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1.
Food Chem ; 336: 127744, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32781352

RESUMO

Cardoon (Cynara cardunculus L.) bracts were collected at different maturation stages to investigate seasonal changes in the phenolic compounds profile and in vitro bioactivities. Among the 12 phenolic compounds tentatively identified, 3,5-O-dicaffeoylquinic acid (21.83 mg/g extract) and apigenin-7-O-glucuronide (10.6 mg/g extract) were the most abundant. Immature bracts (C1: principal growth stage (PGS) 5) had the highest phenolic compounds content, and anti-inflammatory (IC50 = 72 µg/mL) and cytotoxic (GI50 of 30-79 µg/mL) activities. Moreover, extract C1 inhibited efficiently the formation of thiobarbituric acid reactive substances (TBARS; IC50 = 26.8 µg/mL), while extract C8 (PGS 8/9) was more effective against oxidative haemolysis (IC50 38 and 75 µg/mL). The highest antibacterial and antifungal activities were attributed to samples C1 and C6 (PGS 7/8) and samples C2 (PGS 5/6) and C4 (PGS 6/7), respectively. Overall, the obtained results suggest the seasonal changes of polyphenolic composition and bioactivity of cardoon bracts of variable maturity.


Assuntos
Cynara/química , Fenóis/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cynara/crescimento & desenvolvimento , Cynara/metabolismo , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Fenóis/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Células RAW 264.7 , Estações do Ano
2.
An Acad Bras Cienc ; 92(suppl 2): e20201216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33084762

RESUMO

Staphylococcus aureus (S. aureus) is a highly versatile Gram-positive bacterium that is carried asymptomatically by up to 30% of healthy people, while being a major cause of healthcare-associated infections, making it a worldwide problem in clinical medicine. The adaptive evolution of S. aureus strains is demonstrated by its remarkable capacity to promptly develop high resistance to multiple antibiotics, thus limiting treatment choice. Nowadays, there is a continuous demand for an alternative to the use of antibiotics for S. aureus infections and a strategy to control the spread or to kill phylogenetically related strains. In this scenario, bacteriocins fit as with a promising and interesting alternative. These molecules are produced by a range of bacteria, defined as ribosomally synthesized peptides with bacteriostatic or bactericidal activity against a wide range of pathogens. This work reviews ascertained the main antibiotic-resistance mechanisms of S. aureus strains and the current, informative content concerning the applicability of the use of bacteriocins overlapping the use of conventional antibiotics in the context of S. aureus infections. Besides, we highlight the possible application of these biomolecules on an industrial scale in future work.


Assuntos
Bacteriocinas , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Positivas , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus
3.
Nat Commun ; 11(1): 5232, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067466

RESUMO

Glycopeptide antibiotics (GPAs) are essential for the treatment of severe infectious diseases caused by Gram-positive bacteria. The emergence and spread of GPA resistance have propelled the search for more effective GPAs. Given their structural complexity, genetic intractability, and low titer, expansion of GPA chemical diversity using synthetic or medicinal chemistry remains challenging. Here we describe a synthetic biology platform, GPAHex (GPA Heterologous expression), which exploits the genes required for the specialized GPA building blocks, regulation, antibiotic transport, and resistance for the heterologous production of GPAs. Application of the GPAHex platform results in: (1) a 19-fold increase of corbomycin titer compared to the parental strain, (2) the discovery of a teicoplanin-class GPA from an Amycolatopsis isolate, and (3) the overproduction and characterization of a cryptic nonapeptide GPA. GPAHex provides a platform for GPA production and mining of uncharacterized GPAs and provides a blueprint for chassis design for other natural product classes.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Glicopeptídeos/síntese química , Glicopeptídeos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Biologia Sintética/métodos , Antibacterianos/química , Descoberta de Drogas , Genoma Bacteriano , Glicopeptídeos/química , Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana
4.
Nat Commun ; 11(1): 4935, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004797

RESUMO

Gramicidin A (1) is a peptide antibiotic that disrupts the transmembrane ion concentration gradient by forming an ion channel in a lipid bilayer. Although long used clinically, it is limited to topical application because of its strong hemolytic activity and mammalian cytotoxicity, likely arising from the common ion transport mechanism. Here we report an integrated high-throughput strategy for discovering analogues of 1 with altered biological activity profiles. The 4096 analogue structures are designed to maintain the charge-neutral, hydrophobic, and channel forming properties of 1. Synthesis of the analogues, tandem mass spectrometry sequencing, and 3 microscale screenings enable us to identify 10 representative analogues. Re-synthesis and detailed functional evaluations find that all 10 analogues share a similar ion channel function, but have different cytotoxic, hemolytic, and antibacterial activities. Our large-scale structure-activity relationship studies reveal the feasibility of developing analogues of 1 that selectively induce toxicity toward target organisms.


