hungary, Slovenia and Turkey) and compared these with values obtained earlier for European clinical strains. Differences were found between the values of this study and an earlier one for antibiotic resistance genes that are considered to be mobile, with higher degrees for cfxA, erm(F) and tet(Q) and with lower degrees for msrSA, erm(B) and erm(G). In addition, a different gene prevalence was found depending on the taxonomical groups, e.g., B. fragilis and NBFB. Some strains with both the cepA and cfiA ß-lactamase genes were also detected, which is thought to be exceptional since until now, the B. fragilis genetic divisions were defined by the mutual exclusion of these two genes. CONCLUSIONS: Our study detected the prevalences of a series of antibiotic resistance genes in intestinal Bacteroides strains which is a novelty. In addition, based on the current and some previous data we hypothesized that prevalence of some antibiotic resistance genes detected in the clinical and intestinal BFG strains were different, which could be accounted with the differential composition of the Bacteroides microbiota and/or the MGE mobilities at the luminal vs. mucosal sites of the intestine.


Assuntos
Antibacterianos , Infecções por Bacteroides , Bacteroides , Carbapenêmicos , Humanos , Europa (Continente) , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Infecções por Bacteroides/microbiologia , Bacteroides/genética , Bacteroides/efeitos dos fármacos , Bacteroides/isolamento & purificação , Farmacorresistência Bacteriana/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Testes de Sensibilidade Microbiana , Genes Bacterianos/genética , Intestinos/microbiologia , Proteínas de Bactérias/genética
2.
Int J Mol Sci ; 25(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38732202

RESUMO

Acquiring resistance against antiviral drugs is a significant problem in antimicrobial therapy. In order to identify novel antiviral compounds, the antiviral activity of eight plants indigenous to the southern region of Hungary against herpes simplex virus-2 (HSV-2) was investigated. The plant extracts and the plant compound carnosic acid were tested for their effectiveness on both the extracellular and intracellular forms of HSV-2 on Vero and HeLa cells. HSV-2 replication was measured by a direct quantitative PCR (qPCR). Among the tested plant extracts, Salvia rosmarinus (S. rosmarinus) exhibited a 90.46% reduction in HSV-2 replication at the 0.47 µg/mL concentration. Carnosic acid, a major antimicrobial compound found in rosemary, also demonstrated a significant dose-dependent inhibition of both extracellular and intracellular forms of HSV-2. The 90% inhibitory concentration (IC90) of carnosic acid was between 25 and 6.25 µg/mL. Proteomics and high-resolution respirometry showed that carnosic acid suppressed key ATP synthesis pathways such as glycolysis, citrate cycle, and oxidative phosphorylation. Inhibition of oxidative phosphorylation also suppressed HSV-2 replication up to 39.94-fold. These results indicate that the antiviral action of carnosic acid includes the inhibition of ATP generation by suppressing key energy production pathways. Carnosic acid holds promise as a potential novel antiviral agent against HSV-2.


Assuntos
Abietanos , Trifosfato de Adenosina , Antivirais , Herpesvirus Humano 2 , Extratos Vegetais , Replicação Viral , Abietanos/farmacologia , Replicação Viral/efeitos dos fármacos , Chlorocebus aethiops , Células Vero , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/biossíntese , Humanos , Animais , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/fisiologia , Antivirais/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células HeLa
3.
BMC Pediatr ; 23(1): 301, 2023 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-37328771

