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1.
Artigo em Inglês | MEDLINE | ID: mdl-35525881

RESUMO

Endolysins are bacteriophage-derived lytic enzymes with antimicrobial activity. The action of endolysins against Gram-negative bacteria remains a challenge due to the physical protection of the outer membrane. However, recent research has demonstrated that signal-anchor-release (SAR) endolysins permeate the outer membrane of Gram-negative bacteria. This study investigates 2628 putative endolysin genes identified in 183,298 bacteriophage genomes. Previously, bioinformatic approaches resulted in a database of 66 SAR endolysins. This manuscript almost doubles the list with 53 additional SAR endolysin candidates. Forty-eight of the putative SAR endolysins described in this study contained one muramidase catalytic domain, and five included additional cell wall-binding domains at the C-terminus. For the moment, SAR domains are found in four protein families: glycoside hydrolase family 19 (GH19), glycoside hydrolase family 24 (GH24), glycoside hydrolase family 25 (GH25), and glycoside hydrolase family 108 (GH108). These SAR lysis are clustered in eight groups based on biochemical properties and domain presence/absence. Therefore, in this study, we expand the arsenal of endolysin candidates that might act against Gram-negative bacteria and develop a consult database for antimicrobial proteins derived from bacteriophages.

2.
Chem Res Toxicol ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35537067

RESUMO

The emergence and re-emergence of bacterial strains resistant to multiple drugs represent a global health threat, and the search for novel biological targets is a worldwide concern. AhpC are enzymes involved in bacterial redox homeostasis by metabolizing diverse kinds of hydroperoxides. In pathogenic bacteria, AhpC are related to several functions, as some isoforms are characterized as virulence factors. However, no inhibitor has been systematically evaluated to date. Here we show that the natural ent-kaurane Adenanthin (Adn) efficiently inhibits AhpC and molecular interactions were explored by computer assisted simulations. Additionally, Adn interferes with growth and potentializes the effect of antibiotics (kanamycin and PMBN), positioning Adn as a promising compound to treat infections caused by multiresistant bacterial strains.

3.
Braz J Microbiol ; 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35446010

RESUMO

Salmonella enterica causes Salmonellosis, an important infection in humans and other animals. The number of multidrug-resistant (MDR) phenotypes associated with Salmonella spp. isolates is increasing worldwide, causing public health concern. Here, we aim to characterize the antimicrobial-resistant phenotype of 789 non-typhoidal S. enterica strains isolated from human infections in the state of São Paulo, Brazil, along 20 years (2000-2019). Among the non-susceptible isolates, 31.55, 14.06, and 13.18% were resistant to aminoglycosides, tetracycline, and ß-lactams, respectively. Moreover, 68 and 11 isolates were considered MDR and Extended Spectrum ß-Lactamase (ESBL) producers, respectively, whereas one isolate was colistin-resistant. We selected four strains to obtain a draft of the Genome Sequence; one S. Infantis (ST32), one S. Enteritidis (ST11), one S. I 4,[5],12:i:- (ST19), and one S. Typhimurium (ST313). Among them, three presented at least one of the following antimicrobial resistance genes (AMR) linked to mobile DNA: blaTEM-1B, dfrA1, tetA, sul1, floR, aac(6')-laa, and qnrE1. This is the first description of the plasmid-mediated quinolone resistance (PMQR) gene qnrE1 in a clinical isolate of S. I 4,[5],12:i:-. The S. Typhimurium is a colistin-resistant isolate, but did not harbor mcr genes, but it presented mutations within the mgrB, pmrB, and pmrC regions that might be linked to the colistin-resistant phenotype. The virulence pattern of the four isolates resembled the virulence pattern of the highly pathogenic S. Typhimurium UK-1 reference strain in assays involving the in vivo Galleria mellonella model. In conclusion, most isolates studied here are susceptible, but a small percentage present an MDR or ESBL-producer and pathogenic phenotype. Sequence analyses revealed plasmid-encoded AMR genes, such as ß-lactam and fluoroquinolone resistance genes, indicating that these characteristics can be potentially disseminated among other bacterial strains.