Assuntos
Antibacterianos/farmacologia , Descoberta de Drogas/métodos , Gramicidina/análogos & derivados , Ensaios de Triagem em Larga Escala/métodos , Animais , Antibacterianos/química , Linhagem Celular Tumoral , Química Farmacêutica , Eritrócitos , Estudos de Viabilidade , Bactérias Gram-Positivas/efeitos dos fármacos , Gramicidina/química , Gramicidina/farmacologia , Hemólise/efeitos dos fármacos , Concentração Inibidora 50 , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Coelhos , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem
5.
Anim Sci J ; 91(1): e13464, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33021004

RESUMO

Methyl-mannosylerythritol lipid (MEL), a new sugar esterified lipid synthesized by Pseudozyma aphidis, was assessed for its functionality in modulating rumen fermentation and microbiota toward more propionate and less methane production. A pure culture study using rumen representatives showed that MEL selectively inhibited the growth of most Gram-positive bacteria including Streptococcus bovis, ruminococci, and Fibrobacter succinogenes, but not Gram-negative bacteria such as Megasphaera elsdenii, Succinivibrio dextrinosolvens, and Selenomonas ruminantium. A batch culture study revealed that MEL significantly decreased methane production in a dose-dependent manner with accumulation of hydrogen, while propionate production was enhanced. A continuous culture (Rusitec) study confirmed all of these changes. A feeding study revealed that sheep fed a MEL diet showed an increased proportion of propionate, while proportions of acetate and butyrate were decreased without affecting total VFA level. These changes disappeared after cessation of MEL feeding. Based on these results, dietary application of MEL can favorably modify rumen fermentation in terms of the efficiency of dietary energy utilization.


Assuntos
Ração Animal , Antibacterianos , Dieta/veterinária , Suplementos Nutricionais , Fermentação/efeitos dos fármacos , Glicolipídeos/administração & dosagem , Glicolipídeos/farmacologia , Bactérias Gram-Positivas/crescimento & desenvolvimento , Rúmen/metabolismo , Rúmen/microbiologia , Tensoativos/farmacologia , Animais , Relação Dose-Resposta a Droga , Metabolismo Energético , Masculino , Metano/metabolismo , Propionatos/metabolismo , Ovinos
6.
Int J Nanomedicine ; 15: 6935-6944, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061360

RESUMO

Introduction: Nanoparticle solutions have been studied to improve antimicrobial effect. The aim of this study was to develop, characterize, and evaluate the in vitro and in vivo antiseptic efficacy of 0.25% aqueous-based chlorhexidine nanoemulsion (NM-Cl 0.25% w/v). Methods: The NM-Cl 0.25% w/v (2.5mg/mL) and free chlorhexidine nanoemulsion (FCN; same composition of NM-Cl without the molecule of chlorhexidine) were synthetized by the spontaneous emulsification method. Characterization analyses of physical and chemical properties were performed. The NM-Cl 0.25% w/v was compared with chlorhexidine 0.5% alcohol base (CS-Cl 0.5%) in vitro studies (microdilution study and kill curve study), and in vivo study (antisepsis of rats dorsum). Kruskal-Wallis test was used between groups and inside the same group, at different sample times and the Mann-Whitney test was performed when difference was detected. Results: The NM-Cl 0.25% w/v presented adequate physicochemical characteristics for a nanoemulsion, revealing a more basic pH than FCN and difference between zeta potential of NM-Cl 0.25% w/v and FCN. The NM-Cl 0.25% w/v and CS-Cl 0.5% solutions were more effective on Gram-positive than on Gram-negative bacteria (p≤0.05). NM-Cl 0.25% w/v presented upper antiseptic effect in the microdilution study and residual antiseptic effect was maintained for a longer time when compared to CS-Cl 0.5% (kill curve study). The four-fold (minimal inhibitory concentration) of NM-Cl 0.25% were the formulations with most durable effect within those tested, presenting residual effect until T6 for both bacteria. In the in vivo study, both formulations (NM-Cl 0.25% w/v and CS-Cl 0.5%) had a reduction of the microorganisms in the skin of the rats (p<0.0001) not revealing any difference between the formulations at different times, showing the antiseptic effect of NM-Cl (p≤0.05). Conclusion: Both in vitro and in vivo experiments demonstrated that NM-Cl showed promising future as an antiseptic for cutaneous microbiota.