RESUMO

BACKGROUND: The incidence of tonsillopharyngitis is especially prevalent in children. Despite the fact that viruses cause the majority of infections, antibiotics are frequently used as a treatment, contrary to international guidelines. This is not only an inappropriate method of treatment for viral infections, but it also significantly contributes to the emergence of antibiotic-resistant strains. In this study, EBV and CMV-related tonsillopharyngitis were distinguished from other pathogens by using machine learning techniques to construct a classification tree based on clinical characteristics. MATERIALS AND METHODS: In 2016 and 2017, we assessed information regarding 242 children with tonsillopharyngitis. Patients were categorized according to whether acute cytomegalovirus or Epstein-Barr virus infections were confirmed (n = 91) or not (n = 151). Based on symptoms and blood test parameters, we constructed decision trees to discriminate the two groups. The classification efficiency of the model was characterized by its sensitivity, specificity, positive predictive value, and negative predictive value. Fisher's exact and Welch's tests were used to perform univariable statistical analyses. RESULTS: The best decision tree distinguished EBV/CMV infection from non-EBV/CMV group with 83.33% positive predictive value, 88.90% sensitivity and 90.30% specificity. GPT (U/l) was found to be the most discriminatory variable (p < 0.0001). Using the model, unnecessary antibiotic treatment could be reduced by 66.66% (p = 0.0002). DISCUSSION: Our classification model can be used as a diagnostic decision support tool to distinguish EBC/CMV infection from non EBV/CMV tonsillopharyngitis, thereby significantly reducing the overuse of antibiotics. It is hoped that the model may become a tool worth considering in routine clinical practice and may be developed to differentiate between viral and bacterial infections.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Faringite , Humanos , Criança , Infecções por Vírus Epstein-Barr/diagnóstico , Antibacterianos/uso terapêutico , Herpesvirus Humano 4 , Faringite/diagnóstico , Faringite/tratamento farmacológico , Árvores de Decisões
4.
Cent Eur J Public Health ; 31(3): 166-170, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37934479

RESUMO

OBJECTIVES: Hepatitis E virus (HEV) has recently become endemic in Europe, however, it is often a remnant neglected by clinicians as the causative agent of acute and chronic hepatitis and is often misdiagnosed as a drug-induced liver injury. The infection rate in European pig farms is estimated to be around 15-20%, therefore, the primary source of HEV infections might be poorly prepared pork meat. As HEV infections may occur more often in clinical practice than previously thought, the present paper aims to analyse the seroprevalence of HEV in patients with acute hepatitis over a period of 14 years in Csongrád County, Hungary. METHODS: The sera of 4,270 hepatitis patients collected between 2004-2018 were tested for cumulative anti-HEV IgG/IgM. Furthermore, 170 IgM positive sera were tested for the presence of viral RNA by RT-qPCR. RESULTS: Between 2012-2018, the cumulative seroprevalence has increased 9.18 times, and between 2013-2018, IgM prevalence has increased 12.49 times. Viral RNA was detectable in 12.35% of IgM positive sera. CONCLUSION: The present paper presents data showing that the seroprevalence of hepatitis E virus has increased markedly over the course of the last decade in Hungary and in other European countries as well. The exact reason behind this phenomenon is yet to be determined. To assess the dynamics and the reason for this increase in prevalence, pan-European, multicentre studies should be conducted.


Assuntos
Vírus da Hepatite E , Hepatite E , Humanos , Animais , Suínos , Hungria , Estudos Soroepidemiológicos , RNA Viral , Imunoglobulina M
5.
Emerg Infect Dis ; 28(12): 2559-2561, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36418009

RESUMO

Ocular infections with Thelazia callipaeda eyeworms in Europe have become more common. We report a case in Hungary caused by T. callipaeda eyeworms in a 45-year-old woman who had no travel history abroad.


Assuntos
Doenças do Cão , Infecções por Spirurida , Thelazioidea , Cães , Animais , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Spirurida/diagnóstico , Hungria , Loa
6.
J Antimicrob Chemother ; 77(6): 1553-1556, 2022 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-35296904

