scholarly journals Biofunctionalization of Poly(lactide-co-glycolic acid) Using Potent NorA Efflux Pump Inhibitors Immobilized on Nanometric Alpha-Zirconium Phosphate to Reduce Biofilm Formation

Materials ◽  
2021 ◽  
Vol 14 (3) ◽  
pp. 670
Author(s):  
Monica Pica ◽  
Nicla Messere ◽  
Tommaso Felicetti ◽  
Stefano Sabatini ◽  
Donatella Pietrella ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Zirconium Phosphate ◽  
Glycolic Acid ◽  
Efflux Pump ◽  
Composite Films ◽  
Homogeneous Distribution ◽  
X Ray Diffraction ◽  
Implanted Medical Devices ◽  
Efflux Pump Inhibitors ◽  
Biofilm Inhibitor

Polymeric composites, where bioactive species are immobilized on inorganic nanostructured matrix, have received considerable attention as surfaces able to reduce bacterial adherence, colonization, and biofilm formation in implanted medical devices. In this work, potent in-house S. aureus NorA efflux pump inhibitors (EPIs), belonging to the 2-phenylquinoline class, were immobilized on nanometric alpha-zirconium phosphate (ZrP) taking into advantage of acid-base or intercalation reactions. The ZrP/EPI were used as filler of poly(lactide-co-glycolic acid) (PLGA) to obtain film composites with a homogeneous distribution of the ZrP/EPI fillers. As reference, PLGA films loaded with ZrP intercalated with thioridazine (TZ), that is recognized as both a NorA and biofilm inhibitor, and with the antibiotic ciprofloxacin (CPX) were prepared. Composite films were characterized by X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis. The ability of the composite films, containing ZrP/EPI, to inhibit biofilm formation was tested on Staphylococcus aureus ATCC 29213 and Staphylococcus epidermidis ATCC 12228, and it was compared with that of the composite loaded with ZrP/TZ. Finally, the antibacterial activity of CPX intercalated in ZrP was evaluated when used in combination with ZrP/EPI in the PLGA films.

scholarly journals Investigation on the effect of known potent S. aureus NorA efflux pump inhibitors on the staphylococcal biofilm formation

RSC Advances ◽  
2017 ◽  
Vol 7 (59) ◽  
pp. 37007-37014 ◽  
Author(s):  
Stefano Sabatini ◽  
Miranda Piccioni ◽  
Tommaso Felicetti ◽  
Stefania De Marco ◽  
Giuseppe Manfroni ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Efflux Pump Inhibitors

The emergence of multidrug resistant microorganisms has triggered the impending need of developing effective antibacterial strategies.

scholarly journals Inactivation of Efflux Pumps Abolishes Bacterial Biofilm Formation

2008 ◽  
Vol 74 (23) ◽  
pp. 7376-7382 ◽  
Author(s):  
Malin Kvist ◽  
Viktoria Hancock ◽  
Per Klemm
Keyword(s):  
Health Care ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Bacterial Biofilm ◽  
Bacterial Biofilms ◽  
Toxic Substances ◽  
Highly Active ◽  
Efflux Pump Inhibitors ◽  
New Treatments

ABSTRACT Bacterial biofilms cause numerous problems in health care and industry; notably, biofilms are associated with a large number of infections. Biofilm-dwelling bacteria are particularly resistant to antibiotics, making it hard to eradicate biofilm-associated infections. Bacteria rely on efflux pumps to get rid of toxic substances. We discovered that efflux pumps are highly active in bacterial biofilms, thus making efflux pumps attractive targets for antibiofilm measures. A number of efflux pump inhibitors (EPIs) are known. EPIs were shown to reduce biofilm formation, and in combination they could abolish biofilm formation completely. Also, EPIs were able to block the antibiotic tolerance of biofilms. The results of this feasibility study might pave the way for new treatments for biofilm-related infections and may be exploited for prevention of biofilms in general.

