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1.
Life Sci ; 237: 116947, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605708

RESUMO

AIMS: Pseudomonas aeruginosa is one of the leading causes of opportunistic and hospital-acquired infections worldwide, which is frequently linked with clinical treatment difficulties. Ibuprofen, a widely used non-steroidal anti-inflammatory drug, has been previously reported to exert antimicrobial activity with the specific mechanism. We hypothesized that inhibition of P. aeruginosa with ibuprofen is involved in the quorum sensing (QS) systems. MAIN METHODS: CFU was utilized to assessed the growth condition of P. aeruginosa. Crystal violent staining and acridine orange staining was used to evaluate the biofilm formation and adherence activity. The detection of QS virulence factors such as pyocyanin, elastase, protease, and rhamnolipids were applied to investigation the anti-QS activity of ibuprofen against P. aeruginosa. The production of 3-oxo-C12-HSL and C4-HSL was confirmed by liquid chromatography/mass spectrometry analysis. qRT-PCR was used to identify the QS-related gene expression. Furthermore, we explored the binding effects between ibuprofen and QS-associated proteins with molecular docking. KEY FINDINGS: Ibuprofen inhibits P. aeruginosa biofilm formation and adherence activity. And the inhibitory effects of ibuprofen on C4-HSL levels were concentration-dependent (p < 0.05), while it has no effect on 3-oxo-C12-HSL. Moreover, ibuprofen attenuates the production of virulence factors in P. aeruginosa (p < 0.05). In addition, the genes of QS system were decreased after the ibuprofen treatment (p < 0.05). Of note, ibuprofen was binding with LuxR, LasR, LasI, and RhlR at high binding scores. SIGNIFICANCE: The antibiofilm and anti-QS activity of ibuprofen suggest that it can be a candidate drug for the treatment of clinical infections with P. aeruginosa.


Assuntos
Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Ibuprofeno/farmacologia , Pseudomonas aeruginosa/genética , Percepção de Quorum/efeitos dos fármacos , Fatores de Virulência/genética , Anti-Inflamatórios não Esteroides/farmacologia , Biofilmes/efeitos dos fármacos , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento
2.
J Microbiol ; 57(9): 781-794, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452043

RESUMO

The phytopathogenic Burkholderia species B. glumae and B. plantarii are the causal agents of bacterial wilt, grain rot, and seedling blight, which threaten the rice industry globally. Toxoflavin and tropolone are produced by these phytopathogens and are considered the most hostile biohazards with a broad spectrum of target organisms. However, despite their nonspecific toxicity, the effects of toxoflavin and tropolone on bacteria remain unknown. RNA-seq based transcriptome analysis was employed to determine the genome-wide expression patterns under phytotoxin treatment. Expression of 2327 and 830 genes was differentially changed by toxoflavin and tropolone, respectively. Enriched biological pathways reflected the down-regulation of oxidative phosphorylation and ribosome function, beginning with the inhibition of membrane biosynthesis and nitrogen metabolism under oxidative stress or iron starvation. Conversely, several systems such as bacterial chemotaxis, flagellar assembly, biofilm formation, and sulfur/taurine transporters were highly expressed as countermeasures against the phytotoxins. In addition, our findings revealed that three hub genes commonly induced by both phytotoxins function as the siderophore enterobactin, an iron-chelator. Our study provides new insights into the effects of phytotoxins on bacteria for better understanding of the interactions between phytopathogens and other microorganisms. These data will also be applied as a valuable source in subsequent applications against phytotoxins, the major virulence factor.