RESUMO

OBJECTIVES: We sought to characterize the carbapenem resistance mechanism of Bacteroides xylanisolvens 14880, an imipenem-resistant strain from Germany, and assess its prevalence. METHODS: Antimicrobial susceptibilities were determined using agar dilution or Etest methodology and specific imipenemase activity was detected. The genomic sequence of B. xylanisolvens 14880 was determined and analysed for antibiotic resistance genes and genomic islands. We also used gene transfer to a carbapenem susceptible host, along with 5'-RACE, conventional PCR with capillary sequencing and RT-PCR-based screening. RESULTS: B. xylanisolvens 14880 displayed resistance to carbapenems and produced high specific imipenemase activity. Its genomic sequence was 6.1 Mbp and a class B1 ß-lactamase gene (termed crxA) was detected in it. crxA was carried on a putative genomic island with insertion sequence (IS) elements and a putative GNAT (Gcn5-like acetyltransferase) toxin gene. Promoter localization by 5'-RACE and gene targeting to an imipenem-susceptible Bacteroides host indicated that it is activated by an IS1380-like IS element and it can confer carbapenem resistance. The PCR screening of Bacteroides strains showed that crxA was specific to B. xylanisolvens with a carriage rate of 16.7%. CONCLUSIONS: B. xylanisolvens strains can harbour a carbapenem resistance gene, which has many similarities to the 'cfiA system': metallo-ß-lactamase (MBL), IS element activation, carriage of a GNAT toxin gene, specific for a unique Bacteroides species with a significant prevalence.


Assuntos
Elementos de DNA Transponíveis , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Bacteroides/genética , Bacteroides/metabolismo , Bacteroides fragilis/genética , Carbapenêmicos/farmacologia , Genômica , Imipenem , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , beta-Lactamases/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-35084364

RESUMO

The acronym ESKAPE stands for six antibiotic-resistant bacterial pathogens namely, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Monitoring their resistance is an important task for clinical microbiology laboratories. Our aim was to analyze the resistance patterns of these bacteria over ten years in clinical samples of our department. We examined the sample types from which these pathogens were most frequently isolated. The incidence of tests with resistant results for each pathogen in aggregate and the most important subgroups of each was also analyzed. We have also intended to predict the local priorities amongst these pathogens. The results of 1,268,126 antibiotic susceptibility tests performed on a total of 70,099 isolates over this period were examined. Most strains were derived from urine, blood culture, trachea, vagina, wounds, and abscesses. Prevalence of ESKAPE bacteria increased between 2011 and 2020 however, the steepest intensifications were seen in the cases of K. pneumoniae and P. aeruginosa. The number of antibiotic susceptibility tests with resistant results has also increased over the decade but the most notable increase was detected in E. faecium and A. baumannii. Based on the calculation of antimicrobial resistance index for each pathogen, the most serious challenges for us at present are A. baumannii, P. aeruginosa, and E. faecium and their multi-resistant forms. The theoretical prediction of proportion of resistant tests between 2020 and 2030 in our care area draws attention to a worrying trend in the cases of vancomycin-resistant E. faecium and carbapenem-resistant A. baumannii strains.

8.
Anaerobe ; 73: 102480, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34800619

RESUMO

The antimicrobial susceptibilities of Bacteroides strains isolated from the feces of imipenem-treated patients from Belgium and Hungary were compared with those isolated from the normal microbiota from these two and five other European countries and assessed. Of the 10 antibiotics tested, highly significant differences were found with cefoxitin (decrease for Belgium and for this two and the five countries from the previous study), clindamycin (decrease for Belgium and for this two and the five countries from the previous study) and moxifloxacin (increase for Belgium and for this two and the five countries from the previous study) relative to normal microbiota strains reported earlier. Imipenem treatment brought about modest, but notable differences in the compositions of the microbiomes where there was less diversity in the treated group relative to the non-treated group.


Assuntos
Infecções por Bacteroides , Microbioma Gastrointestinal , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteroides , Infecções por Bacteroides/tratamento farmacológico , Infecções por Bacteroides/epidemiologia , Bacteroides fragilis , Bélgica/epidemiologia , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana , Fezes , Humanos , Hungria/epidemiologia , Testes de Sensibilidade Microbiana
9.
Acta Derm Venereol ; 101(1): adv00369, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33241420

