scholarly journals In Vitro and In Silico Evaluation of Biological Activity of a New Series of Oxadiazole Compounds Against Esp Gene Expression in Enterococcus faecalis Biofilm

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Sepideh Ghameshlouei ◽  
Nakisa Zarrabi Ahrabi ◽  
Yasin SarveAhrabi

Background: The enterococcal surface protein (Esp) is a high-molecular-weight surface protein of biofilm creating agent in Enterococcus faecalis. Oxadiazoles have a wide range of biological activities. Objective: This research aimed to examine the impact of new oxadiazole derivatives on the expression of Esp, playing an important role in promoting the biofilm formation ability of drug-resistant E. faecalis strains. Method: 1, 3, 4-oxadiazole derivatives were synthesized through a one-step synthesis. E. faecalis strains were collected and isolated from hospitals in Tehran. The antimicrobial properties of the synthesized materials against the isolated strains were investigated. RNA, DNA, and cDNA were extracted, and the relative expression of Esp in E. faecalis isolates was evaluated by real-time PCR. Docking study was performed by AutoDock vina software, and the resulting docking poses were analyzed using Discovery Studio 4.5 Client software. Results: The use of synthesized derivatives changed the Esp expression level in different isolates compared to the control sample. The two compounds containing naphthalene (4f) and methoxyphenyl (4g) caused respectively a 2-fold and a 3-fold decrease in Esp expression compared to the control sample. The compound 4f with the best binding energy among the compounds (-9.2) had the most hydrogen and hydrophobic bonds with the receptor-binding site. Conclusions: 1, 3, 4-oxadiazole derivatives, especially naphthalene and methoxyphenyl, act as inhibitors of bacterial biofilm formation and can be used in the pharmaceutical and biological industries.

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Sedigheh Akbarnezhad Ghareh Lar ◽  
Nakisa Zarrabi Ahrabi ◽  
Yasin SarveAhrabi

Background: Acinetobacter bumanni is one of the most common opportunistic pathogens in health centers that is resistant to many antibiotics due to biofilm production. 1, 3, 4-oxadiazoles have a wide range of biological activities. Objectives: The aim of this research was to examine the impact of new 1, 3, 4-oxadiazole derivatives on the expression of biofilm-associated surface protein (Bap), playing an important role in promoting the biofilm formation ability of A. baumannii strains. Methods: Derivatives of 1, 3, 4-oxadiazole were synthesized through a one-step synthesis. A. baumannii strains were identified and isolated in the laboratory. The antimicrobial properties of the synthesized materials against the isolated strains were investigated. DNA, RNA, and cDNA were extracted, and the relative expression of BAP gene in A. baumannii isolates was evaluated by real-time polymerase chain reaction. Results: The compound with methoxyphenyl functional group with MIC = 62.50 mg/mL had the best inhibitory performance among all derivatives. Also, the combination of 4i reduced the expression of the Bap gene by about 24 times, but it had no effect on the expression of the 16srRNA housekeeping gene. Conclusions: 1, 3, 4-oxadiazole derivatives, especially the methoxyphenyl functional group, act as an inhibitor of bacterial biofilm formation and have the potential to be used in the pharmaceutical and biological industries.


2020 ◽  
Vol 69 (9) ◽  
pp. 1151-1168
Author(s):  
Ahmed Askora ◽  
Mohamed El-Telbany ◽  
Gamal El-Didamony ◽  
Eman Ariny ◽  
Momen Askoura

Introduction. Enterococcus faecalis is a facultative, anaerobic, opportunistic pathogen associated with medical and dental diseases. Bacterial phenotypic traits and pathogenesis are often influenced by lysogeny. Aim. The aim of this study was to characterize both the morphology and complete genome sequences of induced prophages purified from E. faecalis clinical isolates. Methodology. E. faecalis isolates were recovered from the roots of teeth of patients attending an endodontic clinic. The morphological features of isolated phage were characterized using transmission electron microscopy (TEM). DNA sequencing was performed using the Illumina MiSeq platform. Results. TEM indicated that the isolated φEf-vB1 prophage belongs to the family Siphoviridae. The φEf-vB1 prophage was stable over a wide range of temperatures and pH. Sequencing of φEf-vB1 DNA revealed that the phage genome is 37 561 bp in length with a G+C content of 37.6mol% and contained 53 ORFs. Comparison with previously predicted prophage genomes using blast revealed that φEf-vB1 has a high sequence similarity to previously characterized phage genomes. The lysogenic E. faecalis strain exhibited a higher biofilm formation capacity relative to the non-lysogenic strain. Conclusion. The current findings highlight the role of lysogeny in modification of E. faecalis properties and reveal the potential importance of prophages in E. faecalis biology and pathogenesis.