Assuntos
Anti-Infecciosos Locais/farmacologia , Clorexidina/farmacologia , Emulsões/química , Nanoestruturas/química , Animais , Anti-Infecciosos Locais/química , Clorexidina/química , Emulsões/farmacologia , Etanol/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Nanoestruturas/uso terapêutico , Ratos Wistar , Pele/efeitos dos fármacos , Pele/microbiologia
7.
BMC Bioinformatics ; 21(Suppl 14): 367, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998698

RESUMO

BACKGROUND: Essential genes are those genes that are critical for the survival of an organism. The prediction of essential genes in bacteria can provide targets for the design of novel antibiotic compounds or antimicrobial strategies. RESULTS: We propose a deep neural network for predicting essential genes in microbes. Our architecture called DEEPLYESSENTIAL makes minimal assumptions about the input data (i.e., it only uses gene primary sequence and the corresponding protein sequence) to carry out the prediction thus maximizing its practical application compared to existing predictors that require structural or topological features which might not be readily available. We also expose and study a hidden performance bias that effected previous classifiers. Extensive results show that DEEPLYESSENTIAL outperform existing classifiers that either employ down-sampling to balance the training set or use clustering to exclude multiple copies of orthologous genes. CONCLUSION: Deep neural network architectures can efficiently predict whether a microbial gene is essential (or not) using only its sequence information.


Assuntos
Bactérias/genética , Genes Essenciais , Redes Neurais de Computação , Área Sob a Curva , Análise por Conglomerados , Códon , Bactérias Gram-Negativas/genética , Bactérias Gram-Positivas/genética , Curva ROC
8.
Int J Food Microbiol ; 335: 108890, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-32971300

RESUMO

The bioactivity of essential oils applied in foods to act as natural preservatives can be reduced due to interactions with other components of the food matrix. Microencapsulation can help to increase the functionality of these compounds. In addition, the electrostatic interaction between proteins and polysaccharides can result in double-layered encapsulating structures, ensuring greater protection to essential oils than using only protein as surface active agent. In this work, pink pepper essential oil was microencapsulated by spray drying of single-layer emulsions, stabilized by soy protein isolate (SPI), and of double-layer emulsions, stabilized by soy protein isolate/high methoxyl pectin (SPI/HMP). Pink pepper essential oil showed predominance of α-pinene, ß-pinene, ß-mircene, δ-3-carene, d-limonene, and germacrene D. Compared to SPI microcapsules, SPI/HMP microcapsules better preserved the total volatile content identified in pure oil, showed less water adsorption during storage at relative humidity ≥75% and improved antimicrobial properties. When stored for 20 days (25 °C/RH = 52.8%), both microcapsules allowed more gradual release of volatiles compared with non-encapsulated oil. Microencapsulation by spray drying did not have negative effects on the antioxidant activity of the encapsulated oil, as the microcapsules showed similar results to the non-encapsulated oil, around 11 µg Trolox/mg of oil. After storage, however, the non-encapsulated oil showed greater losses of its antioxidant activity due to higher rates of volatile release. In the in vitro antimicrobial activity assay, both microcapsules inhibited growth of Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes and Listeria innocua, although no inhibition was observed against Gram-negative bacteria. When added in milk, both microcapsules reduced bacterial growth, whereas non-encapsulated oil showed no satisfactory inhibition. Faster reduction of microbial growth in milk was observed for SPI/HMP microcapsules. Inhibition results were better for skim milk than for whole milk, suggesting that the interaction of essential oil with other lipids present in milk decreased its bioactivity. Microencapsulation positively affected the functionality of pink pepper essential oil, highlighting its potential for application as a natural preservative in food products.