4.
Future Microbiol ; 17: 199-218, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35040703

RESUMO

Leishmaniasis is a zoonotic and neglected disease, which represents an important public health problem worldwide. Different species of Leishmania are associated with different manifestations, and a practical problem that can worsen the condition of hosts infected with Leishmania is the secondary infection caused by bacteria. This review aims to examine the importance and prevalence of bacteria co-infection during leishmaniasis and the nature of this ecological relationship. In the cases discussed in this review, the facilitation phenomenon, defined as any interaction where the action of one organism has a beneficial effect on an organism of another species, was considered in the Leishmania-bacteria interaction, as well as the effects on one another and their consequences for the host.


Assuntos
Leishmania , Leishmaniose , Bactérias/genética , Humanos , Leishmaniose/epidemiologia
5.
Bioact Mater ; 10: 281-294, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34901546

RESUMO

Cancer is a deadly disease that is globally and consistently one of the leading causes of mortality every year. Despite the availability of chemotherapy, radiotherapy, immunotherapy, and surgery, a cure for cancer has not been attained. Recently, exosomes have gained significant attention due to the therapeutic potential of their various components including proteins, lipids, nucleic acids, miRNAs, and lncRNAs. Exosomes constitute a set of tiny extracellular vesicles with an approximate diameter of 30-100 nm. They are released from different cells and are present in biofluids including blood, cerebrospinal fluid (CSF), and urine. They perform crucial multifaceted functions in the malignant progression of cancer via autocrine, paracrine, and endocrine communications. The ability of exosomes to carry different cargoes including drug and molecular information to recipient cells make them a novel tool for cancer therapeutics. In this review, we discuss the major components of exosomes and their role in cancer progression. We also review important literature about the potential role of exosomes as vaccines and delivery carriers in the context of cancer therapeutics.

6.
Antibiotics (Basel) ; 10(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34680724

RESUMO

The prevalence of multidrug-resistant Gram-negative bacteria is a public health concern. Bacteriophages and bacteriophage-derived lytic enzymes have been studied in response to the emergence of multidrug-resistant bacteria. The availability of tRNAs and endolysin toxicity during recombinant protein expression is circumvented by codon optimization and lower expression levels using inducible pET-type plasmids and controlled cultivation conditions, respectively. The use of polyhistidine tags facilitates endolysin purification and alters antimicrobial activity. Outer membrane permeabilizers, such as organic acids, act synergistically with endolysins, but some endolysins permeate the outer membrane of Gram-negative bacteria per se. However, the outer membrane permeation mechanisms of endolysins remain unclear. Other strategies, such as the co-administration of endolysins with polymyxins, silver nanoparticles, and liposomes confer additional outer membrane permeation. Engineered endolysins comprising domains for outer membrane permeation is also a strategy used to overcome the current challenges on the control of multidrug-resistant Gram-negative bacteria. Metagenomics is a new strategy for screening endolysins with interesting antimicrobial properties from uncultured phage genomes. Here, we review the current state of the art on the heterologous expression of endolysin, showing the potential of bacteriophage endolysins in controlling bacterial infections.

7.
World J Microbiol Biotechnol ; 37(9): 151, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398340

RESUMO

The aim of the current review is to address updated research on a natural pigment called violacein, with emphasis on its production, biological activity and applications. New information about violacein's action mechanisms as antitumor agent and about its synergistic action in drug delivery systems has brought new alternatives for anticancer therapy. Thus, violacein is introduced as reliable drug capable of overcoming at least three cancer hallmarks, namely: proliferative signaling, cell death resistance and metastasis. In addition, antimicrobial effects on several microorganisms affecting humans and other animals turn violacein into an attractive drug to combat resistant pathogens. Emphasis is given to effects of violacein combined with different agents, such as antibiotics, anticancer agents and nanoparticles. Although violacein is well-known for many decades, it remains an attractive compound. Thus, research groups have been making continuous effort to help improving its production in recent years, which can surely enable its pharmaceutical and chemical application as multi-task compound, even in the cosmetics and food industries.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Indóis/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cosméticos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Indústria Alimentícia , Humanos
8.
J Dairy Sci ; 104(6): 7210-7224, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33773789

