Papers by Safak Ermertcan
bioRxiv (Cold Spring Harbor Laboratory), Dec 31, 2023
Antibiotic resistance poses a global health crisis, limiting the efficacy of available therapeuti... more Antibiotic resistance poses a global health crisis, limiting the efficacy of available therapeutic agents and hindering the development of new antibiotics. The pharmaceutical industry's waning interest in antibiotic production further exacerbates this challenge. Addressing antibiotic resistance demands innovative solutions. Here, we explore the application of CRISPR-Cas-based antimicrobials as a pioneering approach to combat multidrug resistance. Our study focuses on the methicillin-resistant clinical Staphylococcus aureus (MRSA), a significant clinical threat. Utilizing CRISPR/Cas9 technology, we aimed to concurrently target methicillin (mecA), gentamicin (aacA), and ciprofloxacin (grlA, grlB) resistance genes, thereby altering the resistance profile and enhancing sensitivity to antibiotics. We engineered CRISPR plasmids containing sgRNAs specific to the target regions, which were subsequently electroporated into MRSA strains. Real-time Polymerase Chain Reaction (RT-PCR) assessed changes in resistance gene expression, while disk diffusion and broth microdilution methods determined alterations in resistance status. Western blotting analyzed changes in PBP2a expression, and Sanger sequence analysis confirmed mutations in target regions. Results revealed a statistically significant 1.5-fold decrease in mecA gene expression, 5.5-fold decrease in grlA gene, 6-fold decrease in grlB gene, and 4-fold decrease in aacA gene compared to the wild type strain, as determined by RT-PCR. Antibiotic susceptibility tests demonstrated the suppression of mecA, grlA, grlB, and aacA genes, resulting in the reversal of resistance to beta-lactam, quinolone, and aminoglycoside antibiotics. Western blot analysis showed 70% decrease in PBP2a expression, indicating the breakdown of beta-lactam resistance. Sanger sequence analysis confirmed point mutations in grlB and aacA genes, along with three-base mutations in grlA and mecA genes. Our findings underscore the potential of CRISPR/Cas9 technology to mitigate antibiotic resistance, offering a transformative strategy to restore the efficacy of existing antibiotics in the face of multidrug-resistant pathogens. .
PubMed, Sep 1, 2009
We investigated the linezolid susceptibility of Mycobacterium tuberculosis strains isolated from ... more We investigated the linezolid susceptibility of Mycobacterium tuberculosis strains isolated from a tertiary care hospital in Izmir. A total of 67 M. tuberculosis strains (33 multidrug-resistant [MDR] and 34 non-MDR) were isolated and identified by the Tuberculosis Laboratory, Department of Microbiology and Clinical Microbiology, Faculty of Medicine, Ege University. The activity of linezolid was studied by the standard agar proportion method. For all of the strains, the MIC range was 0.06-1 mg/L, and the MIC(50) and MIC(90) values were 0.5 mg/L. No differences were observed between the MDR and non-MDR isolates. In general, linezolid was found to be effective for both the non-MDR and MDR M. tuberculosis strains.
Journal of the Turkish Chemical Society Section A: Chemistry
Herein we synthesized 6 new N,N-disubstituted taurinamidobenzensulfonamide derivatives and charac... more Herein we synthesized 6 new N,N-disubstituted taurinamidobenzensulfonamide derivatives and characterized their structures by means of 1H and 13C NMR, HR-MS analysis. In addition, their in vitro antibacterial and antifungal activities were tested against two gram-positive, two gram-negative bacteria, and two fungal strains by using broth microdilution method. Compounds 1 (methoxy substitution) and 2 (methyl substitution) displayed the best antibacterial activity against Escherichia coli and Staphylococcus aureus, respectively. E. faecalis was affected by compounds 1, 2, 4, and 6, becoming the most susceptible pathogen compared to other tested bacterial and fungal strains. Interestingly, changing fluoro atom in compound 6 with the chloro atom, as in compound 5, deteriorated the antibacterial activity against all bacterial strains. As a result, these results provide us to investigate the relationship between structural changes and antibacterial/antifungal activity, which can be further...