Assuntos
Antibacterianos/toxicidade , Burkholderia/química , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Doenças das Plantas/microbiologia , Pirimidinonas/toxicidade , Triazinas/toxicidade , Tropolona/toxicidade , Antibacterianos/metabolismo , Burkholderia/metabolismo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Oryza/microbiologia , Pirimidinonas/metabolismo , Transcriptoma/efeitos dos fármacos , Triazinas/metabolismo , Tropolona/metabolismo
3.
Nat Med ; 25(9): 1370-1376, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31406349

RESUMO

The MORDOR I trial1, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality1. However, the large but simple trial design precluded determination of the mechanisms involved. Here we examined the gut microbiome of preschool children from 30 Nigerien communities randomized to either biannual azithromycin or placebo. Gut microbiome γ-diversity was not significantly altered (P = 0.08), but the relative abundances of two Campylobacter species, along with another 33 gut bacteria, were significantly reduced in children treated with azithromycin at the 24-month follow-up. Metagenomic analysis revealed functional differences in gut bacteria between treatment groups. Resistome analysis showed an increase in macrolide resistance gene expression in gut microbiota in communities treated with azithromycin (P = 0.004). These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance.


Assuntos
Azitromicina/administração & dosagem , Infecções por Campylobacter/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Metagenômica , Campylobacter/efeitos dos fármacos , Campylobacter/patogenicidade , Infecções por Campylobacter/genética , Infecções por Campylobacter/mortalidade , Criança , Mortalidade da Criança , Pré-Escolar , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Macrolídeos/administração & dosagem , Masculino , Nigéria/epidemiologia , Análise de Sequência de RNA
4.
Microbiol Res ; 226: 19-26, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284940

RESUMO

Pseudomonas aeruginosa is one of the most common pathogens associated with nosocomial infections and a great concern to immunocompromised individuals especially in the cases of cystic fibrosis, AIDS and burn wounds. The pathogenicity of P. aeruginosa is largely directed by the quorum sensing (QS) system. Hence, QS may be considered an important therapeutic target to combat P. aeruginosa infections. The anti-quorum sensing and anti-biofilm efficacy of aromatic aldehyde, 5-hydroxymethylfurfural (5-HMF) against P. aeruginosa PAO1 were assessed. At the sub-inhibitory concentration, 5-HMF suppressed the production of QS-controlled virulence phenotypes and biofilm formation in P. aeruginosa. It was also able to significantly enhance the survival rate of C. elegans infected with P. aeruginosa. The in silico studies revealed that 5-HMF could serve as a competitive inhibitor for the auto-inducer molecules as it exhibited a strong affinity for the regulatory proteins of the QS-circuits i.e. LasR and RhlR. In addition, a significant down-regulation in the expression of QS-related genes was observed suggesting the ability of 5-HMF in mitigating the pathogenicity of P. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Furaldeído/análogos & derivados , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Percepção de Quorum/efeitos dos fármacos , Animais , Proteínas de Bactérias , Caenorhabditis elegans , Simulação por Computador , Modelos Animais de Doenças , Furaldeído/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Percepção de Quorum/genética , Taxa de Sobrevida , Transativadores , Virulência/efeitos dos fármacos , Fatores de Virulência
5.
Eur J Med Chem ; 179: 723-735, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284082

RESUMO

The biological resistance of methicillin-resistant staphylococcus aureus (MRSA) has pushed synthetic antibiotics to the forefront. To combat the resistance of MRSA, our new effort directed towards the development of novel structural candidates of enone-bridged indole nitroimidazole scaffolds, and wished to shed some light on the combination of some single pharmacophore with different biological activities. Bioassay revealed that the active compound 4b gave a satisfactory inhibition on MRSA (MIC = 1 µg/mL) and could effectively prevent the development of bacterial resistance. Mechanism exploration indicated that molecule 4b could not only intercalate into MRSA deoxyribonucleic acid (DNA), but also permeate MRSA membrane and bind with penicillin-binding protein 2a (PBP2a), then decreased the expression of three relevant genes in MRSA. Furthermore, it was able to be stored and carried by human serum albumin (HSA), and the participation of metal ions in 4b-HSA system was helpful to improve the supramolecular transport behavior. Hybrid 4b also exhibited low cytotoxicity towards normal lung epithelial cell line BEAS-2B.