RESUMO

In this observational study, phenotypic and genotypic patterns of antimicrobial resistance (AMR) in Klebsiella pneumoniae isolated from intramammary infections, clinical mastitis, fresh feces, rectal swabs, animal hindlimbs, and bulk tank milk samples from Brazilian dairy herds were investigated. In addition, we identified specific genetic variants present among extended-spectrum ß-lactamase (ESBL) producers. We obtained 169 isolates of K. pneumoniae from 2009 to 2011 on 24 Brazilian dairy farms located in 4 Brazilian states. The AMR profile of all isolates was determined using disk-diffusion assays. The antimicrobial panel included drugs commonly used as mastitis treatment in Brazilian dairy herds (gentamicin, cephalosporins, sulfamethoxazole-trimethoprim, tetracycline) as well as antimicrobials of critical importance for human health (meropenem, ceftazidime, fluoroquinolones). The K. pneumoniae isolates resistant to tetracycline, fluoroquinolones, sulfamethoxazole-trimethoprim, or chloramphenicol were screened for presence of drug-specific AMR genes [tet, qnr, aac(6')-Ib, floR, catA2, cm1A, dfr, sul] using PCR. In addition, we identified ESBL genes present among ESBL-producers by using whole genome sequencing. Genomes were assembled and annotated, and patterns of AMR genes were investigated. Resistance was commonly detected against tetracycline (22.5% of all isolates), streptomycin (20.7%), and sulfamethoxazole-trimethoprim (9.5%). Antimicrobial resistance rates were higher in K. pneumoniae isolated from intramammary infections in comparison with isolates from feces (19.2 and 0% of multidrug resistance in intramammary and fecal isolates, respectively). In contrast, no difference in AMR rates was observed when contrasting hind limbs and isolates from intramammary infections. The genes tetA, sul2, and floR were the most frequently observed AMR genes in K. pneumoniae resistant to tetracycline, sulfamethoxazole-trimethoprim, and chloramphenicol, respectively. The tetA gene was present exclusively in isolates from milk. The genes blaCTX-M8 and blaSHV-108 were present in 3 ESBL-producing K. pneumoniae, including an isolate from bulk tank milk. The 3 isolates were of sequence type 281 and had similar mobile genetic elements and virulence genes. Our study reinforced the epidemiological importance and dissemination of blaCTX-M-8 pST114 plasmid in food-producing animals in Brazil.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Brasil , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/veterinária , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana/veterinária , beta-Lactamases/genética
9.
Microbiol Res ; 242: 126622, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33099234