RESUMO

Human epidermal keratinocytes sense the presence of human skin microbiota through pathogen recognition receptors, such as toll-like receptors, and induce innate immune and inflammatory events. In healthy epidermis there is an absence of inflammation despite the continuous presence of cutaneous microbes, which is evidence of an effective immune regulatory mechanism. The aim of this study was to investigate tumour necrosis factor alpha-induced protein 3 (TNFAIP3), a negative regulator of toll-like receptor and nuclear factor kappa B signalling pathways, and its role in these regulatory events. A broad spectrum of toll-like receptor ligands induced TNFAIP3 expression, as did live Cutibacterium acnes, which is involved in the pathogenesis of acne. Changes in bacterium-induced, dose-dependent TNFAIP3 expression were Jun kinase- and nuclear factor kappa B-dependent, and resulted in altered cytokine and chemokine levels in in vitro cultured human keratinocytes. In acne lesions, TNFAIP3 mRNA expression was elevated compared with non-lesional skin samples from the same individuals. These results suggest that TNFAIP3 may have a general role in fine regulation of microbiota-induced cutaneous immune homeostasis.


Assuntos
Acne Vulgar , Receptor 2 Toll-Like , Células Cultivadas , Epiderme , Humanos , Imunidade Inata , Queratinócitos , Propionibacterium acnes , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-34524972

RESUMO

Bacteria can enhance their survival by attaching to inanimate surfaces or tissues, and presenting as multicellular communities encased in a protective extracellular matrix called biofilm. There has been pronounced interest in assessing the relationship between the antibiotic resistant phenotype and biofilm-production in clinically-relevant pathogens. The aim of the present paper was to provide additional experimental results on the topic, testing the biofilm-forming capacity of Escherichia coli isolates using in vitro methods in the context of their antibiotic resistance in the form of a laboratory case study, in addition to provide a comprehensive review of the subject. In our case study, a total of two hundred and fifty (n = 250) E. coli isolates, originating from either clean-catch urine samples (n = 125) or invasive samples (n = 125) were included. The colony morphology of isolates were recorded after 24h, while antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Biofilm-formation of the isolates was assessed with the crystal violet tube-adherence method. Altogether 57 isolates (22.8%) isolates were multidrug resistant (MDR), 89 isolates (35.6%) produced large colonies (>3 mm), mucoid variant colonies were produced in 131 cases (52.4%), and 108 (43.2%) were positive for biofilm formation. Biofilm-producers were less common among isolates resistant to third-generation cephalosporins and trimethoprim-sulfamethoxazole (P = 0.043 and P = 0.023, respectively). Biofilms facilitate a protective growth strategy in bacteria, ensuring safety against environmental stressors, components of the immune system and noxious chemical agents. Being an integral part of bacterial physiology, biofilm-formation is interdependent with the expression of other virulence factors (especially adhesins) and quorum sensing signal molecules. More research is required to allow for the full understanding of the interplay between the MDR phenotype and biofilm-production, which will facilitate the development of novel therapeutic strategies.

11.
Anaerobe ; 69: 102357, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33713801

RESUMO

Eleven metronidazole resistant Bacteroides and one newly classified Phocaeicola dorei strain from Kuwait were investigated for their resistance mechanisms and the emergence of their resistant plasmids. All but one strain harbored nimE genes on differently sized plasmids. Of the 11 nimE genes, 9 were preceded by full copies of the prototype ISBf6 insertion sequence element, one carried a truncated ISBf6 and one was activated by an additional copy of IS612B. Nucleotide sequencing results showed that the nimE ISBf6 distances were constant and all five different plasmids shared a common region, suggesting that (i) the nimE-ISBf6 configuration was inserted into an undisclosed common genetic element, (ii) over time, this common element was mutated by insertions and deletions, spreading the resultant plasmids. Of the 10 B. fragilis strains in this collection, 6 were also cfiA-positive, one with full imipenem resistance, indicating a tendency for multidrug resistance (MDR) among such isolates. The significant number of metronidazole resistant Bacteroides spp. and P. dorei strains with the MDR phenotype warns of difficulties in treatment and suggests promoting adherence to antibiotic stewardship recommendations in Kuwait.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bacteroides/tratamento farmacológico , Bacteroides/efeitos dos fármacos , Bacteroides/genética , Farmacorresistência Bacteriana/genética , Metronidazol/uso terapêutico , Variação Genética , Genótipo , Humanos , Kuweit , Testes de Sensibilidade Microbiana
12.
Acta Microbiol Immunol Hung ; 67(4): 209-215, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258795