scholarly journals Cotton Cellulose-CdTe Quantum Dots Composite Films with Inhibition of Biofilm-Forming S. aureus

Fibers ◽  
2019 ◽  
Vol 7 (6) ◽  
pp. 57 ◽  
Author(s):  
Rohan S. Dassanayake ◽  
Poorna T. Wansapura ◽  
Phat Tran ◽  
Abdul Hamood ◽  
Noureddine Abidi
Keyword(s):  
Quantum Dots ◽  
Composite Film ◽  
Biofilm Formation ◽  
Biomedical Applications ◽  
Composite Films ◽  
X Ray Diffraction ◽  
Promising Candidate ◽  
X Ray ◽  
Cdte Qds

A cellulose-cadmium (Cd)-tellurium (TE) quantum dots (QDs) composite film was successfully synthesized by incorporating CdTe QDs onto a cellulose matrix derived from waste cotton linters. Cellulose-CdTe QDs composite film was characterized by field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and X-ray diffraction (XRD). The antibacterial activity of the prepared composite film was investigated using the multidrug-resistance (MTR) Staphylococcus aureus bacteria. In vitro antibacterial assays demonstrated that CdTe QDs composite film can efficiently inhibit biofilm formation. Our results showed that the cellulose-CdTe QDs composite film is a promising candidate for biomedical applications including wound dressing, medical instruments, burn treatments, implants, and other biotechnology fields.

scholarly journals Antifungal Azoles as Tetracycline Resistance-Modifiers in Staphylococcus aureus

2021 ◽  
Author(s):  
Nisha Mahey ◽  
Rushikesh Tambat ◽  
Dipesh Kumar Verma ◽  
Nishtha Chandal ◽  
Krishan Gopal Thakur ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Silico ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Major Facilitator Superfamily ◽  
Efflux Pump Inhibitors ◽  
Approved Drugs ◽  
Major Facilitator

Staphylococcus aureus has developed resistance to antimicrobials since its first use. The S. aureus major facilitator superfamily (MFS) efflux pump Tet(K) contributes to resistance to tetracyclines. The efflux pump diminishes antibiotic accumulation, and biofilm hampers the diffusion of antibiotics. None of the currently known compounds have been approved as efflux pump inhibitors (EPIs) for clinical use. In the current study, we screened clinically approved drugs for possible Tet(K) efflux pump inhibition. In silico docking followed by in vitro checkerboard assays, we identified five azoles (the fungal ergosterol synthesis inhibitors) showing the putative EPI-like potential with a fractional inhibitory concentration index of ≤0.5, indicating synergism. The functionality of the azoles was confirmed using ethidium bromide (EtBr) accumulation and efflux inhibition assays. In time-kill kinetics, the combination treatment with butoconazole engendered a marked increase in the bactericidal capacity of tetracycline. When assessing the off-target effects of the azoles, we observed no disruption of bacterial membrane permeability and polarization. Finally, the combination of azoles with tetracycline led to a significant eradication of preformed mature biofilms. This study is the primary representation of azoles that can be repurposed as putative Tet(K) EPIs and to reduce biofilm formation at clinically relevant concentrations. IMPORTANCE Staphylococcus aureus use efflux pumps to transport antibiotics out of the cell and thus increase the dosage at which they endure antibiotics. Also, efflux pumps play a role in biofilm formation by the excretion of extracellular matrix molecules. One way to combat these pathogens may be to reduce the activity of efflux pumps and thereby increase pathogen sensitivity to existing antibiotics. We describe the in silico-based screen of clinically approved drugs that identified antifungal azoles inhibiting Tet(K); a pump belongs to the Major Facilitator Superfamily and shows that these compounds bind to and block the activity of the Tet(K) pump. Azoles enhanced the susceptibility of tetracycline against S. aureus and its methicillin-resistant strains. The combination of azoles with tetracycline led to a significant reduction in preformed biofilms. Repurposing of approved drugs may help solve the classical toxicity issues related to efflux pump inhibitors.

