Browsing by Author "Unlu, Sezin"

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Antibacterial, Antifungal and Antibiofilm Activity of Methylglyoxal: A Phytochemical from Manuka Honey Metilglioksalin Antibakteriyel, Antifungal ve Antibiyofilm Aktivitesi: Manuka Balindan Bir Fitokimyasal
(2021) Uskudar-Guclu, Aylin; Simsek, Derya; Ata-Vural, Ilgin; Unlu, Sezin; Basustaoglu, Ahmet; 0000-0002-1872-028X; AAU-6196-2020
Introduction: Honey has been known for its ability to promote wound healing for a long time. It is utilized for several skin and soft tissue infections caused by a wide range of microorganisms due to its antimicrobial property. Methylglyoxal (MGO), the unique antibacterial compound contained by Manuka honey, is believed as the reason for the antimicrobial activity of Manuka honey. This study aims to identify the antibacterial, antifungal and anti-adherent activity of MGO in changing concentrations and determine the viable number of bacteria and fungi in biofilm after the treatment of MGO. Materials and Methods: Antibacterial and antifungal activity of MGO was determined by broth microdilution method for identifying minimum inhibitory and bactericidal and fungicidal concentrations (MIC, MBC and MFC, respectively). Percentage of biofilm formation inhibition and the number of viable microorganisms in biofilm after the MGO treatment was determined by the colony-forming unit method. Results: Minimum inhibitory concentration values for the bacterial strains ranged from 0.0078 to 0.125010 (v/v), while MBC ranged from 0.0312 to 2010 (v/v). Among fungi, MIC and MFC values were higher than those for tested bacterial strains; MIC values ranged from 0.0156 to 1010 (v/v), while MFC values ranged from 0.0625 to 2010 (v/v). Methylglyoxal was able to prevent biofilm formation in the all tested biofilm forming isolates. Number of viable bacteria, even in the sub-inhibitory doses of MGO, reduced remarkably. Conclusion: Unique compound of Manuka honey, MGO, exerts significant antimicrobial and antibiofilm activity against clinically important strains of both bacteria and fungi which may be utilized for the search of promising alternatives for antibiotics and may lead to combat antibiotic resistance.
Co-existence of Multiple Resistance Mechanisms in Clinical Isolates of Carbapenem-Resistant Pseudomonas Aeruginosa
(2022) Uskudar-Guclu, Aylin; Mirza, Hasan Cenk; Unlu, Sezin; https://orcid.org/0000-0002-1872-028X; https://orcid.org/0000-0002-8853-3893; AAU-6196-2020; F-1232-2015
Introduction: Multidrug resistance phenotype of Pseudomonas aeruginosa utilizes several resistant mechanisms to overcome the action of antibiotics. This phenotype is caused by several resistance mechanisms or a combination of thereof. This study aimed to evaluate various resistance mechanisms by phenotypic methods. Materials and Methods: Carbapenem-resistant P. aeruginosa were included in this study. Antimicrobial resistance mechanisms such as efflux pump activity, reduced outer membrane permeability (OMP), various beta-lactamase activities, and biofilm formation ability of clinical P aeruginosa isolates were determined by phenotypic methods. Results: Of the P aeruginosa isolates, 33.7% (n= 33/98) had a positive efflux pump activity. The co-existence of positive efflux pump activity and Metallo beta-lactamase (MBL) production was detected in 30.3% (10/33) of the isolates. In 34.7% of the clinical P. aeruginosa isolates, reduced OMP was detected and 70.6% of them were also biofilm producers. Totally 21.4% (21/98) of P aeruginosa isolates were evaluated as extended-spectrum beta-lactamase (ESBL) positive. AmpC beta-lactamase was detected in 15.3% (n= 15/98) of the clinical P. aeruginosa isolates. MBL activity was detected in 33.7% (n= 33/98) of the clinical P. aeruginosa isolates. Of the MBL-positive isolates, 69.7% were biofilm producers. The co-existence of MBL and reduced OMP was detected in 36.4% (n= 12/33). Conclusion: High resistance of P. aeruginosa was attributed to several resistance mechanisms or a combination of thereof. This infections caused by multidrug-resistant (MDR) P. aeruginosa are difficult to treat due to the co-existence of different resistance mechanisms.