Assuntos
Antibacterianos/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Indóis/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nitroimidazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Indóis/química , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Nitroimidazóis/química , Relação Estrutura-Atividade
6.
J Med Microbiol ; 68(7): 1118-1128, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31172910

RESUMO

PURPOSE: This study investigated the efficacy of the essential mineral, selenium (sodium selenite), in reducing the toxin production, spore outgrowth and antibiotic resistance of Clostridium difficile in vitro. METHODOLOGY: Two hypervirulent C. difficile isolates were cultured in brain heart infusion broth with and without a sub-minimum inhibitory concentration (sub-MIC) of sodium selenite, and the supernatant and bacterial pellet were harvested for total toxin quantitation and RT-qPCR analysis of toxin-encoding genes, respectively. Additionally, C. difficile isolates were cultured in brain heart infusion broth containing 0.5 or 1× the minimum inhibitory concentration (MIC) of either ciprofloxacin or vancomycin with or without sub-MICs of sodium selenite. Further, the effect of sodium selenite on C. difficile germination and spore outgrowth was also determined by exposing C. difficile spores to a sub-MIC of sodium selenite in a germination medium and measuring the germination and outgrowth by measuring the optical density at 600 nm. RESULTS: Sodium selenite significantly reduced C. difficile toxin synthesis, cytotoxicity and spore outgrowth. Further, the expression of the toxin production genes, tcdA and tcdB, was downregulated in the presence of sodium selenite, while sodium selenite significantly increased the sensitivity of C. difficile to ciprofloxacin , but not vancomycin, as revealed by decreased bacterial growth in samples containing ciprofloxacin+selenium compared to the antibiotic control. Although the sub-MIC of sodium selenite did not inhibit spore germination, it was capable of completely inhibiting spore outgrowth. CONCLUSION: Our results suggest that sodium selenite could potentially be used to control C. difficile and indicate that future in vivo studies are warranted.


Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/metabolismo , Clostridium difficile/efeitos dos fármacos , Selenito de Sódio/farmacologia , Esporos Bacterianos/efeitos dos fármacos , Oligoelementos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Clostridium difficile/patogenicidade , Clostridium difficile/fisiologia , Farmacorresistência Bacteriana , Enterotoxinas/genética , Enterotoxinas/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Esporos Bacterianos/fisiologia , Virulência
7.
Future Microbiol ; 14: 671-689, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31161792

RESUMO

Aim: To propose newer combinations of antibiotics effective against NDM-1-producing bacterial strains. Materials & methods: Antibiotics combinations were tested by checkerboard assay. NDM-1 protein/enzyme was expressed and purified to perform enzyme kinetics, circular dichroism and fluorescence spectroscopic studies. Results: Doripenem-cefoxitin combination and doripenem-tetracycline combination showed synergistic effect toward NDM-1-producing strains. The catalytic efficiency of NDM-1 enzyme was decreased drastically by 96.6% upon doripenem-cefoxitin treatment and by 35.54% after doripenem-tetracycline treatment. Conformational changes were observed in NDM-1 upon combination treatment. Conclusion: NDM-1-producing bacterial strains show resistance to multiple antibiotics but the combination of doripenem-cefoxitin and doripenem-tetracycline are effective against them. The combination of a carbapenem and cephamycin antibiotic is proposed for future treatment options against bacteria-producing NDM-1.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cefoxitina/farmacologia , Doripenem/farmacologia , Tetraciclina/farmacologia , beta-Lactamases/efeitos dos fármacos , Bactérias/enzimologia , Bactérias/metabolismo , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Ensaios Enzimáticos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/genética , Cinética , Testes de Sensibilidade Microbiana , Inibidores da Síntese de Proteínas/farmacologia , Termodinâmica , beta-Lactamases/análise
8.
J Microbiol Immunol Infect ; 52(4): 638-647, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31239204