Assuntos
Anacardiaceae/química , Antibacterianos/química , Conservantes de Alimentos/química , Óleos Voláteis/química , Antibacterianos/farmacologia , Cápsulas/química , Cápsulas/farmacologia , Dessecação , Emulsões/química , Emulsões/farmacologia , Conservantes de Alimentos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Óleos Voláteis/farmacologia , Pectinas/química , Proteínas de Soja/química , Terebintina/química , Terebintina/farmacologia
9.
Braz J Infect Dis ; 24(5): 380-385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866434

RESUMO

BACKGROUND: Gram-negative bacilli (GNB), notably Acinetobacter spp., Pseudomonas spp., and Klebsiella spp., are becoming increasingly resistant to carbapenems and are associated with high health care costs and mortality, becoming a global concern. OBJECTIVE: To determine the prevalence rates of carbapenem resistance among Acinetobacter spp., Pseudomonas spp., and Klebsiella spp. in the main sites of nosocomial infection at a tertiary care hospital in southern Brazil and the consequent therapeutic implications. METHODS: Cultures processed at the institution's laboratory in 2017 were analyzed, and those positive for Acinetobacter spp., Pseudomonas spp., and Klebsiella spp. were identified. Antibiograms were evaluated for meropenem sensitivity following the Clinical Laboratory Standards Institute guidelines. RESULTS: Acinetobacter spp. had the lowest prevalence among the three GNB, and resistance of this pathogen to meropenem at different sites of infection ranged from 36% (blood) to 82% (respiratory tract). Pseudomonas spp. was highly prevalent at the respiratory tract (31%) and had a high resistance rate to meropenem in rectal swab samples (71%), but a relatively low frequency at infection sites (skin/soft tissue, 13%; blood, 25%). Klebsiella spp. was identified in 7.5% of the blood cultures and 15% of the urine cultures and was the chief colonizer among all pathogens, representing 54% of all rectal swab samples, of which 53% were meropenem resistant. At sites of infection, rates of Klebsiella spp. resistant to meropenem ranged from 19% (skin) to 55% (vascular catheter). CONCLUSIONS: The prevalence of carbapenem-resistant GNB at our hospital was relatively low compared to national and international data; thus, meropenem remains a good therapeutic option against these bacteria. Other antibiotics effective against GNB, such as ceftazidime, cefepime, and piperacillin-tazobactam, can be used in most cases, while meropenem should be reserved for patients with sepsis. Strict contact precaution measures are still needed, given the high resistance rate observed at the colonizing site.


Assuntos
Carbapenêmicos , Bactérias Gram-Positivas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Brasil , Farmacorresistência Bacteriana , Bactérias Gram-Negativas , Humanos , Testes de Sensibilidade Microbiana , Prevalência
10.
J Chromatogr A ; 1629: 461511, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-32896687

RESUMO

The scientific interest on the plant Cannabis sativa L., and in particular on its non-psychoactive or fibre-type variety (hemp), has been highly increasing in recent years, due to the pharmaceutical and nutraceutical potential of its bioactive compounds. This plant is indeed characterized by a very rich chemical composition, which encompasses different classes of constituents, such as cannabinoids and terpenes. In this context, the bioanalytical testing of hemp extracts can be difficult and time-consuming. Effect-directed analysis (EDA) by the combination of high-performance thin-layer chromatography (HPTLC) with biological and enzymatic assays represents one of the latest tools available for the rapid bioprofiling of complex matrices, such as plant extracts. In this ambit, the aim of this project was the non-targeted screening of inflorescence extracts from ten different hemp varieties for components exhibiting radical scavenging, antibacterial, enzyme inhibiting and estrogen-like effects. By HPTLC-EDA, the hemp samples exhibited strong antibacterial activities against both Gram-positive Bacillus subtilis and especially Gram-negative Aliivibrio fischeri bacteria, and also estrogen-like activity. They also inhibited α- and ß-glucosidase, tyrosinase and acetylcholinesterase. The characterization of two prominently multipotent bioactive compound zones was finally achieved by HPTLC-HRMS and preliminary assigned as cannabidiolic acid and cannabidivarinic acid.