The Impacts of 13 Novel Mutations of SARS-Cov-2 on Protein Dynamics: in Silico Analysis From Turkey
(2022) Unlu, Sezin; Uskudar-Guclu, Aylin; Cela, Isli; 37520163
SARS-CoV-2 inherits a high rate of mutations making it better suited to the host since its fundamental role in evolution is to provide diversity into the genome. This research aims to identify variations in Turkish isolates and predict their impacts on proteins. To identify novel variations and predict their impacts on protein dynamics, in silico methodology was used. The 411 sequences from Turkey were analysed. Secondary structure prediction by Garnier-Osguthorpe-Robson (GOR) was used. To find the effects of identified Spike mutations on protein dynamics, the SARS-CoV-2 structures (PDB:6VYB, 6M0J) were uploaded and predicted by Cutoff Scanning Matrix (mCSM), DynaMut and MutaBind2. To understand the effects of these mutations on Spike protein molecular dynamics (MD) simulation was employed. Turkish sequences were aligned with sequences worldwide by MUSCLE, and phylogenetic analysis was performed via MegaX. The 13 novel mutations were identified, and six of them belong to spike glycoprotein. Ten of these variations revealed alteration in the secondary structure of the protein. Differences of free energy between the reference sequence and six mutants were found below zero for each of six isolates, demonstrating these variations have stabilizing effects on protein structure. Differences in vibrational entropy calculation revealed that three variants have rigidification, while the other three have a flexibility effect. MD simulation revealed that point mutations in spike glycoprotein and RBD:ACE-2 complex cause changes in protein dynamics compared to the wild-type, suggesting possible alterations in binding affinity. The phylogenetic analysis showed Turkish sequences distributed throughout the tree, revealing multiple entrances to Turkey.
Predominant Mutations of SARS-CoV-2: Their Geographical Distribution and Potential Consequences
(2021) Unlu, Sezin; Uskudar Guclu, Aylin; Basustaoglu, Ahmet; 0000-0001-7490-7981; 0000-0002-1872-028X; AAQ-4702-2021; AAU-6196-2020
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) emerged in late December 2019 in Wuhan, China. More than 83 million people have been infected, and more than 1.8 million people have died, as reported to the World Health Organization on the 3rd of January, 2021. Analysis of genetic variations is critical for understanding the spreading pattern of SARS-CoV-2 across several countries. This review aimed to gather information about the prominent mutations of SARS-CoV-2 by analyzing the origin, viral pathogenesis, and mutation rate. Moreover, we concluded their potential impacts on SARS-CoV-2 therapeutics. Mutations in the spike protein (D614G, N501Y, E484K, A222V, S477N, and G485R), ORF1ab (P323L, N628N, Y455Y, A97V, and F106F), nucleocapsid protein (R203K and G204R), ORF8 (L84S), and ORF3a (Q57H and G251V) were examined in this review by analyzing relevant articles from the beginning of the current pandemic to the most recent date. A detailed analysis of articles demonstrates that D614G is the major variation distributed globally, and its frequency increased rapidly from early in March, followed by several other variations in either spike or different proteins. In addition, it was seen that the currently circulating N501Y and E484K variants revealed a public concern regarding vaccines' efficacy. Investigation of variations of SARS-CoV-2 would lead to understanding their potential mechanism of action against SARS-CoV-2, thereby suggesting suitable therapeutics. Several mechanisms were suggested to have a role in SARS-CoV-2 mutation rate and evolution. Possible therapeutics and vaccines against SARS-CoV-2 were proposed.