RESUMO

BACKGROUND: The emergence of multiple-antibiotic-resistant (MAR) Salmonella has been a serious threat worldwide. Salmonella can invade into host cells and evade the attacks of host humoral defenses and antibiotics. Thus, a new antibacterial agent capable of inhibiting intracellular Salmonella is highly needed. METHODS: The anti-intracellular activity and cytotoxicity of drugs on intracellular bacteria and macrophages were assayed using intracellular CFU assay and MTT cell viability assay, respectively. The uptake of gentamicin into macrophage and the effect of autophagy inhibitor on loxapine's anti-intracellular Salmonella activity were assessed by using image-based high-content system. The expression of bacterial genes was measured by real-time PCR. The efflux pump activity of bacteria was measured by Hoechst accumulation assays. RESULTS: With our efforts, an antipsychotic drug, loxapine, was identified to exhibit high potency in suppressing intracellular MAR S. Typhimurium, Staphylococcus aureus, Shigella flexneri or Yersinia enterocolitica. Subsequent investigations indicated that loxapine's anti-intracellular bacteria activity was not associated with increased penetration of gentamicin into bacteria and macrophages. Loxapine didn't inhibit bacterial growth in broth at concentration up to 500 µM and has no effect on Salmonella's type III secretion system genes' expression. Blockage of autophagy also didn't reverse loxapine's anti-intracellular activity. Lastly, loxapine suppressed bacterial efflux pump activity in all bacteria tested. CONCLUSION: Altogether, our data suggested that loxapine might suppress intracellular bacteria through inhibiting of bacterial efflux pumps. In light of its unique activity, loxapine represents a promising lead compound with translational potential for the development of a new antibacterial agent against intracellular bacteria.


Assuntos
Antibacterianos/farmacologia , Antipsicóticos/farmacologia , Loxapina/farmacologia , Macrófagos/microbiologia , Salmonella typhimurium/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Proteínas de Bactérias/genética , Sobrevivência Celular/efeitos dos fármacos , Contagem de Colônia Microbiana , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Fluoroquinolonas/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Gentamicinas/farmacologia , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Proteínas de Membrana Transportadoras/genética , Camundongos , Testes de Sensibilidade Microbiana , Fenotiazinas/farmacologia , Células RAW 264.7 , Salmonella typhimurium/genética , Salmonella typhimurium/crescimento & desenvolvimento , Sorogrupo , Shigella flexneri/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Sistemas de Secreção Tipo III/efeitos dos fármacos , Sistemas de Secreção Tipo III/genética , Yersinia enterocolitica/efeitos dos fármacos
9.
J Microbiol Biotechnol ; 29(6): 973-983, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31216793

RESUMO

It is well known that iron is critical for bacterial growth and pathogenic virulence. Due to chemical similarity, Ga3+ competes with Fe3+ for binding to compounds that usually bind Fe3+, thereby interfering with various essential biological reactions. In our present study, gallium(III) nitrate [Ga(NO3)3] could repress the growth of V. splendidus Vs without complete inhibition. In the presence of Ga(NO3)3, the secretion of homogentisic acid-melanin (HGAmelanin) in V. splendidus Vs cells could be increased by 4.8-fold, compared to that in the absence of Ga(NO3)3. HGA-melanin possessed the ability to reduce Fe3+ to Fe2+. In addition, HGA-melanin increased the mRNA levels of feoA and feoB, genes coding Fe2+ transport system proteins to 1.86- and 6.1-fold, respectively, and promoted bacterial growth to 139.2%. Similarly, the mRNA expression of feoA and feoB was upregulated 4.11-fold and 2.71-fold in the presence of 640 µM Ga(NO3)3, respectively. In conclusion, our study suggested that although Ga(NO3)3 could interfere with the growth of V. splendidus Vs, it could also stimulate both the production of Fe3+-reducing HGA-melanin and the expression of feoA and feoB , which facilitate Fe2+ transport in V. splendidus Vs.