RESUMO

The increasing interest in products with functional properties has encouraged the search for new lactic acid bacteria (LAB) present in natural sources, as traditional fermented foods. In this study, a large set of wild LAB isolates (n = 220) from Brazilian artisanal cheeses (BAC) were assessed for their probiotic and biopreservation potential. First, the rational selection was performed. From the tested isolates, 92 (41.8 %) were resistant to low pH (2 and 3). These isolates were submitted to bile salt (0.4 % Oxgall powder) resistance, and 22 were selected and submitted to adhesion assays. The autoaggregation values ranged from 68.5-99% and were considered moderate to high (20-70 %). Hydrophobicity values varied significantly between LAB (5.0-64.3%), and seven isolates presented values higher than 40 %. All selected LAB (n=22) were capable of adhering to Caco-2 (> 70 %) cells, and none isolate displayed any tested gene for biogenic amine production. Most isolates (18/22) showed less than 1 log CFU reduction after passage through the simulated gastrointestinal tract (GIT) conditions. A total of twenty isolates satisfied key in vitro criteria to be considered as probiotics. A hierarchical cluster analysis (HCA) was performed, and two clusters were observed, showing high variability between Lactobacillus plantarum isolates regarding adhesion properties and survival to GIT stress and one influence of the source of isolation on these properties. After screening, the antimicrobial activity of Lb. plantarum (1QB77) was tested in microcheeses in which survival of two relevant pathogenic bacteria (Staphylococcus aureus and Listeria monocytogenes) was monitored along ripening and after a simulated GIT passage, concomitantly. L. plantarum (1QB77) has shown the ability to reach high counts (∼ 9 log CFU/g) at the end of ripening. This isolate was also able to reduce counts of S. aureus and L. monocytogenes in microcheeses in approx. 2.3 and 2.5 log CFU/g, respectively, until the 21st day of ripening; and about 3.2 and 3.5 log CFU/g after simulated GIT passage. Overall, the assessment of the probiotic properties of a large set of LAB was fundamental for gaining insights on the technological, functional, and potential regional traits of wild LAB isolates that can be used to develop starter cultures for tailored applications.


Assuntos
Queijo/microbiologia , Microbiologia de Alimentos , Lactobacillales/isolamento & purificação , Lactobacillales/fisiologia , Probióticos/isolamento & purificação , Anti-Infecciosos/farmacologia , Aderência Bacteriana , Ácidos e Sais Biliares , Brasil , Células CACO-2 , Conservação de Alimentos , Trato Gastrointestinal/microbiologia , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Lactobacillus plantarum , Listeria monocytogenes , Programas de Rastreamento , Probióticos/farmacologia , Staphylococcus aureus
10.
Recent Pat Biotechnol ; 15(2): 102-111, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33349223

RESUMO

BACKGROUND: This review outlines the current impact of violacein-derivative materials in several technological areas through patents. METHODS: A comprehensive examination of patent databases on violacein demonstrated the relevance of this pigment, as well as the pertinent topics related to its technological development in order to obtain adaptable new pharmaceuticals, cosmetics, and new quality fiber materials, together with other applications of violacein in different areas. RESULTS: At present, there is no efficient and economical technique for violacein preparation at the industrial scale. Many attempts have been made, but none have overcome the challenge of being an effective and inexpensive process. However, some potential applications of violacein in fields such as biomedicine make the pigment worthy of continuous investigation. In particular, violacein patents covering biosynthesis for different applications have been reported recently. CONCLUSION: Violacein has been used as a unique pigment in distinct specialty areas, such as in medical and industrial fields. This review of patents provides an update on violacein innovations that are useful for researchers working in the expanding and interesting field of biotechnology with natural pigments.


Assuntos
Indóis , Patentes como Assunto , Biotecnologia
11.
Res Microbiol ; 172(2): 103794, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33347948

RESUMO

Treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria is challenging, a potential solution for which is the use of bacteriophage-derived lytic enzymes. However, the exogenous action of bacteriophage lysins against Gram-negative bacteria is hindered due to the presence of an impermeable outer membrane in these bacteria. Nevertheless, recent research has demonstrated that some lysins are capable of permeating the outer membrane of Gram-negative bacteria with the help of signal peptides. In the present study, we investigated the genomes of 309 bacteriophages that infect Gram-negative pathogens of clinical interest in order to determine the evolutionary markers of signal peptide-containing lysins. Complete genomes displayed 265 putative lysins, of which 17 (6.41%) contained signal-arrest-release motifs and 41 (15.47%) contained cleavable signal peptides. There was no apparent relationship between host specificity and lysin diversity. Nevertheless, the evolution of lysin genes might not be independent of the rest of the bacteriophage genome once pan-genome clustering and lysin diversity appear to be correlated. In addition, signal peptide- and signal-arrest-release-containing lysins were monophyletically distributed in the protein cladogram, suggesting that the natural selection of holin-independent lysins is divergent. Our study screened 58 (21.89%) out of 265 potential candidates for in vitro experimentation against MDR bacteria.