Assuntos
Cannabis/química , Cromatografia em Camada Delgada/métodos , Extratos Vegetais/análise , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Antibacterianos/análise , Antibacterianos/química , Antibacterianos/farmacologia , Canabinoides/análise , Cannabis/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Extratos Vegetais/química
12.
BMC Infect Dis ; 20(1): 673, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938424

RESUMO

BACKGROUND: Urinary tract infection is one of the most common bacterial infections in children. Understanding the characteristics of uropathogens and their antimicrobial susceptibility pattern in a particular setting can provide evidence for the appropriate management of cases. This study aimed to assess the bacterial profile of urinary tract infection, their antimicrobial susceptibility pattern and associated factors among clinically suspected children attending at Felege-Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia. METHODS: A hospital-based cross-sectional study was conducted from February-April, 2019. A systematic sampling technique was employed. A mid-stream urine sample was inoculated on cystine lactose electrolyte deficient media and incubated for 24-48 h. Sub-culturing was done on Mac-Conkey and blood agar. Antimicrobial susceptibility test was done on Muller-Hinton agar. A binary logistic regression model was used to see the association between dependent and independent factors. A p-value< 0.05 at 95% CI was considered as statistically significant. RESULTS: The overall prevalence of urinary tract infection was 16.7% (95% CI 12.4-21.1). Both Gram-negative and Gram-positive bacterial isolates were recovered with a rate of 44/50 (88%) and 6/50 (12%) respectively. Among Gram-negative isolates, E. coli 28/44(63.6%) was predominant while S. saprophyticus 2/6(33.3%) was prevalent among Gram-positive bacterial isolates. Overall, a high level of resistance to ampicillin, augmentin, and tetracycline was shown by Gram-negative bacteria with a rate of 44/44(100%), 39/44(88.6%), and36/44 (81.8%) respectively. About 33/50(66%) of overall multidrug resistance was observed (95% CI 52-78). About six Gram-negative bacterial isolates were extended spectrum beta-lactamase (ESBL) producers. Having a history of urinary tract infection (P-0.003, AOR 1.86-22.15) and male uncircumcision (p-0.00, AOR 5.5-65.35) were the independent variables that associate for urinary tract infections. CONCLUSION: In the present study, the prevalence of urinary tract infection among children was high and considerably a high proportion of multidrug resistance was observed. This result will have a significant impact on the selection of appropriate antimicrobial agents for the treatment of urinary tract infection.


Assuntos
Infecções Urinárias/diagnóstico , Adolescente , Antibacterianos/farmacologia , Criança , Pré-Escolar , Estudos Transversais , Farmacorresistência Bacteriana Múltipla , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Etiópia/epidemiologia , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Hospitais , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Razão de Chances , Estudos Prospectivos , Infecções Urinárias/microbiologia , beta-Lactamases/genética , beta-Lactamases/metabolismo
13.
Sci Rep ; 10(1): 13875, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807805

RESUMO

Respiratory protection is key in infection prevention of airborne diseases, as highlighted by the COVID-19 pandemic for instance. Conventional technologies have several drawbacks (i.e., cross-infection risk, filtration efficiency improvements limited by difficulty in breathing, and no safe reusability), which have yet to be addressed in a single device. Here, we report the development of a filter overcoming the major technical challenges of respiratory protective devices. Large-pore membranes, offering high breathability but low bacteria capture, were functionalized to have a uniform salt layer on the fibers. The salt-functionalized membranes achieved high filtration efficiency as opposed to the bare membrane, with differences of up to 48%, while maintaining high breathability (> 60% increase compared to commercial surgical masks even for the thickest salt filters tested). The salt-functionalized filters quickly killed Gram-positive and Gram-negative bacteria aerosols in vitro, with CFU reductions observed as early as within 5 min, and in vivo by causing structural damage due to salt recrystallization. The salt coatings retained the pathogen inactivation capability at harsh environmental conditions (37 °C and a relative humidity of 70%, 80% and 90%). Combination of these properties in one filter will lead to the production of an effective device, comprehensibly mitigating infection transmission globally.