RESUMO

Infections caused by carbapenem-resistant Enterobacterales (CRE) present an important therapeutic problem, as there are limited number of effective therapeutic alternatives available. In this study, phenotypic and genotypic methods were used to characterize carbapenemase-production and other resistance-determinants (AmpC and ESBL-production, efflux pump-overexpression) in 50 isolates (Klebsiella spp. n = 35, Escherichia coli n = 12 and Enterobacter cloacae complex n = 3) collected at the Albert Szent-Györgyi Clinical Center (University of Szeged) between 2014 and 2017. Minimum inhibitory concentrations of meropenem, sulfamethoxazole/trimethoprim, tigecycline, amikacin, moxifloxacin, colistin and fosfomycin were also determined. 24% of isolates were AmpC-producers, while 30% carried blaCTX-M ESBL-genes. Carbapenemase-genes were detected in 18 (36%) of the tested isolates: in 2 isolates blaNDM, in 6 isolates blaOXA-48-like and in 12 isolates, blaVIM was detected by PCR. The species-distribution for isolates positive for carbapenemase-genes was the following: Klebsiella pneumoniae n = 11, Klebsiella oxytoca n = 1, E. coli n = 5, E. cloacae complex n = 1. Efflux pump-overexpression based on the PAßN-screening agar was shown in n = 3 of the tested strains. In nine isolates (18%), carbapenemase and ESBL-genes were detected simultaneously. Highest levels of resistance were noted for fosfomycin (74%) and moxifloxacin (70%), while all isolates were susceptible to colistin. Among applied phenotypic tests in this study the modified carbapenem inactivation method (mCIM) proved to be the most accurate one compared to that of PCR results.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , beta-Lactamases/biossíntese , beta-Lactamases/genética , Proteínas de Bactérias/classificação , Enterobacteriaceae/classificação , Enterobacteriaceae/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Proteínas de Escherichia coli/biossíntese , Proteínas de Escherichia coli/genética , Humanos , Hungria , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Testes de Sensibilidade Microbiana , beta-Lactamases/classificação
13.
Artigo em Inglês | MEDLINE | ID: mdl-30373805

RESUMO

The transmission of the urogenital serovars of Chlamydia trachomatis can be significantly influenced by vaginal gels. Hydroxyethyl cellulose is a commonly used gelling agent that can be found in vaginal gels. Hydroxyethyl cellulose showed a concentration-dependent growth-enhancing effect on C. trachomatis serovars D and E, with a 26.1-fold maximal increase in vitro and a 2.57-fold increase in vivo.


Assuntos
Celulose/análogos & derivados , Chlamydia trachomatis/efeitos dos fármacos , Vagina/efeitos dos fármacos , Cremes, Espumas e Géis Vaginais/química , Animais , Celulose/farmacologia , Chlamydia trachomatis/classificação , Chlamydia trachomatis/crescimento & desenvolvimento , Chlamydia trachomatis/patogenicidade , Contagem de Colônia Microbiana , Meios de Cultura/química , Meios de Cultura/farmacologia , Feminino , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Sorogrupo , Vagina/microbiologia , Virulência/efeitos dos fármacos
14.
Medicina (Kaunas) ; 55(7)2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324035