Assuntos
Bacteriófagos/enzimologia , Bacteriófagos/genética , Bactérias Gram-Negativas/virologia , Sinais Direcionadores de Proteínas , Proteínas Virais/genética , Motivos de Aminoácidos , Membrana Externa Bacteriana , Bacteriólise , Biodiversidade , Farmacorresistência Bacteriana Múltipla , Evolução Molecular , Genoma Bacteriano , Genoma Viral , Bactérias Gram-Negativas/genética , Proteínas Virais/isolamento & purificação
12.
Food Res Int ; 137: 109643, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33233222

RESUMO

Cronobacter spp. are opportunistic pathogens that cause serious infections, especially in infants, elderly, and immunocompromised people. Dehydrated infant foods are the main vehicle associated with infections caused by these bacteria. Thus, this study aims to investigate the occurrence of Cronobacter spp. in 152 commercial samples of dehydrated infant formulas (77 samples) and dehydrated infant cereals (75 samples), as well as characterize the isolates. Polymerase Chain Reaction (PCR) and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF/MS) methods for isolate identification were used, and their results compared. Furthermore, the susceptibility to 11 antibiotics was tested, and DNA sequencing of one isolate with multi-drug resistance was analyzed. No contamination in the infant formula samples was found, whereas 17.33% (13/75) of the infant cereal samples presented contamination with Cronobacter sakazakii. The identification results by PCR and MALDI-TOF/MS were divergent for some isolates. The antimicrobial resistance results showed a high incidence of resistance to cefazolin (94.4%) besides resistance to amoxicillin (9.45%), cefpodoxime (5.55%), streptomycin (1.35%), and trimethoprim/sulfamethoxazole (1.35%). Whole genome sequencing of one multi-drug resistant isolate showed six genes associated with antimicrobial resistance and an 82% possibility of being a human pathogen based on the presence of virulence factors. The presence of Cronobacter spp. in infant foods represents a risk for the infant's health. Moreover, the presence of a pathogenic multi-drug resistant isolate in infant's food reinforces the necessity of improving food safety policies to protect young children.


Assuntos
Cronobacter sakazakii , Cronobacter , Idoso , Criança , Pré-Escolar , Cronobacter/genética , Cronobacter sakazakii/genética , Microbiologia de Alimentos , Humanos , Lactente , Fórmulas Infantis , Análise de Sequência de DNA
13.
Mol Immunol ; 127: 95-106, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32949849

RESUMO

Leishmania infantum infection may cause visceral leishmaniasis (VL), a fatal disease having worldwide distribution, that may be silent or asymptomatic. The latter indicates that immunity is naturally developed in some individuals, and, therefore, a vaccine against VL would be possible. Molecular mechanisms of gene expression are being understood in Leishmania, and this knowledge may be useful for vaccine development. The aim of this study was developing an attenuated strain by regulating the expression of toxic proteins in a stage specific manner. For that purpose, the 3' UTR of an amastin gene, known by its increased expression in the amastigote phase, was selected for direct the expression of exogenous proteins. This construct (pFL-AMA), firstly, was proved effective for the expression of mCherry specifically in the intracellular form of L. infantum, as demonstrated by fluorescence microscopy, flow cytometry and Western blotting. Afterwards, mCherry coding sequence was replaced, in the pFL-AMA plasmid, by either egg avidin or the active form of bovine trypsin. Viability of transfected parasites was evaluated in promastigote axenic cultures and in in vitro infection of macrophages. Both lines of transfected parasites showed a limited capacity to multiply inside macrophages. BALB/c mice were inoculated intraperitoneally (i.p.) with a single dose consisting of 2 × 106L. infantum promastigotes transfected with plasmids bearing the toxic genes. After 10 weeks post-inoculation, no parasites were recovered by limiting dilution in either liver or spleen, but a specific immunological response was detected. The immunization with transfected parasites induced cellular and humoral immune responses with activation of TCD4+, TCD8+ and B cells, having a TH1-type response with increased levels of pro-inflammatory cytokines such as IFN-γ, TNF-α and IL-6. In parallel groups of mice, a challenge consisting on 1 × 106 virulent parasites of either L. infantum (inoculated i.p.) or L. amazonensis subcutaneously (s.c.) was performed. Vaccinated mice, challenged with L. infantum, showed lower parasite burdens in liver, spleen and bone marrow than infected mice with WT L. infantum (non-vaccinated); similarly, vaccinated mice developed smaller footpad inflammation than control group. These data support this strategy as an efficient immunization system aimed to the development of vaccines against different forms of leishmaniasis.