Assuntos
Filtros de Ar/microbiologia , Antibacterianos/química , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Máscaras/microbiologia , Membranas Artificiais , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Dispositivos de Proteção Respiratória/microbiologia , Cloreto de Sódio/química , Aerossóis , Antibacterianos/farmacologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Cristalização , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Temperatura Alta , Humanos , Umidade , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Cloreto de Sódio/farmacologia
14.
Nat Commun ; 11(1): 4157, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814767

RESUMO

Swarming is a form of collective bacterial motion enabled by flagella on the surface of semi-solid media. Swarming populations exhibit non-genetic or adaptive resistance to antibiotics, despite sustaining considerable cell death. Here, we show that antibiotic-induced death of a sub-population benefits the swarm by enhancing adaptive resistance in the surviving cells. Killed cells release a resistance-enhancing factor that we identify as AcrA, a periplasmic component of RND efflux pumps. The released AcrA interacts on the surface of live cells with an outer membrane component of the efflux pump, TolC, stimulating drug efflux and inducing expression of other efflux pumps. This phenomenon, which we call 'necrosignaling', exists in other Gram-negative and Gram-positive bacteria and displays species-specificity. Given that adaptive resistance is a known incubator for evolving genetic resistance, our findings might be clinically relevant to the rise of multidrug resistance.


Assuntos
Antibacterianos/metabolismo , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Resistência Microbiana a Medicamentos/fisiologia , Transdução de Sinais/fisiologia , Adaptação Fisiológica/fisiologia , Antibacterianos/farmacologia , Bactérias/classificação , Proteínas da Membrana Bacteriana Externa/metabolismo , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/classificação , Bactérias Gram-Positivas/metabolismo , Viabilidade Microbiana/efeitos dos fármacos , Periplasma/metabolismo , Especificidade da Espécie
15.
Emerg Microbes Infect ; 9(1): 1958-1964, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32815458

RESUMO

Objectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P<0.0001). The most common infections were respiratory, blood-stream and urinary infections, and in respiratory infections, the most detected pathogens were gram-negative bacteria (26, 50.00%), following by gram-positive bacteria (14, 26.92%), virus (6, 11.54%), fungi (4, 7.69%), and others (2, 3.85%). Respiratory Infection rate post high flow, tracheal intubation, and tracheotomy were 12.90% (4/31), 30.43% (7/23), and 92.31% (12/13) respectively. Secondary infections would lead to lower discharge rate and higher mortality rate. Conclusion Our study originally illustrated secondary infection proportion in severe and critical COVID-19 patients. Culture accompanied with metagenomics sequencing increased pathogen diagnostic rate. Secondary infections risks increased after receiving invasive respiratory ventilations and intravascular devices, and would lead to a lower discharge rate and a higher mortality rate.


Assuntos
Bacteriemia/patologia , Infecções Bacterianas/patologia , Infecções por Coronavirus/patologia , Fungemia/patologia , Micoses/patologia , Infecções Oportunistas/patologia , Pneumonia Viral/patologia , Infecções Respiratórias/patologia , Infecções Urinárias/patologia , Idoso , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/virologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/virologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Estado Terminal , Feminino , Fungemia/microbiologia , Fungemia/mortalidade , Fungemia/virologia , Fungos/patogenicidade , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/patogenicidade , Humanos , Unidades de Terapia Intensiva , Pulmão/microbiologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Micoses/mortalidade , Micoses/virologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/mortalidade , Infecções Oportunistas/virologia , Pandemias , Pneumonia Viral/microbiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Respiração Artificial/efeitos adversos , Infecções Respiratórias/microbiologia , Infecções Respiratórias/mortalidade , Infecções Respiratórias/virologia , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Infecções Urinárias/microbiologia , Infecções Urinárias/mortalidade , Infecções Urinárias/virologia
16.
PLoS One ; 15(8): e0238056, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857801