Assuntos
Gálio/farmacologia , Ferro/metabolismo , Vibrio/efeitos dos fármacos , Proteínas de Bactérias/genética , Transporte Biológico/efeitos dos fármacos , Proteínas de Transporte de Cátions/genética , Relação Dose-Resposta a Droga , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Ácido Homogentísico/química , Ácido Homogentísico/metabolismo , Ácido Homogentísico/farmacologia , Melaninas/química , Melaninas/metabolismo , Melaninas/farmacologia , Oxirredução , Sideróforos/metabolismo , Vibrio/crescimento & desenvolvimento , Vibrio/metabolismo
10.
Appl Microbiol Biotechnol ; 103(15): 6271-6285, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31161392

RESUMO

Proton magnetic resonance-based metabolomics analysis was performed to determine the global metabolite changes in pathogenic bacterium Pseudomonas aeruginosa PAO1 following exposure to quorum sensing (QS) inhibitor hordenine. Pyocyanin inhibition assay confirmed that hordenine exhibited potent QS inhibitory activity. A total of 40 metabolites were assigned by PMR spectra. Hordenine treatment resulted in the destruction of QS system in P. aeruginosa PAO1 by downregulating the expressions of genes involved in QS. The synthesis of antioxidant enzymes was repressed and the oxidative stress was enhanced due to the dysfunctional QS system of P. aeruginosa PAO1. The enhanced oxidative stress induced by the dysfunctional QS system of P. aeruginosa PAO1 altered the membrane components, enhanced membrane permeability, and disturbed energy metabolism, amino acid metabolism, and nucleotide metabolism, and would ultimately attenuate the pathogenicity of P. aeruginosa PAO1. Hordenine may have promising potential for controlling nosocomial pathogens.


Assuntos
Antibacterianos/metabolismo , Metaboloma , Pseudomonas aeruginosa/química , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Tiramina/análogos & derivados , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Metabolômica , Tiramina/metabolismo
11.
Microbiol Immunol ; 63(7): 251-260, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31166029

RESUMO

Streptococcus mutans is a cariogenic bacterium that localizes in the oral cavity. Glycyrrhetinic acid (GRA) is a major component of licorice extract. GRA and several derivatives, including disodium succinoyl glycyrrhetinate (GR-SU), are known to have anti-inflammatory effects in humans. In this study, the antimicrobial effect of GRA and its derivatives against the S. mutans UA159 strain were investigated. Minimum inhibitory concentrations (MICs) of GRA and GR-SU showed antibacterial activity against the S. mutans strain, whereas other tested derivatives did not. Because GR-SU is more soluble than GRA, GR-SU was used for further experiments. The antibacterial activity of GR-SU against 100 S. mutans strains was evaluated and it was found that all strains are susceptible to GR-SU, with MIC values below 256 µg/mL. A cell viability assay showed that GR-SU has a bacteriostatic effect on S. mutans cells. As to growth kinetics, sub-MICs of GR-SU inhibited growth. The effect of GR-SU on S. mutans virulence was then investigated. GR-SU at sub-MICs suppresses biofilm formation. Additionally, GR-SU greatly suppresses the pH drop caused by the addition of glucose and glucose-induced expression of the genes responsible for acid production (ldh and pykF) and tolerance (aguD and atpD). Additionally, expression of enolase, which is responsible for the carbohydrate phosphotransferase system, was not increased in the presence of GR-SU, indicating that GR-SU suppresses incorporation of sugars into S. mutans. In conclusion, GR-SU has antibacterial activity against S. mutans and also decreases S. mutans virulence.


Assuntos
Antibacterianos/farmacologia , Ácido Glicirretínico/farmacologia , Glycyrrhiza/química , Extratos Vegetais/farmacologia , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos/genética , Glucose/metabolismo , Ácido Glicirretínico/química , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Extratos Vegetais/química , Streptococcus mutans/genética , Streptococcus mutans/crescimento & desenvolvimento , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
12.
Nat Commun ; 10(1): 2868, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253770