2021 ◽  
Vol 14 (5) ◽  
pp. 467
Author(s):  
Ana Henriques Mota ◽  
Inês Prazeres ◽  
Henrique Mestre ◽  
Andreia Bento-Silva ◽  
Maria João Rodrigues ◽  
...  

Sambucus nigra L. (S. nigra) is a shrub widespread in Europe and western Asia, traditionally used in medicine, that has become popular in recent years as a potential source of a wide range of interesting bioactive compounds. The aim of the present work was to develop a topical S. nigra extract formulation based on ethosomes and thus to support its health claims with scientific evidence. S. nigra extract was prepared by an ultrasound-assisted method and then included in ethosomes. The ethosomes were analyzed in terms of their size, stability over time, morphology, entrapment capacity (EC), extract release profile, stability over time and several biological activities. The prepared ethosomes were indicated to be well defined, presenting sizes around 600 nm. The extract entrapment capacity in ethosomes was 73.9 ± 24.8%, with an interesting slow extract release profile over 24 h. The extract-loaded ethosomes presented collagenase inhibition activity and a very good skin compatibility after human application. This study demonstrates the potential use of S. nigra extract incorporated in ethosomes as a potential cosmeceutical ingredient and on further studies should be performed to better understand the impact of S. nigra compounds on skin care over the time.


2008 ◽  
Vol 74 (11) ◽  
pp. 3551-3558 ◽  
Author(s):  
Rebecca Munk Vejborg ◽  
Per Klemm

ABSTRACT Bacterial biofilm formation on inert surfaces is a significant health and economic problem in a wide range of environmental, industrial, and medical areas. Bacterial adhesion is generally a prerequisite for this colonization process and, thus, represents an attractive target for the development of biofilm-preventive measures. We have previously found that the preconditioning of several different inert materials with an aqueous fish muscle extract, composed primarily of fish muscle α-tropomyosin, significantly discourages bacterial attachment and adhesion to these surfaces. Here, this proteinaceous coating is characterized with regards to its biofilm-reducing properties by using a range of urinary tract infectious isolates with various pathogenic and adhesive properties. The antiadhesive coating significantly reduced or delayed biofilm formation by all these isolates under every condition examined. The biofilm-reducing activity did, however, vary depending on the substratum physicochemical characteristics and the environmental conditions studied. These data illustrate the importance of protein conditioning layers with respect to bacterial biofilm formation and suggest that antiadhesive proteins may offer an attractive measure for reducing or delaying biofilm-associated infections.


2018 ◽  
Vol 11 (3) ◽  
pp. 227-241 ◽  
Author(s):  
Olivier Lesouhaitier ◽  
Thomas Clamens ◽  
Thibaut Rosay ◽  
Florie Desriac ◽  
Mélissande Louis ◽  
...  

Bacterial biofilms constitute a critical problem in hospitals, especially in resuscitation units or for immunocompromised patients, since bacteria embedded in their own matrix are not only protected against antibiotics but also develop resistant variant strains. In the last decade, an original approach to prevent biofilm formation has consisted of studying the antibacterial potential of host communication molecules. Thus, some of these compounds have been identified for their ability to modify the biofilm formation of both Gram-negative and Gram-positive bacteria. In addition to their effect on biofilm production, a detailed study of the mechanism of action of these human hormones on bacterial physiology has allowed the identification of new bacterial pathways involved in biofilm formation. In this review, we focus on the impact of neuropeptidic hormones on bacteria, address some future therapeutic issues, and provide a new view of inter-kingdom communication.