Assuntos
Leishmania infantum/fisiologia , Leishmania/fisiologia , Leishmaniose/prevenção & controle , Leishmaniose/parasitologia , Plasmídeos/metabolismo , Toxinas Biológicas/metabolismo , Transfecção , Animais , Feminino , Regulação da Expressão Gênica , Humanos , Imunidade Celular , Imunidade Humoral , Imunização , Leishmania/patogenicidade , Leishmania infantum/crescimento & desenvolvimento , Leishmania infantum/patogenicidade , Leishmaniose/imunologia , Estágios do Ciclo de Vida , Camundongos Endogâmicos BALB C , Parasitos/metabolismo , Parasitos/patogenicidade , Proteínas de Protozoários/metabolismo , Virulência
14.
Bioorg Chem ; 100: 103921, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32464403

RESUMO

Enterococci are gram-positive, widespread nosocomial pathogens that in recent years have developed resistance to various commonly employed antibiotics. Since finding new infection-control agents based on secondary metabolites from organisms has proved successful for decades, natural products are potentially useful sources of compounds with activity against enterococci. Herein are reported the results of a natural product library screening based on a whole-cell assay against a gram-positive model organism, which led to the isolation of a series of anacardic acids identified by analysis of their spectroscopic data and by chemical derivatizations. Merulinic acid C was identified as the most active anacardic acid derivative obtained against antibiotic-resistant enterococci. Fluorescence microscopy analyses showed that merulinic acid C targets the bacterial membrane without affecting the peptidoglycan and causes rapid cellular ATP leakage from cells. Merulinic acid C was shown to be synergistic with gentamicin against Enterococcus faecium, indicating that this compound could inspire the development of new antibiotic combinations effective against drug-resistant pathogens.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Gentamicinas/farmacologia , Sinergismo Farmacológico , Enterococcus faecium/crescimento & desenvolvimento , Enterococcus faecium/metabolismo , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Hidroxibenzoatos/farmacologia
15.
J Nat Prod ; 83(1): 55-65, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31895573

RESUMO

A new method of screening was developed to generate 770 organic and water-soluble fractions from extracts of nine species of marine sponges, from the growth media of 18 species of marine-derived fungi, and from the growth media of 13 species of endophytic fungi. The screening results indicated that water-soluble fractions displayed significant bioactivity in cytotoxic, antibiotic, anti-Leishmania, anti-Trypanosoma cruzi, and inhibition of proteasome assays. Purification of water-soluble fractions from the growth medium of Penicillium solitum IS1-A provided the new glutamic acid derivatives solitumine A (1), solitumine B (2), and solitumidines A-D (3-6). The structures of compounds 1-6 have been established by analysis of spectroscopic data, chemical derivatizations, and vibrational circular dichroism calculations. Although no biological activity could be observed for compounds 1-6, the new structures reported for 1-6 indicate that the investigation of water-soluble natural products represents a relevant strategy in finding new secondary metabolites.