RESUMO

Prokaryotes and eukaryotes alike endogenously generate the gaseous molecule hydrogen sulfide (H2S). Bacterial H2S acts as a cytoprotectant against antibiotics-induced stress and promotes redox homeostasis. In E. coli, endogenous H2S production is primarily dependent on 3-mercaptopyruvate sulfurtransferase (3MST), encoded by mstA. Here, we show that cells lacking 3MST acquire a phenotypic suppressor mutation resulting in compensatory H2S production and tolerance to antibiotics and oxidative stress. Using whole genome sequencing, we identified a non-synonymous mutation within an uncharacterized LacI-type transcription factor, ycjW. We then mapped regulatory targets of YcjW and discovered it controls the expression of carbohydrate metabolic genes and thiosulfate sulfurtransferase PspE. Induction of pspE expression in the suppressor strain provides an alternative mechanism for H2S biosynthesis. Our results reveal a complex interaction between carbohydrate metabolism and H2S production in bacteria and the role, a hitherto uncharacterized transcription factor, YcjW, plays in linking the two.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Sulfeto de Hidrogênio/metabolismo , Fatores de Transcrição/metabolismo , Substituição de Aminoácidos , Antibacterianos/farmacologia , Mapeamento Cromossômico , DNA Bacteriano , Proteínas de Ligação a DNA/genética , Dissacarídeos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/fisiologia , Ligação Proteica , RNA Mensageiro , Regulon , Fatores de Transcrição/genética
13.
Int J Mol Sci ; 20(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216645

RESUMO

Streptococcus suis is a zoonotic pathogen that causes great economic losses to the swine industry and severe threats to public health. A better understanding of its physiology would contribute to the control of its infections. Although copper is an essential micronutrient for life, it is toxic to cells when present in excessive amounts. Herein, we provide evidence that CopA is required for S. suis resistance to copper toxicity. Quantitative PCR analysis showed that copA expression was specifically induced by copper. Growth curve analyses and spot dilution assays showed that the ΔcopA mutant was defective in media supplemented with elevated concentrations of copper. Spot dilution assays also revealed that CopA protected S. suis against the copper-induced bactericidal effect. Using inductively coupled plasma-optical emission spectroscopy, we demonstrated that the role of CopA in copper resistance was mediated by copper efflux. Collectively, our data indicated that CopA protects S. suis against the copper-induced bactericidal effect via copper efflux.


Assuntos
Adaptação Biológica/genética , Proteínas de Bactérias/genética , Cobre/toxicidade , Streptococcus suis/efeitos dos fármacos , Streptococcus suis/genética , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Cobre/metabolismo , Relação Dose-Resposta a Droga , Deleção de Genes , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Streptococcus suis/metabolismo
14.
Gene ; 708: 38-48, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31128223

RESUMO

Riboswitches are gene control elements that directly bind to specific ligands to regulate gene expression without the need for proteins. They are found in all three domains of life, including Bacteria, Archaea, and Eukaryota. Riboswitches are mostly spread in bacteria and archaea. In this paper, we discuss the general distribution, structure, and function of 28 different riboswitch classes as we focus our attention on riboswitches in bacteria. Bacterial riboswitches regulate gene expression by four distinct mechanisms. They regulate the expression of a limited number of genes. However, most of these genes are responsible for the synthesis of essential metabolites without which the cell cannot function. Therefore, riboswitch distribution is also important for antibacterial drug development.


Assuntos
Bactérias/genética , Regulação Bacteriana da Expressão Gênica/genética , RNA Bacteriano/genética , Riboswitch/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Desenvolvimento de Medicamentos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , RNA Bacteriano/antagonistas & inibidores , Riboswitch/efeitos dos fármacos
15.
Nat Commun ; 10(1): 2334, 2019 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133642

RESUMO

Pseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Ácidos Graxos Insaturados/metabolismo , Histidina Quinase/metabolismo , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/fisiologia , Animais , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Modelos Animais de Doenças , Farmacorresistência Bacteriana , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/imunologia , Histidina Quinase/genética , Humanos , Lipossomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Mutagênese , Fosforilação , Polimixinas/farmacologia , Polimixinas/uso terapêutico , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
16.
World J Microbiol Biotechnol ; 35(6): 87, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31134386