NOVA Science Publishers Inc., 2010
Turkish Journal of Infection, 2000
Bu çalışmada Staphylococcus aureus kökenleri üzerine fusidik asidin antimikrobiyal etkinliğinin d... more Bu çalışmada Staphylococcus aureus kökenleri üzerine fusidik asidin antimikrobiyal etkinliğinin disk difüzyon ve mikrodilüsyon yöntemleri ile araştırılması amaçlandı. Toplam 140 S. aureus kökeninde metisilin direnci belirlendikten sonra bu kökenlerin fusidik aside karşı duyarlılıkları araştırıldı. Minimum inhibisyon konsantrasyonu (MİK) ve inhibisyon zon çapları Comite de l'Antibiogramme de la societe française de Microbiologie kriterlerine göre belirlendi. Metisilin direnci % 6 olan bu kökenlerin fusidik aside duyarlılık oranı %98 olarak saptandı. Sadece üç kökenin (% 2) fusidik aside orta derecede duyarlı olduğu görüldü. Bu çalışmanın sonucuna göre, stafilokok infeksiyonlarında fusidik asit etkili bir antibiyotiktir.In this study, the antimicrobial activity of fusidic acid on Staphylocccus aureus strains was investigated by disk diffusion and microdilution methods. the methicillin resistance and then fusidic acid susceptibility were determined in 140 S. aureus strains. To determine the diameter of inhibition zones and minimum inhibition concentration (MIC) range, the criteria of Comite' de l'Antibiogramme de la Societe Française de Microbiologie were used. the rate of susceptibility to fusidic acid, in which methicillin resistance was 6 %, was 98 %. of these strains only three (2 %) were found to be intermediate susceptible. It is concluded that fusidic acid is an effective antibiotic against staphylococci
1992 yılında yapılan bir çalışmada, fusidik asit ve siprofloksasin arasında antibakteriyel antago... more 1992 yılında yapılan bir çalışmada, fusidik asit ve siprofloksasin arasında antibakteriyel antagonizma olduğu saptanmıştır. Bu çalışmadan esinlenerek, Staphylococcus aureus kökenleri üzerinde fusidik asit ve siprofloksasin arasındaki antibakteriyel antagonizmanın varlığı disk yakınlaştırma yöntemi ile araştırıldı. Toplam 131 S. Aureus kökeninin 24'ünde (%18) fusidik asit ve siprofloksasin arasında antagonizma saptanırken, bir kökende her iki antibiyotik arasında sinerjizm olduğu görüldü. Bu antagonistik etkinin nedeni ve ne gibi klinik sonuçlar doğuracağı kesin olarak bilinmemektedir. Bu nedenle gittikçe sayısı artan florokinolon grubu antibiyotiklerle diğer antimikrobiyal ajanlar arasındaki etkileşimin açıklanması için çok sayıda çalışmaya gereksinim vardır.In a study made in 1992, it was determined that there was an antibacterial antagonism between fusidic acid and ciprofloxacin. Inspired by this study, antibacterial antagonism between fusidic acid and ciprofloxacin in Staphylococcus aureus strains was investigated using disk approximation test. The study showed that in 24 (18%) out of 131 S. Aureus strains there was an antagonism between fusidic acid and ciprofloxacin, while synergism was determined between both antibiotics in one of the strains. The reason for this antagonistic effect and its clinical implications are not known. To explain the interaction between the increasing number of fluoroquinolones and other antimicrobial agents, further studies on the subject are needed
Tuberkuloz ve Toraks, 2018
In vitro effects of ciprofloxacin, levofloxacin and Moxifloxacin on Mycobacterium tuberculosis is... more In vitro effects of ciprofloxacin, levofloxacin and Moxifloxacin on Mycobacterium tuberculosis isolates Introduction: Increased tuberculosis prevalence, and isolation of multidrug resistant (MDR) Mycobacterium tuberculosis strains frequently as causative organisms from tuberculosis infections are resulted in increasing need of new anti-tuberculosis drugs. Nowadays, fluoroquinolones known to have fewer side effects than the other drugs used in treatment of tuberculosis are sometimes assessed even as first-line anti-tuberculosis drugs due to their in vitro and in vivo strong activity. It was aimed in this study to investigate phenotypically the fluoroquinolone susceptibility in MDR and non-MDR M. tuberculosis isolates. Materials and Methods: A total of 126 MDR and non-MDR M. tuberculosis isolates from mycobacteriology laboratory of two hospitals in the Aegean Region of Turkey were included in the study. Ciprofloxacin (CIP), levofloxacin (LEV) and moxifloxacin (MXF) susceptibilities were assessed by agar proportion method according to the Clinical and Laboratory Standards Institute (CLSI) recommendations.