Assuntos
Glutamatos/química , Regiões Antárticas , Fungos/química , Estrutura Molecular , Penicillium/química , Água
16.
Biotechnol Lett ; 41(12): 1433-1437, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31650420

RESUMO

OBJECTIVES: To examine the synergistic antibacterial activity of violacein and silver nanoparticles (AgNPs) against ATCC bacteria, Staphylococcus aureus, Escherichia coli and two bacteria isolated from bovine mastitis. METHODS: Violacein from Chromobacterium violaceum and biogenic AgNPs from Fusarium oxysporum were evaluated in antimicrobial tests. RESULTS: E. coli isolates were not inhibited by violacein at concentrations up to 400 µM and they showed sensitivity for AgNPs between 62.5 and 250 µM. Staphylococcus aureus showed sensitivity to violacein with MIC of 200 µM, and the MIC with AgNPs between 250 µM and 125 µM. It was also tested the association between the two compounds through a concentration gradient and was observed the reduction of the MIC in the combination for both strains. CONCLUSION: The bactericidal effect of violacein against S. aureus was better when combined with AgNPs (synergistic).


Assuntos
Antibacterianos/farmacologia , Indóis/farmacologia , Nanopartículas Metálicas , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Bovinos , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Mastite Bovina/microbiologia , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
17.
Sci Rep ; 9(1): 5486, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940839

RESUMO

Burkholderia seminalis strain TC3.4.2R3 is an endophytic bacterium isolated from sugarcane roots that produces antimicrobial compounds, facilitating its ability to act as a biocontrol agent against phytopathogenic bacteria. In this study, we investigated the thermoregulation of B. seminalis TC3.4.2R3 at 28 °C (environmental stimulus) and 37 °C (host-associated stimulus) at the transcriptional and phenotypic levels. The production of biofilms and exopolysaccharides such as capsular polysaccharides and the biocontrol of phytopathogenic fungi were enhanced at 28 °C. At 37 °C, several metabolic pathways were activated, particularly those implicated in energy production, stress responses and the biosynthesis of transporters. Motility, growth and virulence in the Galleria mellonella larvae infection model were more significant at 37 °C. Our data suggest that the regulation of capsule expression could be important in virulence against G. mellonella larvae at 37 °C. In contrast, B. seminalis TC3.4.2R3 failed to cause death in infected BALB/c mice, even at an infective dose of 107 CFU.mL-1. We conclude that temperature drives the regulation of gene expression in B. seminalis during its interactions with the environment.


Assuntos
Burkholderia/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , Mariposas/efeitos dos fármacos , Polissacarídeos Bacterianos/genética , Adaptação Fisiológica , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Regulação da Temperatura Corporal , Burkholderia/genética , Burkholderia/metabolismo , Regulação Bacteriana da Expressão Gênica , Larva/efeitos dos fármacos , Larva/microbiologia , Camundongos , Mariposas/crescimento & desenvolvimento , Mariposas/microbiologia , Fenótipo , Polissacarídeos Bacterianos/metabolismo , Polissacarídeos Bacterianos/farmacologia , Temperatura
18.
ACS Infect Dis ; 5(4): 539-549, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30693760

RESUMO

Violacein is a tryptophan-derived purple pigment produced by environmental bacteria, which displays multiple biological activities, including strong inhibition of Gram-positive pathogens. Here, we applied a combination of experimental approaches to identify the mechanism by which violacein kills Gram-positive bacteria. Fluorescence microscopy showed that violacein quickly and dramatically permeabilizes B. subtilis and S. aureus cells. Cell permeabilization was accompanied by the appearance of visible discontinuities or rips in the cytoplasmic membrane, but it did not affect the cell wall. Using in vitro experiments, we showed that violacein binds directly to liposomes made with commercial and bacterial phospholipids and perturbs their structure and permeability. Furthermore, molecular dynamics simulations were employed to reveal how violacein inserts itself into lipid bilayers. Thus, our combined results demonstrate that the cytoplasmic membrane is the primary target of violacein in bacteria. The implications of this finding for the development of violacein as a therapeutic agent are discussed.