RESUMO

Background and Objective: Urinary tract infections (UTIs) are common in human medicine, affecting large patient populations worldwide. The principal cause of UTIs is uropathogenic Escherichia coli (UPEC) and Klebsiella, both in community and nosocomial settings. The assessment of local data on prevalence and resistance is essential to evaluate trends over time and to reflect on the national situation, compared to international data, using the methods of analytical epidemiology. Materials and Methods: The aim of this study was to assess resistance trends and epidemiology of UTIs caused by E. coli and Klebsiella species in inpatients and outpatients at a tertiary-care hospital in Hungary, using microbiological data. To evaluate resistance trends, several antibiotics were chosen as indicator drugs, based on local utilization data. Results: E. coli was the most prevalent isolate, representing 56.75 ± 4.86% for outpatients and 42.29 ± 2.94% for inpatients. For E. coli, the ratio of resistant strains for several antibiotics was significantly higher in the inpatient group, while in Klebsiella, similar trends were only observed for gentamicin. Extended-spectrum ß-lactamase (ESBL)-producing isolates were detected in 4.33-9.15% and 23.22-34.22% from outpatient, 8.85-38.97% and 10.89-36.06% from inpatient samples for E. coli and Klebsiella, respectively. Conclusions: Resistance developments in common UTI pathogens (especially to fosfomycin, sulfamethoxazole-trimethoprim, fluoroquinolones, and 3rd generation cephalosporins), seriously curb therapeutic options, especially in outpatient settings.


Assuntos
Farmacorresistência Bacteriana , Infecções Urinárias/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Feminino , Humanos , Hungria/epidemiologia , Lactente , Klebsiella/efeitos dos fármacos , Klebsiella/patogenicidade , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Prevalência , Estudos Retrospectivos , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/estatística & dados numéricos , Infecções Urinárias/epidemiologia , beta-Lactamases/uso terapêutico
15.
Planta Med ; 84(9-10): 729-735, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29554708

RESUMO

A novel segetane (1: ) and jatrophane diterpene (2: ), together with five known diterpenoids possessing segetane (3: ), jatrophane (4: ), and ingenane skeletons (5 - 7: ), were isolated from the methanol extract of Euphorbia taurinensis All. The structure elucidation of the compounds was performed by means of extensive spectroscopic analysis, including HRESIMS and 1D (1H, J-modulated spin-echo carbon experiment) and 2D (HSQC, HMBC, COSY, NOESY) NMR experiments. The multidrug resistance reversing and cytotoxic effects of five diterpenes (1, 4:  - 7: ) were studied on the L5178 mouse lymphoma cell line using rhodamine 123 accumulation and the MTT cell viability assay. Segetane and jatrophane diterpenes had no cytotoxic activity on the sensitive parent and multidrug resistance cells, while ingenane diterpenes showed a cytotoxic effect on both cell lines. Ingenanes 6: and 7: and segetane 1: demonstrated the remarkable multidrug resistance modulating effect at 20 µM.


Assuntos
Diterpenos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Euphorbia/química , Animais , Linhagem Celular Tumoral , Diterpenos/efeitos adversos , Diterpenos/química , Diterpenos/isolamento & purificação , Resistência a Múltiplos Medicamentos , Camundongos , Estrutura Molecular
16.
Molecules ; 23(8)2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127296

RESUMO

Juncaceae species are rich sources of phenanthrenes. The present study has focused on the isolation and structure determination of biologically active components from Juncus compressus. Eleven compounds (nine phenanthrenes and two flavonoids) have been isolated from the plant by the combination of different chromatographic methods. Two compounds (compressins A (Compound 1) and B (Compound 2)) are novel natural products, while seven phenanthrenes (effusol (Compound 3), effususol (Compound 4), juncusol (Compound 5), 2-hydroxy-1-methyl-4-oxymethylene-5-vinyl-9,10-dihydrophenanthrene (Compound 6), 7-hydroxy-1-methyl-2-methoxy-5-vinyl-9,10-dihydrophenanthrene (Compound 7), effususin A (Compound 8), and dehydroeffusol (Compound 9)), and two flavonoids (apigenin (Compound 10) and luteolin (Compound 11) were isolated for the first time from the plant. Compressin B (Compound 2) is a dimeric phenanthrene, in which two juncusol monomers (Compound 5) are connecting through their C-3 atoms. The structure elucidation of the isolated compounds was carried out using 1D, 2D NMR spectroscopic methods and HR-MS measurements. In vitro investigation of the antiproliferative effect of the phenanthrenes on two cervical (HeLa and SiHa) and an ovarian human tumor cell line (A2780) revealed that compounds have remarkable antiproliferative activity, mainly on the HeLa cell line. Moreover, juncusol (Compound 5) proved to possess significant antiviral activity against the herpes simplex 2 virus (HSV-2).


