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1.
Pharmaceutics ; 12(8)2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32751176

RESUMO

The persistence of multidrug resistance among microorganisms has directed a mandate towards a hunt for the development of alternative therapeutic modalities. In this context, antimicrobial photodynamic therapy (aPDT) is sprouted as a novel strategy to mitigate biofilms and planktonic cells of pathogens. Nanoparticles (NPs) are reported with unique intrinsic and antimicrobial properties. Therefore, silver NPs (AgNPs) were investigated in this study to determine their ability to potentiate the aPDT of photosensitizer against Staphylococcus aureus and Pseudomonas aeruginosa. Biologically synthesized AgNPs were surface coated with methylene blue (MB) and studied for their aPDT against planktonic cells and biofilms of bacteria. The nano-conjugates (MB-AgNPs) were characterized for their size, shape and coated materials. MB-AgNPs showed significant phototoxicity against both forms of test bacteria and no toxicity was observed in the dark. Moreover, activity of MB-AgNPs was comparatively higher than that of the free MB, which concludes that MB-AgNPs could be an excellent alternative to combat antibiotic resistant bacteria.

2.
J Microbiol Biotechnol ; 30(4): 571-582, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31986566

RESUMO

Quorum sensing (QS)-mediated infections cause severe diseases in human beings. The control of infectious diseases by inhibiting QS using antipathogenic drugs is a promising approach as antibiotics are proving inefficient in treating these diseases. Marine fungal (Pestalotiopsis sydowiana PPR) extract was found to possess effective antipathogenic characteristics. The minimum inhibitory concentration (MIC) of the fungal extract against test pathogen Pseudomonas aeruginosa PAO1 was 1,000 µg/ml. Sub-MIC concentrations (250 and 500 µg/ml) of fungal extract reduced QS-regulated virulence phenotypes such as the production of pyocyanin, chitinase, protease, elastase, and staphylolytic activity in P. aeruginosa PAO1 by 84.15%, 73.15%, 67.37%, 62.37%, and 33.65%, respectively. Moreover, it also reduced the production of exopolysaccharides (74.99%), rhamnolipids (68.01%), and alginate (54.98%), and inhibited the biofilm formation of the bacteria by 90.54%. In silico analysis revealed that the metabolite of P. sydowiana PPR binds to the bacterial QS receptor proteins (LasR and RhlR) similar to their respective natural signaling molecules. Cyclo(-Leu-Pro) (CLP) and 4-Hydroxyphenylacetamide (4-HPA) were identified as potent bioactive compounds among the metabolites of P. sydowiana PPR using in silico approaches. The MIC values of CLP and 4-HPA against P. aeruginosa PAO1 were determined as 250 and 125 µg/ml, respectively. All the antivirulence assays were conducted at sub-MIC concentrations of CLP (125 µg/ml) and 4-HPA (62.5 µg/ml), which resulted in marked reduction in all the investigated virulence factors. This was further supported by gene expression studies. The findings suggest that the metabolites of P. sydowiana PPR can be employed as promising QS inhibitors that target pathogenic bacteria.

3.
Microb Pathog ; 138: 103811, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31644930

RESUMO

The bacterial cell communication also termed as Quorum sensing (QS) system was involved in the expression of several virulence traits during Pseudomonas infection. The attenuating of this bacterial cell communication system is an attractive approach for the management of bacterial infections without the complication of resistance development. In this respect, the marine environment has gained significant attention due to its biodiversity and as a source of novel bioactive compounds. The present study aimed to screening effective QS inhibitors from marine associated fungal species for QS inhibitors. Twelve morphologically distinct fungal isolates were isolated from the wood of Avicennia marina from marine ecosystem. The anti-QS potential of fungal crude extract from was investigated in biosensor strain and test bacterium, Chromobacterium violaceum and Pseudomonas aeruginosa PAO1, respectively. Promising anti-QS activity was observed in the crude extract of one of the fungal isolate and identified by molecular characterization using internal transcribed spacer (ITS) region as Blastobotrys parvus PPR3. The anti-virulence and antibiofilm effects of ethyl acetate fractions from PPR3 against P. aeruginosa PAO1 were evaluated. The fungal metabolites responsible for the anti-QS activity of fungal crude extract was identified using gas chromatography-mass spectrometry (GC-MS). Furthermore, molecular docking studies were performed to understand the interaction of bioactive compounds with as receptors of P. aeruginosa PAO1. The crude extract of PPR3 showed reduction in different virulence traits of P. aeruginosa PAO1 such as production of pyocyanin, elastase, protease, chitinase, swimming and swarming motility, biofilm formation, exopolysaccharide production and alginate production at different sub-MIC concentrations. Interaction of bioactive metabolites with LasR and RhlR receptors of P. aeruginosa PAO1 was reported. The findings of the present study suggested that metabolites of B. parvus PPR3 interfere with QS system of P. aeruginosa PAO1 and alters the production of virulence factors.