RESUMO

Biofilms enable Cronobacter spp. to contaminate food, infect infants and resist different environmental stresses, especially desiccation, which is the main reason why Cronobacter can survive in powdered infant formula (PIF) for a long time. Considering the high lethality of Cronobacter infection in infants, it is important to find efficient and safe inhibitors of Cronobacter biofilms. In this study, we found that chitooligosaccharides (COS) with a molecular weight of 2000 Da efficiently inhibited Cronobacter biofilms, especially in skim milk broth. The minimum biofilm inhibitory concentration (MBIC77) of COS was as low as 20 µg/mL, which is lower than that reported in most previous studies. Besides, the elimination rate of COS for Cronobacter mature biofilms was 50% when the concentration was 10 mg/mL. COS could significantly inhibit soluble polysaccharide secretion and biofilm cell growth, as well as change the cell membrane permeability of Cronobacter. These might be the possible reasons for COS's efficient inhibition of Cronobacter biofilms. However, during the inhibition, five important genes-related to biofilm formation-flhD, flgJ, luxR, ompA, and wcaJ-were all up-regulated after COS treatment, except the gene bcsA. In summary, our findings showed that COS could be used as an efficient and safe inhibitor against Cronobacter biofilms for better control of Cronobacter contamination and infection.


Assuntos
Biofilmes/efeitos dos fármacos , Quitina/análogos & derivados , Cronobacter/efeitos dos fármacos , Animais , Biofilmes/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , Quitina/química , Quitina/farmacologia , Cronobacter/genética , Infecções por Enterobacteriaceae , Contaminação de Alimentos , Microbiologia de Alimentos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos/genética , Testes de Sensibilidade Microbiana , Leite , Peso Molecular
17.
Molecules ; 24(10)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091746

RESUMO

Strains of Acinetobacter baumannii are commensal and opportunistic pathogens that have emerged as problematic hospital pathogens due to its biofilm formation ability and multiple antibiotic resistances. The biofilm-associated pathogens usually exhibit dramatically decreased susceptibility to antibiotics. This study was aimed to investigate the correlation of biofilm-forming ability, antibiotic resistance and biofilm-related genes of 154 A. baumannii isolates which were collected from a teaching hospital in Taiwan. Biofilm-forming ability of the isolates was evaluated by crystal violet staining and observed by scanning electron microscopy. Antibiotic susceptibility was determined by disc diffusion method and minimum inhibitory concentration; the biofilm-related genes were screened by polymerase chain reaction. Results showed that among the 154 tested isolates, 15.6% of the clinical isolates were weak biofilm producers, while 32.5% and 45.4% of them possessed moderate and strong biofilm formation ability, respectively. The experimental results revealed that the multiple drug resistant isolates usually provided a higher biofilm formation. The prevalence of biofilm related genes including bap, blaPER-1, csuE and ompA among the isolated strains was 79.2%, 38.3%, 91.6%, and 68.8%, respectively. The results indicated that the antibiotic resistance, the formation of biofilm and the related genes were significantly correlated. The results of this study can effectively help to understand the antibiotic resistant mechanism and provides the valuable information to the screening, identification, diagnosis, treatment and control of clinical antibiotic-resistant pathogens.


Assuntos
Acinetobacter baumannii/fisiologia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Estudos de Associação Genética , Testes de Sensibilidade Microbiana , Taiwan
18.
Microb Pathog ; 132: 319-324, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082530