Saudi Medical Journal, May 1, 2007
To investigate the post-antibiotic effect (PAE) of linezolid against methicillin-resistant and -s... more To investigate the post-antibiotic effect (PAE) of linezolid against methicillin-resistant and -susceptible staphylococci, vancomycin-resistant and -susceptible enterococci. Clinical strains of Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis) and Enterococcus faecalis (E. faecalis) were isolated from hospitalized patients at Ege University Medical Faculty Hospital between June and September 2005. This study was made between September and December 2005. The PAE of linezolid was determined at the minimum inhibitory concentration (MIC) and 4 times the MIC concentrations for 60 minutes in Mueller-Hinton Broth (MHB). The duration of the PAE was obtained by following the recovery of bacterial growth in antibiotic free MHB measured colony forming units on Mueller-Hinton agar. All the straines were susceptible to linezolid. The PAE was greater at 4 times the MIC (0.5 - 2.4 hours) that at the MIC (0 - 1.7 hours) for linezolid against all organisms tested. The PAE for linezolid was slightly higher against E. faecalis strains than other organisms. In this study, it was demonstrated that linezolid had a moderate in vitro PAE against S. aureus, S. epidermidis and E.faecalis strains.
Turkish Journal of Medical Sciences, Apr 5, 2004
The present study aimed to determine the correlation between the bactericidal activity of vancomy... more The present study aimed to determine the correlation between the bactericidal activity of vancomycin and quinupristin/dalfopristin (Q/D) on Staphylococcus aureus isolates and their minimal inhibition concentrations. The in-vitro susceptibilities of the 99 S. aureus isolates to vancomycin and Q/D were investigated by agar dilution. Thirty methicillin-resistant S. aureus (MRSA) and 30 methicillin-susceptible S. aureus (MSSA) vancomycin and Q/D susceptible isolates were involved in time-kill studies. While both MRSA and MSSA isolates were susceptible to vancomycin, 96% of both isolates were determined as susceptible to Q/D. In the time-kill test, after 6 h of incubation vancomycin exhibited a bactericidal activity of 90% on MRSA and 100% on MSSA isolates. On the other hand, in the same incubation period Q/D was 47% and 93% bactericidal for MRSA and MSSA isolates, respectively. After 24 h of incubation, while vancomycin was bactericidal for all MRSA and MSSA isolates, Q/D exhibited a bactericidal activity of 93% on MRSA isolates and 97% on MSSA isolates.
The West Indian medical journal, 2008
The purpose of this study was to determine the synergistic activity of amikacin/ertapenem, fluoro... more The purpose of this study was to determine the synergistic activity of amikacin/ertapenem, fluoroquinolones (ciprofloxacin and levofloxacin)/ertapenem and amikacin/fluoroquinolones combinations against resistant nosocomial pathogens. Time-kill studies were performed over 24 hours using an inoculum of 5 x 10(6) - 1 x 10(7) cfu/mL. Antibiotics were tested at the 1 x MIC and 4 x MIC concentrations. At MIC and/or 4 x MIC concentrations, the antibiotic combinations showed additive or synergistic activity against Acinetobacter strains and extended spectrum beta-lactamase producing Klebsiella pneumoniae. In Escherichia coli strains, synergy was seen when amikacin was combined with ertapenem, ciprofloxacin and levofloxacin; ertapenem in combination with fluoroquinolones demonstrated antagonism. In Pseudomonas aeruginosa strains, synergistic effect was exhibited by ertapenem plus amikacin and ertapenem plus fluoroquinolones. The antibiotic combinations showed antagonistic interaction in meth...
Mikrobiyoloji bülteni, 2007
The emergence of Staphylococcus aureus strains with intermediate resistance (VISA) and heterogen ... more The emergence of Staphylococcus aureus strains with intermediate resistance (VISA) and heterogen resistance (hVISA) to vancomycin leads to the occurence of severe therapeutic problems. The aim of this study was to investigate the vancomycin resistance in methicillin resistant S. aureus (MRSA) and coagulase-negative staphylococci (MRCoNS) isolated from clinical samples in Bacteriology Laboratory of Microbiology and Clinical Microbiology Department of Celal Bayar University Faculty of Medicine, Manisa (located in western Anatolia, Turkey). A total of 120 staphyloccoccal strains (92 MRSA and 28 MRCoNS) isolated from different clinical specimens (tracheal aspirate, blood, abscess, wound swabs, sputum, catheter tips, etc) between the period of June 2005 to December 2006 were included to the study. Vancomycin resistance were determined by agar screening method using brain hearth infusion agar plates containing 6 microg/mL vancomycin. Standard E-test and macro E-test methods were performed...
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Papers by Safak Ermertcan