Assuntos
Antibiose , Organismos Aquáticos , Biofilmes , Pseudomonas aeruginosa/fisiologia , Percepção de Quorum , Saccharomycetales/fisiologia , Antibacterianos/biossíntese , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Modelos Moleculares , Filogenia , Percepção de Quorum/efeitos dos fármacos , Saccharomycetales/classificação , Saccharomycetales/isolamento & purificação , Relação Estrutura-Atividade , Virulência/efeitos dos fármacos
4.
Microb Pathog ; 131: 128-134, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30959097

RESUMO

Quorum sensing (QS) is the cell density dependent communication network which coordinates the production of pathogenic determinants in majority of pathogenic bacteria. Pseudomonas aeruginosa causes hospital-acquired infections by virtue of its well-defined QS network. As the QS regulatory network in P. aeruginosa regulates the virulence determinants and antibiotic resistance, attenuating the QS system seems to be influential in developing next-generation anti-infective agents. In the current study, the QS attenuation potential of a flavonoid, mosloflavone was investigated against P. aeruginosa virulence and biofilm formation. Mosloflavone inhibited the pyocyanin production, LasB elastase and chitinase by 59.52 ±â€¯2.74, 35.90 ±â€¯4.34 and 61.18 ±â€¯5.52% respectively. The QS regulated biofilm formation and development was also reduced when supplemented with sub-MIC of mosloflavone. The gene expression studies of mosloflavone using RT-PCR depicted its ability to down-regulate the expression levels of QS regulated virulence genes such as lasI (60.64%), lasR (91.70%), rhlI (57.30%), chiC (90.20%), rhlA (47.87%), rhlR (21.55%), lasB (37.80%), phzM (42.40%), toxA (61.00%), aprA (58.4%), exoS (78.01%), algD (46.60%) and pelA (50.45%). The down-regulation of QS virulence phenotypes by mosloflavone could be attributed to its binding affinity with the QS regulatory proteins, LasR and RhlR by competitively inhibiting the binding of natural autoinducers as evidenced from simulation studies. Mosloflavone also exhibited promising potential in controlling bacterial infection in Caenorhabditis elegans model system, in vivo. The anti-biofilm and anti-QS potential of mosloflavone in the current study illustrated the candidature of mosloflavone as a promising biocide.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Flavonoides/farmacologia , Fenótipo , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Alginatos , Animais , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Caenorhabditis elegans , Quitinases/metabolismo , Modelos Animais de Doenças , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Glicolipídeos/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Metaloendopeptidases/genética , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , Piocianina/metabolismo , Transativadores/genética , Virulência/efeitos dos fármacos , Virulência/genética , Fatores de Virulência/genética
5.
Biofouling ; 35(1): 89-103, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30835535

RESUMO

In the present study, the antimicrobial and antibiofilm efficacy of toluidine blue (TB) encapsulated in mesoporous silica nanoparticles (MSN) was investigated against Pseudomonas aeruginosa and Staphylococcus aureus treated with antimicrobial photodynamic therapy (aPDT) using a red diode laser 670 nm wavelength, 97.65 J cm-2 radiant exposure, 5 min). Physico-chemical techniques (UV-visible (UV-vis) absorption, photoluminescence emission, excitation, and FTIR) and high-resolution transmission electron microscopy (HR-TEM) were employed to characterize the conjugate of TB encapsulated in MSN (TB MSN). TB MSN showed maximum antimicrobial activities corresponding to 5.03 and 5.56 log CFU ml-1 reductions against P. aeruginosa and S. aureus, respectively, whereas samples treated with TB alone showed 2.36 and 2.66 log CFU ml-1 reductions. Anti-biofilm studies confirmed that TB MSN effectively inhibits biofilm formation and production of extracellular polymeric substances by P. aeruginosa and S. aureus.