Screening of Natural Products and Derivatives for the Identification of RND Efflux Pump Inhibitors

2016 ◽  
Vol 19 (9) ◽  
pp. 705-713 ◽  
Author(s):  
Debarati Choudhury ◽  
Anupam Talukdar ◽  
Pankaj Chetia ◽  
Amitabha Bhattacharjee ◽  
Manabendra Choudhury
Keyword(s):  
Natural Products ◽  
Efflux Pump ◽  
Rnd Efflux Pump ◽  
Efflux Pump Inhibitors

Virtual Screening for Novel Staphylococcus Aureus NorA Efflux Pump Inhibitors From Natural Products

2015 ◽  
Vol 11 (2) ◽  
pp. 135-155 ◽  
Author(s):  
Khac-Minh Thai ◽  
Trieu-Du Ngo ◽  
Thien-Vy Phan ◽  
Thanh-Dao Tran ◽  
Ngoc-Vinh Nguyen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Natural Products ◽  
Virtual Screening ◽  
Efflux Pump ◽  
Efflux Pump Inhibitors

scholarly journals From quinoline to quinazoline‐based S. aureus NorA efflux pump inhibitors by coupling focused scaffold hopping approach and pharmacophore search

ChemMedChem ◽  
2021 ◽  
Author(s):  
Nicholas Cedraro ◽  
Rolando Cannalire ◽  
Andrea Astolfi ◽  
Gianmarco Mangiaterra ◽  
Tommaso Felicetti ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Scaffold Hopping ◽  
Efflux Pump Inhibitors

scholarly journals Effect of Titanium Dioxide Nanoparticles on the Expression of Efflux Pump and Quorum-Sensing Genes in MDR Pseudomonas aeruginosa Isolates

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 625
Author(s):  
Fatma Y. Ahmed ◽  
Usama Farghaly Aly ◽  
Rehab Mahmoud Abd El-Baky ◽  
Nancy G. F. M. Waly
Keyword(s):  
Titanium Dioxide ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Titanium Dioxide Nanoparticles ◽  
Sol Gel ◽  
Efflux Pumps ◽  
Antibiofilm Activity ◽  
The Impact

Most of the infections caused by multi-drug resistant (MDR) P. aeruginosa strains are extremely difficult to be treated with conventional antibiotics. Biofilm formation and efflux pumps are recognized as the major antibiotic resistance mechanisms in MDR P. aeruginosa. Biofilm formation by P. aeruginosa depends mainly on the cell-to-cell communication quorum-sensing (QS) systems. Titanium dioxide nanoparticles (TDN) have been used as antimicrobial agents against several microorganisms but have not been reported as an anti-QS agent. This study aims to evaluate the impact of titanium dioxide nanoparticles (TDN) on QS and efflux pump genes expression in MDR P. aeruginosa isolates. The antimicrobial susceptibility of 25 P. aeruginosa isolates were performed by Kirby–Bauer disc diffusion. Titanium dioxide nanoparticles (TDN) were prepared by the sol gel method and characterized by different techniques (DLS, HR-TEM, XRD, and FTIR). The expression of efflux pumps in the MDR isolates was detected by the determination of MICs of different antibiotics in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP). Biofilm formation and the antibiofilm activity of TDN were determined using the tissue culture plate method. The effects of TDN on the expression of QS genes and efflux pump genes were tested using real-time polymerase chain reaction (RT-PCR). The average size of the TDNs was 64.77 nm. It was found that TDN showed a significant reduction in biofilm formation (96%) and represented superior antibacterial activity against P. aeruginosa strains in comparison to titanium dioxide powder. In addition, the use of TDN alone or in combination with antibiotics resulted in significant downregulation of the efflux pump genes (MexY, MexB, MexA) and QS-regulated genes (lasR, lasI, rhll, rhlR, pqsA, pqsR) in comparison to the untreated isolate. TDN can increase the therapeutic efficacy of traditional antibiotics by affecting efflux pump expression and quorum-sensing genes controlling biofilm production.

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