RESUMO

BACKGROUND: There are variations in recommendations from different guidelines regarding the indications for repeat lumbar puncture (LP) in young infants with the diagnosis of bacterial meningitis. OBJECTIVE: To evaluate the frequency of repeat LPs and the characteristics of cerebrospinal fluid (CSF) parameters in repeated sampling and their predictive values for adverse outcomes in a national cohort. METHODS: This cohort study included infants born January 1, 2013 through December 31, 2014, who had proven or suspected bacterial meningitis within the first 90 days of life at seven paediatric tertiary care hospitals across Canada, and who underwent a repeat LP at the discretion of the treating physicians. RESULTS: Forty-nine of 111 infants (44%) underwent repeat LP at a median of 5 (IQR: 3, 13) days after the LP that led to the diagnosis of bacterial meningitis. Those who had meningitis caused by gram negative bacilli were more likely to have repeat LP than those with gram positive bacteria (77% versus 57%; p = 0.012). White blood cell (WBC) count on the second spinal tap yielded an area under the curve of 0.88 for predicting sequelae of meningitis at discharge from the hospital, with a cut-off value of 366 × 106/L, providing a sensitivity of 91% and specificity of 88%. CONCLUSION: In this multi-centre retrospective cohort study, infants with gram negative meningitis were more likely to have repeated LP. A high WBC on the second CSF sample was predictive of adverse outcome at the time of discharge from the hospital.


Assuntos
Líquido Cefalorraquidiano/citologia , Meningites Bacterianas/diagnóstico , Área Sob a Curva , Canadá , Estudos de Coortes , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Contagem de Leucócitos , Masculino , Meningites Bacterianas/microbiologia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Punção Espinal , Centros de Atenção Terciária
17.
BMC Infect Dis ; 20(1): 578, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758181

RESUMO

BACKGROUND: Gram-positive anaerobic (GPA) bacteria inhabit different parts of the human body as commensals but can also cause bacteremia. In this retrospective observational study, we analyzed GPA bacteremia pathogens before (2013-2015) and after (2016-2018) the introduction of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). METHOD: We conducted a retrospective observational study by searching the microbiology database to identify all positive GPA blood cultures of patients with GPA bacteremia diagnosed using the new technique, MALDI-TOF MS, between January 1, 2016 and December 31, 2018; and using a conventional phenotypic method between January 1, 2013 and December 31, 2015 at a single tertiary center in Japan. Parvimonas micra (P. micra) (17.5%) was the second most frequently identified GPA (MALDI-TOF MS); we then retrospectively reviewed electronic medical records for 25 P. micra bacteremia cases at our hospital. We also conducted a literature review of published cases in PubMed from January 1, 1980, until December 31, 2019; 27 cases were retrieved. RESULTS: Most cases of P. micra bacteremia were identified after 2015, both, at our institute and from the literature review. They were of mostly elderly patients and had comorbid conditions (malignancies and diabetes). In our cases, laryngeal pharynx (7/25, 28%) and gastrointestinal tract (GIT; 6/25, 24%) were identified as the most likely sources of bacteremia; however, the infection source was not identified in 9 cases (36%). P. micra bacteremia were frequently associated with spondylodiscitis (29.6%), oropharyngeal infection (25.9%), intra-abdominal abscess (14.8%), infective endocarditis (11.1%), septic pulmonary emboli (11.1%), and GIT infection (11.1%) in the literature review. Almost all cases were treated successfully with antibiotics and by abscess drainage. The 30-day mortalities were 4 and 3.7% for our cases and the literature cases, respectively. CONCLUSIONS: Infection sites of P. micra are predominantly associated with GIT, oropharyngeal, vertebral spine, intra-abdominal region, pulmonary, and heart valves. Patients with P. micra bacteremia could have good prognosis following appropriate treatment.


Assuntos
Bacteriemia/diagnóstico , Firmicutes/química , Bactérias Gram-Positivas/química , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Hemocultura , Discite/microbiologia , Feminino , Firmicutes/isolamento & purificação , Trato Gastrointestinal/microbiologia , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Japão , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Orofaringe/microbiologia , Estudos Retrospectivos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Resultado do Tratamento , Adulto Jovem
18.
Food Chem ; 333: 127458, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32673952

RESUMO

Artemisia species are aromatic herbs used as food and/or ethnomedicine worldwide; however, the use of these plants is often impeded by misidentification. Here, molecular and chemotaxonomic approaches were combined to assist in the morphology-based authentication of Artemisia species, and Artemisia indica and Artemisia argyi were identified. The plant extracts and compounds obtained from these species, 1,8-cineole, carveol, α-elemene, α-farnesene, methyl linolenate, diisooctyl phthalate inhibited the growth of food-borne harmful bacteria. Mechanistic studies showed that the extract and active compounds of A. indica killed Gram-negative and -positive bacteria via destruction of the bacterial membrane. Finally, in vivo data demonstrated that A. indica protected against bacterial infection in mice as evidenced by survival rate, bacterial load in organs, gut pathology, diarrhea, body weight, food consumption, stool weight, and pathology score. A. indica and its active compounds have potential for use as food supplements for food-borne bacterial diseases and thus improve human health.