Assuntos
Biofilmes/efeitos dos fármacos , Fotoquimioterapia/métodos , Pseudomonas aeruginosa/efeitos dos fármacos , Dióxido de Silício/química , Staphylococcus aureus/efeitos dos fármacos , Cloreto de Tolônio/farmacologia , Antibacterianos/farmacologia , Luz , Nanopartículas Metálicas/química , Nanopartículas , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Infecções Estafilocócicas/tratamento farmacológico
6.
Photochem Photobiol Sci ; 18(2): 563-576, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30601523

RESUMO

Catheter-related bloodstream infections (CRBSIs) are one of the leading causes of high morbidity and mortality in hospitalized patients. The proper management, prevention and treatment of CRBSIs rely on the understanding of these highly resistant bacterial infections. The emergence of such a challenge to public health has resulted in the development of an alternative antimicrobial strategy called antimicrobial photodynamic therapy (aPDT). In the presence of a photosensitizer (PS), light of the appropriate wavelength, and molecular oxygen, aPDT generates reactive oxygen species (ROS) which lead to microbial cell death and cell damage. We investigated the enhanced antibacterial and antibiofilm activities of methylene blue conjugated carbon nanotubes (MBCNTs) on biofilms of E. coli and S. aureus using a laser light source at 670 nm with radiant exposure of 58.49 J cm-2. Photodynamic inactivation in test cultures showed 4.86 and 5.55 log10 reductions in E. coli and S. aureus, respectively. Biofilm inhibition assays, cell viability assays and EPS reduction assays showed higher inhibition in S. aureus than in E. coli, suggesting that pronounced ROS generation occurred due to photodynamic therapy in S. aureus. Results from a study into the mechanism of action proved that the cell membrane is the main target for photodynamic inactivation. Comparatively higher photodynamic inactivation was observed in Gram positive bacteria due to the increased production of free radicals inside these cells. From this study, we conclude that MBCNT can be used as a promising nanocomposite for the eradication of dangerous pathogens on medical devices.


Assuntos
Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Azul de Metileno/química , Azul de Metileno/farmacologia , Nanotubos de Carbono/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/efeitos da radiação , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Técnicas de Química Sintética , Escherichia coli/metabolismo , Escherichia coli/fisiologia , Luz , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Azul de Metileno/síntese química , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/metabolismo , Staphylococcus aureus/fisiologia
7.
Photochem Photobiol Sci ; 18(2): 592, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30675604

RESUMO

Correction for 'Synthesis and antimicrobial photodynamic effect of methylene blue conjugated carbon nanotubes on E. coli and S. aureus' by Paramanantham Parasuraman et al., Photochem. Photobiol. Sci., 2019, DOI: 10.1039/c8pp00369f.

8.
Quant Imaging Med Surg ; 8(8): 838-852, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30306063

RESUMO

Cardiovascular diseases (CVDs) are a severely threatening disorder and frequently cause death in industrialized countries, posing critical challenges to modern research and medicine. Molecular imaging has been heralded as the solution to many problems encountered in individuals living with CVD. The use of probes in cardiovascular molecular imaging is causing a paradigmatic shift from regular imaging techniques, to future advanced imaging technologies, which will facilitate the acquisition of vital information at the cellular and molecular level. Advanced imaging for CVDs will help early detection of disease development, allow early therapeutic intervention, and facilitate better understanding of fundamental biological processes. To promote a better understanding of cardiovascular molecular imaging, this article summarizes the current developments in the use of molecular probes, highlighting some of the recent advances in probe design, preparation, and functional modification.

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