Author(s):  
Ewa Brzozowska ◽  
Anna Pyra ◽  
Krzysztof Pawlik ◽  
Sabina Górska ◽  
Andrzej Gamian

Background: Dual function tail tubular proteins (TTP) belonging to the lytic bacteriophages are the interesting group of biologically active enzymes. Surprisingly, apart from their structural function, they are also polysaccharide hydrolyzes destroying bacterial extracellular components. One of the representatives of this group is TTPB from Klebsiella pneumoniae phage – KP32. TTPB hydrolyzes exopolysaccharide (EPS) of Klebsiella pneumoniae and Enterococcus faecalis strain. This depolymerizing feature was associated with the activity to prevent bacterial biofilm formation. TTPB can inhibit biofilm formation by K. pneumoniae, Enterobacter cloacae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa strains. Moreover, synergistic activity with antibiotic action has been observed, most likely due to depolymerases’ facilitation of contact of antibiotic with bacterial cells. Methods: TTPB was overexpressed in E coli system, purified and tested towards the bacterial strains using agar overlay method. The hydrolytic activity of TTPB was performed using EPSs of K. pneumoniae PCM2713 and E. cloacae ATCC 13047 as the substrates. Next, we determined the reducing sugar (RS) levels in the TTPB/EPS mixtures, regarding the RS amount obtained after acidic hydrolysis. The antibiofilm activity of TTPB has been set down on bacterial biofilm using a biochemical method. Finally, we have demonstrated the synergistic activity of TTPB with kanamycin. Results: For the first time, the hydrolytic activity of TTPB towards bacterial EPSs has been shown. TTPB releases about a half of the whole RS amount of EPSs belonging to K. pneumoniae PCM 2713 and E. cloacae ATCC 13047 strains. 1.12 µM of the phage protein reduces biofilm of both strains by over 60%. Destroying the bacterial biofilm the phage protein improves the antibiotic action increasing kanamycin effectiveness up to four times.


1998 ◽  
Vol 42 (4) ◽  
pp. 895-898 ◽  
Author(s):  
Silvia Schwank ◽  
Zarko Rajacic ◽  
Werner Zimmerli ◽  
Jürg Blaser

ABSTRACT The impact of bacterial adherence on antibiotic activity was analyzed with two isogenic strains of Staphylococcus epidermidis that differ in the features of their in vitro biofilm formation. The eradication of bacteria adhering to glass beads by amikacin, levofloxacin, rifampin, or teicoplanin was studied in an animal model and in a pharmacokinetically matched in vitro model. The features of S. epidermidis RP62A that allowed it to grow on surfaces in multiple layers promoted phenotypic resistance to antibiotic treatment, whereas strain M7 failed to accumulate, despite initial adherence on surfaces and growth in suspension similar to those for RP62A. Biofilms of S. epidermidis M7 were better eradicated than those of strain RP62A in vitro (46 versus 31%;P < 0.05) as well as in the animal model (39 versus 9%; P < 0.01).


2020 ◽  
Author(s):  
Bin Cao ◽  
Yidan Hu ◽  
Xiaobo Liu ◽  
Aloysius Teng ◽  
Ji-Dong Gu

&lt;p&gt;Biofilm as a living catalysts has been exploited for the production of biofuels and bioelectricity in microbial fuel cells (MFCs) as well as in the synthesis of bulk and fine chemicals. However, the structure and activity of biofilms are highly dynamic and heterogeneous, which makes the control of biofilm-mediated bioprocesses challenging and limits their application in industrial biotechnology. Efficient biofilm-mediated biocatalysis requires the modulation of biofilm formation. In a wide range of bacteria, the development of biofilm is subject to a signal cascade regulated by the intracellular levels of secondary messenger bis-(3'-5') cyclic dimeric guanosine monophosphate (c-di-GMP). Typically, an increase in c-di-GMP level enhances biofilm formation while a decrease in c-di-GMP level leads to biofilm dispersal. Intracellular levels of c-di-GMP are modulated in response to internal and environmental cues, which is achieved by the activities of diguanylate cyclases (DGCs, c-di-GMP synthases) and phosphodiesterases (PDEs, c-di-GMP hydrolases). Hence, biofilm formation can be modulated by controlling the expression of genes encoding DGCs or PDEs using chemical inducers.&lt;/p&gt; &lt;p&gt;For biofilm-mediated biocatalysis for chemicals synthesis, it would be desirable if chemical inducers could be avoided for modulating biofilm formation. Light as a non-invasive stimulus is such an attractive inducer, which can offer a higher spatiotemporal resolution in the regulation of biological activities. Several light-responsive regulatory modules have been reported for protein degradation, protein&amp;#8211;protein interactions and gene expression. In particular, the near infrared (NIR) light (680&amp;#8211;880 nm) is an attractive inducer for the photocontrol of biological activities because of its deep penetration and non-toxicity. In this study, we engineered a near infrared (NIR) light-responsive, tryptophan-producing &lt;em&gt;Escherichia coli&lt;/em&gt; biofilm by introducing a NIR light-responsive DGC and the genes encoding tryptophan synthase (TrpAB). Biofilm formation of the engineered &lt;em&gt;E. coli&lt;/em&gt; could be modulated by NIR light through manipulation of the intracellular c-di-GMP concentration and the biotransformation of indole and serine into tryptophan was catalyzed by TrpAB. The engineered catalytic biofilm overcame the inhibition of indole on biofilm formation by E. coli and reduced the reverse reaction from tryptophan to indole. By applying the engineered biofilm to catalyze the biotransformation of indole into tryptophan in submerged biofilm reactors, we showed that NIR light enhanced biofilm formation to result in 30% increase in tryptophan yield. This demonstrates the feasibility of applying light to modulate the catalytic biofilm formation and performance for chemical production in bioreactors. The optogenetic approach for modulating catalytic biofilm we have demonstrated here would allow the wide application for further biofilm-mediated biocatalysis.&lt;/p&gt;