Assuntos
Antibacterianos/farmacologia , Artemisia/química , Compostos Fitoquímicos/análise , Extratos Vegetais/farmacologia , Animais , Antibacterianos/química , Carga Bacteriana , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Plantas Medicinais/química , Intoxicação Alimentar por Salmonella/tratamento farmacológico , Intoxicação Alimentar por Salmonella/mortalidade , Taiwan
19.
Rev Col Bras Cir ; 47: e20202471, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32667581

RESUMO

PURPOSE: the purpose of this research was to identify the sociodemographic and microbiological characteristics and antibiotic resistance rates of patients with diabetic foot infections, hospitalized in an emergency reference center. METHODS: it was an observational and transversal study. The sociodemographic data were collected by direct interview with the patients. During the surgical procedures, specimens of tissue of the infected foot lesions were biopsied to be cultured, and for bacterial resistance analysis. RESULTS: the sample consisted of 105 patients. The majority of patierns were men, over 50 years of age, married and with low educational level. There was bacterial growth in 95 of the 105 tissue cultures. In each positive culture only one germ was isolated. There was a high prevalence of germs of the Enterobacteriaceae family (51,5%). Gram-negative germs were isolated in 60% of cultures and the most individually isolated germs were the Gram-positive cocci, Staphylococcus aureus (20%) and Enterococcus faecalis (17,9%). Regarding antibiotic resistance rates, a high frequency of Staphylococcus aureus resistant to methicillin (63,0%) and to ciprofloxacin (55,5%) was found; additionally, 43,5% of the Gram-negative isolated germs were resistant to ciprofloxacin. CONCLUSIONS: the majority of patients were men, over 50 years of age, married and with low educational level. The most prevalent isolated germs from the infected foot lesions were Gram-negative bacteria, resistant to ciprofloxacin, and the individually most isolated germ was the methicillin resistant Staphylococcus aureus.


Assuntos
Antibacterianos/uso terapêutico , Pé Diabético/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Dermatopatias Bacterianas/microbiologia , Idoso , Antibacterianos/farmacologia , Complicações do Diabetes , Diabetes Mellitus , Pé Diabético/tratamento farmacológico , Resistência Microbiana a Medicamentos , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Infecções , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Dermatopatias Bacterianas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia
20.
Food Chem ; 332: 127391, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603920

RESUMO

The objectives of the present work were to investigate the influence of Gum Arabic (GA) on the physicochemical properties and ultra-high temperature (UHT) processability of ß-lactoglobulin(ß-lg)-stabilized d-limonene emulsions. Moreover, we also wanted to evaluate the antimicrobial efficiency and mechanism of ß-lg-GA bilayer d-limonene emulsions. Physicochemically stable bilayer emulsions could be formed with an optimal concentration of GA (1.00 wt%), which showed a higher tolerance to both flocculation and coalescence, as well as better protective effects on d-limonene against UHT-treatment that up to 94.32% of d-limonene was retained in emulsions. Likewise, it is also noteworthy that no obvious difference in the minimal inhibitory concentration could be found between bilayer emulsions with or without UHT processing. Moreover, the antimicrobial effects of the bilayer emulsions with UHT treatment were shown to be dose-dependent, which was evidenced from the results of scanning electron microscopy and the determination of released cell constituents. Keywords: ß-lactoglobulin; gum arabic; d-limonene emulsion; physicochemical stability; UHT processability, antimicrobial efficiency.


Assuntos
Antibacterianos/química , Emulsões/química , Manipulação de Alimentos/métodos , Limoneno/química , Bicamadas Lipídicas/química , Antibacterianos/farmacologia , Elasticidade , Emulsões/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Goma Arábica/química , Temperatura Alta , Lactoglobulinas/química , Testes de Sensibilidade Microbiana , Viscosidade
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