Assuntos
Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Indóis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/química , Bacillus subtilis/química , Bacillus subtilis/crescimento & desenvolvimento , Membrana Celular/química , Indóis/química , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Staphylococcus aureus/química , Staphylococcus aureus/crescimento & desenvolvimento
19.
ACS Appl Mater Interfaces ; 11(6): 6589-6604, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30653288

RESUMO

Because of their antibacterial activity, silver nanoparticles (AgNPs) have been explored in biomedical applications. Similarly, nitric oxide (NO) is an important endogenous free radical with an antimicrobial effect and toxicity toward cancer cells that plays pivotal roles in several processes. In this work, biogenic AgNPs were prepared using green tea extract and the principles of green chemistry, and the NO donor S-nitrosoglutathione (GSNO) was prepared by the nitrosation of glutathione. To enhance the potentialities of GSNO and AgNPs in biomedical applications, the NO donor and metallic nanoparticles were individually or simultaneously incorporated into polymeric solid films of poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG). The resulting solid nanocomposites were characterized by several techniques, and the diffusion profiles of GSNO and AgNPs were investigated. The results demonstrated the formation of homogeneous PVA/PEG solid films containing GSNO and nanoscale AgNPs that are distributed in the polymeric matrix. PVA/PEG films containing AgNPs demonstrated a potent antibacterial effect against Gram-positive and Gram-negative bacterial strains. GSNO-containing PVA/PEG films demonstrated toxicity toward human cervical carcinoma and human prostate cancer cell lines. Interestingly, the incorporation of AgNPs in PVA/PEG/GSNO films had a superior effect on the decrease of cell viability of both cancer cell lines, compared with cells treated with films containing GSNO or AgNPs individually. To our best knowledge, this is the first report to describe the preparation of PVA/PEG solid films containing GSNO and/or biogenically synthesized AgNPs. These polymeric films might find important biomedical applications as a solid material with antimicrobial and antitumorigenic properties.


Assuntos
Anti-Infecciosos/química , Nanopartículas Metálicas/química , Polietilenoglicóis/química , Álcool de Polivinil/química , S-Nitrosoglutationa/química , Prata/química , Anti-Infecciosos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Química Verde , Humanos , Chá/química , Chá/metabolismo
20.
Front Microbiol ; 9: 1780, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30186241

RESUMO

Salmonella enterica infection is a major public health concern worldwide, particularly when associated with other medical conditions. The serovars Typhimurium and Enteritidis are frequently associated with an invasive illness that primarily affects immunocompromised adults and children with HIV, malaria, or malnutrition. These serovars can also cause infections in a variety of animal hosts, and they are the most common isolates in poultry materials. Here, we described S. Enteritidis mutants, where hupA and hupB genes were deleted, and evaluated their potential use as live-attenuated vaccine candidates. In vitro, the mutants behaved like S. Typhimurium described previously, but there were some particularities in macrophage invasion and survival experiments. The virulence and immunogenicity of the mutant lacking both hupA and hupB (PT4ΔhupAB) were evaluated in a BALB/c mice model. This mutant was highly attenuated and could, therefore, be administrated at doses higher than 109 CFU/treatment, which was sufficient to protect all treated mice challenged with the wild-type parental strain with a single dose. Additionally, the PT4ΔhupAB strain induced production of specific IgG and IgA antibodies against Salmonella and TH1-related cytokines (IFN-γ and TNF-α), indicating that this strain can induce systemic and mucosal protection in the murine model. Additional studies are needed to better understand the mechanisms that lead to attenuation of the double-mutant PT4ΔhupAB and to elucidate the immune response induced by immunization using this strain. However, our data allow us to state that hupAB mutants could be potential candidates to be explore as live-attenuated vaccines.

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