2004 ◽  
Vol 72 (10) ◽  
pp. 6032-6039 ◽  
Author(s):  
Preeti M. Tendolkar ◽  
Arto S. Baghdayan ◽  
Michael S. Gilmore ◽  
Nathan Shankar

ABSTRACT Enterococci play a dual role in human ecology. They serve as commensal organisms of the gastrointestinal tract and are also leading causes of multiple antibiotic-resistant hospital-acquired infection. Many nosocomial infections result from the ability of microorganisms to form biofilms. The molecular mechanisms involved in enterococcal biofilm formation are only now beginning to be understood. Enterococcal surface protein, Esp, has been reported to contribute to biofilm formation by Enterococcus faecalis. Recent studies have shown that enterococci form biofilms independently of Esp expression. To precisely determine what role Esp plays in E. faecalis biofilm formation, Esp was expressed on the cell surface of genetically well-defined, natively Esp-deficient strains, and isogenic Esp-positive and Esp-deficient strains were compared for their biofilm-forming ability. The results show that Esp expression leads to a significant increase in biofilm formation, irrespective of the strain tested. The contribution of Esp to biofilm formation was found to be most pronounced in the presence of 0.5% (wt/vol) or greater glucose. These results unambiguously define Esp as a key contributor to the ability of E. faecalis to form biofilms.


2001 ◽  
Vol 67 (10) ◽  
pp. 4538-4545 ◽  
Author(s):  
Alejandro Toledo-Arana ◽  
Jaione Valle ◽  
Cristina Solano ◽  
Marı́a Jesús Arrizubieta ◽  
Carme Cucarella ◽  
...  

ABSTRACT The enterococcal surface protein, Esp, is a high-molecular-weight surface protein of unknown function whose frequency is significantly increased among infection-derived Enterococcus faecalisisolates. In this work, a global structural similarity was found between Bap, a biofilm-associated protein of Staphylococcus aureus, and Esp. Analysis of the relationship between the presence of the Esp-encoding gene (esp) and the biofilm formation capacity in E. faecalis demonstrated that the presence of the esp gene is highly associated (P < 0.0001) with the capacity of E. faecalis to form a biofilm on a polystyrene surface, since 93.5% of the E. faecalis esp-positive isolates were capable of forming a biofilm. Moreover, none of the E. faecalis esp-deficient isolates were biofilm producers. Depending on theE. faecalis isolate, insertional mutagenesis ofesp caused either a complete loss of the biofilm formation phenotype or no apparent phenotypic defect. Complementation studies revealed that Esp expression in an E. faecalis esp-deficient strain promoted primary attachment and biofilm formation on polystyrene and polyvinyl chloride plastic from urine collection bags. Together, these results demonstrate that (i) biofilm formation capacity is widespread among clinical E. faecalis isolates, (ii) the biofilm formation capacity is restricted to the E. faecalis strains harboringesp, and (iii) Esp promotes primary attachment and biofilm formation of E. faecalis on abiotic surfaces.


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