Assuntos
Antineoplásicos Fitogênicos/química , Antivirais/química , Proliferação de Células/efeitos dos fármacos , Magnoliopsida/química , Fenantrenos/química , Extratos Vegetais/química , Simplexvirus/efeitos dos fármacos , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antivirais/isolamento & purificação , Antivirais/farmacologia , Linhagem Celular Tumoral , Dimerização , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Fenantrenos/isolamento & purificação , Fenantrenos/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade
17.
Antimicrob Agents Chemother ; 58(1): 405-13, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24189259

RESUMO

Chlamydiae are obligate intracellular bacteria that propagate in the inclusion, a specific niche inside the host cell. The standard method for counting chlamydiae is immunofluorescent staining and manual counting of chlamydial inclusions. High- or medium-throughput estimation of the reduction in chlamydial inclusions should be the basis of testing antichlamydial compounds and other drugs that positively or negatively influence chlamydial growth, yet low-throughput manual counting is the common approach. To overcome the time-consuming and subjective manual counting, we developed an automatic inclusion-counting system based on a commercially available DNA chip scanner. Fluorescently labeled inclusions are detected by the scanner, and the image is processed by ChlamyCount, a custom plug-in of the ImageJ software environment. ChlamyCount was able to measure the inclusion counts over a 1-log-unit dynamic range with a high correlation to the theoretical counts. ChlamyCount was capable of accurately determining the MICs of the novel antimicrobial compound PCC00213 and the already known antichlamydial antibiotics moxifloxacin and tetracycline. ChlamyCount was also able to measure the chlamydial growth-altering effect of drugs that influence host-bacterium interaction, such as gamma interferon, DEAE-dextran, and cycloheximide. ChlamyCount is an easily adaptable system for testing antichlamydial antimicrobials and other compounds that influence Chlamydia-host interactions.


Assuntos
Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/isolamento & purificação , Corpos de Inclusão/microbiologia , Testes de Sensibilidade Microbiana , Análise de Sequência com Séries de Oligonucleotídeos
18.
Int J Med Microbiol ; 304(3-4): 476-83, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24631212

RESUMO

Chlamydia muridarum carries a cryptic plasmid (pMoPn) of 7.5kb, which encodes seven genes. Our aims were to describe the transcriptional pattern of the pMoPn genes in C. muridarum-infected mice and to evaluate the host immune responses against pGP3 and pGP4 proteins. BALB/c and C57BL/6N female mice were inoculated intranasally with C. muridarum and sacrificed at different time points, and the total RNA was extracted from the lung suspensions to determine the levels of expression of the different plasmid genes by RT qPCR. The supernatants of the lungs were subjected to the quantitation of recoverable C. muridarum. TCA04 and TCA05, which encode pGP3 and pGP4, respectively, were amplified by PCR and cloned into the pET vector. The proteins were overexpressed in E. coli HB101 and purified. Selected groups of BALB/c and C57BL/6N mice were infected with C. muridarum 1-3 times. The humoral immune responses in the sera of the mice to the proteins encoded by TCA04 and TCA05 were tested by Western blotting, and the cellular immune responses were assessed in lymphocyte proliferation assays. The proteins recognized by the mouse sera were further analysed by a LC/MSMS technique. The kinetics of C. muridarum growth were similar in the mouse strains used, but the pathogen burden was higher in the BALB/c mice in the late phase of infection. All the plasmid genes in the BALB/c mice showed an increased level of expression on day 7, whereas the expression of the same genes did not change on day 7 in the C57BL/6N mice. The levels of expression of the plasmid genes were higher in the C57BL/6N mice at later time points. In Western blot assays, the sera of the singly infected C57BL/6N mice reacted with the monomeric form of pGP3, whereas the sera of the singly infected BALB/c mice reacted with the trimeric form of pGP3. The sera of the multiply infected C57BL/6N mice also recognized pGP4. Similarly to the humoral immune response, cellular immune responses to pGP3 and pGP4 were detected in the C. muridarum-infected C57BL/6N mice, but the spleen cells of BALB/c mice responded with proliferation only to the pGP3 protein. These results suggest that the proteins encoded by pMoPn genes may modulate the host immune response during C. muridarum infection, and that the evolved immune response against plasmid proteins, similarly to that against other chlamydial proteins, depends on the genetic background of the host.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Chlamydia muridarum/imunologia , Plasmídeos , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/biossíntese , Proteínas de Bactérias/biossíntese , Western Blotting , Proliferação de Células , Chlamydia muridarum/genética , Cromatografia Líquida , Clonagem Molecular , Escherichia coli/genética , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Leucócitos Mononucleares/imunologia , Pulmão/microbiologia , Espectrometria de Massas , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
J Infect Public Health ; 17(7): 102453, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38820897