RESUMO

BACKGROUND: Host factors such as hormones are known to modulate growth, virulence and antibiotic susceptibility of bacteria. In the present study, the effect of norepinephrine (NE) and estradiol (Est) on growth and expression levels of virulence genes (usp, sfa/foc, cnf1, aer) of uropathogenic E. coli (UPEC) strains C7 and C149 were investigated. METHODS: E. coli C7 and C149 were grown in serum based SAPI broth with and without three different concentrations of norepinephrine and estradiol. Growths were determined via optical density measurement in a spectrophotometer. Real-time polymerase chain reaction was used to determine gene expression levels. Statistical analyses were performed by one way Anova Tukey's post hoc-test. RESULTS: According to our results it has been shown that, growths of bacteria could be affected in the presence of hormones which are variable according to incubation period and hormones' concentrations. Up regulation of usp, sfa/foc, cnf1 were shown to be statistically significant (p < 0.05) in the presence of low, medium levels NE and all concentrations of Est. The expression of aer was down regulated significantly in the presence of low (p < 0.001) and medium level of Est; but all levels of NE was shown to be increased the expression of aer significantly (p < 0.05). CONCLUSIONS: The results of the present study has shown once more that host factors (norepinephrine and estradiol) could influence the growth of a bacterium as well as gene expressions.


Assuntos
Estradiol/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Norepinefrina/farmacologia , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/genética , Fatores de Virulência/genética , Toxinas Bacterianas/genética , Proteínas de Transporte/genética , Proteínas de Escherichia coli/genética , Escherichia coli Uropatogênica/crescimento & desenvolvimento , Virulência/efeitos dos fármacos , Virulência/genética
19.
Molecules ; 24(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067626

RESUMO

The occurrence of damage on bacterial DNA (mediated by antibiotics, for example) is intimately associated with the activation of the SOS system. This pathway is related to the development of mutations that might result in the acquisition and spread of resistance and virulence factors. The inhibition of the SOS response has been highlighted as an emerging resource, in order to reduce the emergence of drug resistance and tolerance. Herein, we evaluated the ability of betulinic acid (BA), a plant-derived triterpenoid, to reduce the activation of the SOS response and its associated phenotypic alterations, induced by ciprofloxacin in Staphylococcus aureus. BA did not show antimicrobial activity against S. aureus (MIC > 5000 µg/mL), however, it (at 100 and 200 µg/mL) was able to reduce the expression of recA induced by ciprofloxacin. This effect was accompanied by an enhancement of the ciprofloxacin antimicrobial action and reduction of S. aureus cell volume (as seen by flow cytometry and fluorescence microscopy). BA could also increase the hyperpolarization of the S. aureus membrane, related to the ciprofloxacin action. Furthermore, BA inhibited the progress of tolerance and the mutagenesis induced by this drug. Taken together, these findings indicate that the betulinic acid is a promising lead molecule in the development helper drugs. These compounds may be able to reduce the S. aureus mutagenicity associated with antibiotic therapies.


Assuntos
Farmacorresistência Bacteriana/efeitos dos fármacos , Recombinases Rec A/genética , Staphylococcus aureus/genética , Triterpenos/farmacologia , Ciprofloxacino/efeitos adversos , Ciprofloxacino/farmacologia , DNA Bacteriano/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Mutagênese/efeitos dos fármacos , Mutagênese/genética , Resposta SOS (Genética)/efeitos dos fármacos , Resposta SOS (Genética)/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Fatores de Virulência/genética
20.
Meat Sci ; 155: 16-19, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31055229

RESUMO

The combined effect of temperature, water activity (aw) and NaCl content, usually found in dry-cured ham, on the growth and expression of the virulence and stress-related genes of Listeria monocytogenes was evaluated in a dry-cured ham model system. The highest growth of this pathogen was observed at 15 °C and, at 0.98 and 0.96 aw values. At 0.94 and 0.92 aw values, moderate NaCl levels stimulated the L. monocytogenes growth and repressed the expression of the four tested genes. At 7 °C, the expression of the plcA gene was favored while at 15 °C the hly and iap genes were activated. Preventive actions based on temperature, aw and salt content should be taken to minimise risks associated with growth and gene expression of L. monocytogenes in dry-cured ham.


Assuntos
Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/metabolismo , Produtos da Carne/microbiologia , Cloreto de Sódio/farmacologia , Animais , Microbiologia de Alimentos , Conservação de Alimentos/métodos , Listeria monocytogenes/genética , Suínos , Temperatura Ambiente , Virulência/genética , Água
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