RESUMO

BACKGROUND: The presence of bacterial and fungal coinfections plays an important role in the mortality of patients with coronavirus 2019 (COVID-19). We compared data from the 3 years before and 3 years after the COVID-19 pandemic outbreak to evaluate its effect on the traits of bacterial and fungal diseases. METHODS: We retrospectively collected and analyzed data on positive respiratory tract samples (n = 13,133 samples from 7717 patients) and blood cultures (n = 23,652 from 9653 patients) between 2017 and 2022 from the Clinical Center of the University of Szeged, Hungary. We also evaluated antimicrobial susceptibility test results derived from 169,020 respiratory samples and 549,729 blood cultures to gain insight into changes in antimicrobial resistance. RESULTS: The most common respiratory pathogen in the pre-COVID era was Pseudomonas aeruginosa, whereas Candida albicans was the most frequent during the pandemic. The number of respiratory isolates of Acinetobacter baumannii was also markedly increased. In blood cultures, Staphylococcus epidermidis, Escherichia coli, and S. aureus were dominant during the study period, and A. baumannii was widespread in blood cultures during the pandemic years. Resistance to ofloxacin, penicillin, piperacillin-tazobactam, ceftazidime, cefepime, imipenem, ceftolozane-tazobactam, and itraconazole increased significantly in the COVID era. CONCLUSIONS: During the COVID-19 pandemic, there were changes in the prevalence of respiratory and blood culture pathogens at the Clinical Center of the University of Szeged. C. albicans became the predominant respiratory pathogen, and the number of A. baumannii isolates increased dramatically. Additionally, antimicrobial resistance notably increased during this period.


Assuntos
COVID-19 , Centros de Atenção Terciária , Humanos , COVID-19/epidemiologia , Hungria/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Coinfecção/microbiologia , Coinfecção/epidemiologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Micoses/epidemiologia , Micoses/microbiologia , Micoses/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificação , Infecções Respiratórias/microbiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/tratamento farmacológico , Farmacorresistência Bacteriana
20.
Vaccines (Basel) ; 12(2)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38400196

RESUMO

Chronic obstructive pulmonary disease (COPD) is a frequent, often progressive, chronic disease of the lungs. Patients with COPD often have impaired immunity; therefore, they are prone to chest infections, such as pneumonia or bronchitis. Acute exacerbations of COPD are major events that accelerate disease progression, contributing to its symptoms' burden, morbidity, and mortality. Both pneumonia and acute exacerbations in COPD are caused by bacteria against which there are effective vaccinations. Although the number of randomised controlled studies on bacterial vaccinations in COPD is limited, national and international guidelines endorse specific vaccinations in patients with COPD. This review will summarise the different types of vaccinations that prevent pneumonia and COPD exacerbations. We also discuss the results of early phase studies. We will mainly focus on Streptococcus pneumoniae, as this bacterium was predominantly investigated in COPD. However, we also review studies investigating vaccinations against Haemophilus influenzae, Moraxella catarrhalis, and Bordetella pertussis.

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