Researcher: Ataç, Nazlı
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Ataç, Nazlı
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Publication Metadata only Efficacy of amikacin and meropenem on colistin-induced klebsiella pneumoniae persisters(Mary Ann Liebert, Inc, 2022) N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Vatansever, Cansel; Özer, Berna; Ataç, Nazlı; Güler, Orhan Ulaş; Kılıçoğlu, Bilge Kaan; Berkkan, Metehan; Başkurt, Defne; Sever, Egemen; Doğan, Özlem; Can, Füsun; Master Student; Researcher; Researcher; Undergraduate Student; Undergraduate Student; Undergraduate Student; Undergraduate Student; Undergraduate Student; Faculty Member; Graduate School of Health Sciences; N/A; N/A; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID); N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 103165Colistin-based antibiotic therapies have been recommended for the treatment of multidrug-resistant Klebsiella pneumoniae infections. During colistin treatment, persister cells that tolerate antibiotics may arise. Here we designed an in vitro study to assess the killing activity of colistin, meropenem, and amikacin on colistin-induced K. pneumoniae persisters in comparison with starvation-induced persisters. Colistin-induced persisters were generated under exposure to 10 x minimum inhibitory concentration dose of colistin, whereas starvation-induced persisters were produced by limitation of nutrients. In colistin-induced persisters, amikacin totally inhibited cell growth in 6 hours, whereas 98% of the cell population was inhibited by meropenem, and total eradication with meropenem was observed after 24 hours. Both antibiotics also inhibited metabolic activity >88%. The lack of killing effect under colistin exposure suggested to us that these cells could protect themselves from further colistin stress. There was no significant permeabilization change in the cellular membrane with all antibiotics. There was no killing effect on starvation-induced persister cells with the exposure to all antibiotics. In 6 hours, the metabolic activity of the persisters with meropenem and colistin increased 99% and 40%, respectively, whereas there was no increase with amikacin. The sustained inhibition with amikacin was an important finding for antipersister effect of amikacin. Amikacin had rapid and sustained antipersister activity on colistin-induced persister cells. During the colistin treatment of K. pneumoniae infection, the addition of amikacin to the regimen seems to be an effective approach to prevent a recurrence.Publication Metadata only Erythrocyte deformability responses to intermittent and continuous subhemolytic shear stress(IOS Press, 2014) Simmonds, Michael J.; Meiselman, Herbert J; Ataç, Nazlı; Başkurt, Oğuz Kerim; Yalçın, Özlem; Master Student; Faculty Member; Faculty Member; Graduate School of Sciences and Engineering; School of Medicine; School of Medicine; N/A; N/A; N/A; 218440Publication Metadata only The effects of hyperbaric oxygen therapy (HBOT) on blood viscosity and erythrocyte aggregation in diabetic patients(Wiley-Blackwell, 2014) Ertan, N. Z.; Sinan, M.; Mirasoğlu, B.; Toklu, A. S.; Yalçın, Özlem; Ataç, Nazlı; Faculty Member; Researcher; School of Medicine; School of Medicine; 218440; N/AThere are only a few studies about hyperbaric oxygen’s effect on hemorheological parameters and their results showed an increase in blood viscosity and RBC aggregation both in vivo and in vitro. Some many other studies showed abnormal hemorheological parameters in diabetics and so, this would suggest more complications after HBO therapy however; reality is not consistent with this suggestion. Therefore, in this study, the effects of hyperbaric oxygen therapy on blood viscosity and erythrocyte aggregation have been investigated. After the approval of local ethical committee, 11 diabetic ulcer patients aged between 42 and 82 were taken to our study. 100% oxygen was applied at 2.4 ATA for two hours in three cycles of 25 minutes of oxygen- 5 minutes air break. Treatments were carried on five days a week. Blood that was collected before the initial HBO therapy was accepted to be control. Samples were also collected after the initial therapy and twentieth one to be evaluated. Corrected whole blood viscosity was measured using a cone/plate viscometer with a hematocrit of 45%. RBC aggregation was measured using a Myrenne aggregometer in both autologous plasma and dextran70 solution. Our results showed that there were no significant changes in corrected blood viscosity between the samples collected before and after the first and twentieth HBO treatments. Also RBC aggregation in both autologous plasma and dextran70 solution after the first and twentieth HBO treatments were not significantly different than the control samples. These results were in contrast with the previous experimental studies. The reason of these contradictory results may be caused by experimental method and HBO application differences and/or different reactions of humans and animals. Still, this topic needs further studies to clear such an important effect.Publication Metadata only Impact of the ST101 clone on fatality among patients with colistin-resistant Klebsiella pneumoniae infection(Oxford University Press (OUP), 2018) Menekse, Şirin; Karahan, Salih Nafiz; Azap, Oztem Kurt; Timurkaynak, Funda; Yavuz, Serap Şimşek; Basaran, Seniha; Yörük, Fugen; Azap, Alpay; Koculu, Safiye; Benzonana, Nur; N/A; N/A; N/A; N/A; N/A; N/A; Department of Industrial Engineering; N/A; N/A; N/A; Can, Füsun; İspir, Pelin; Ataç, Nazlı; Albayrak, Özgür; Demir, Tuana; Karaaslan, Doruk Can; Gönen, Mehmet; Lack, Nathan Alan; Ergönül, Önder; Kapmaz, Mahir; Faculty Member; Master Student; Researcher; Researcher; Undergraduate Student; Undergraduate Student; Faculty Member; Faculty Member; Faculty Member; Doctor; Department of Industrial Engineering; Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID); School of Medicine; Graduate School of Health Sciences; N/A; N/A; School of Medicine; School of Medicine; College of Engineering; School of Medicine; School of Medicine; N/A; Koç University Hospital; 103165; N/A; N/A; N/A; N/A; N/A; 237468; 120842; 110398; N/AObjectives: We describe the molecular characteristics of colistin resistance and its impact on patient mortality. Methods: A prospective cohort study was performed in seven different Turkish hospitals. The genotype of each isolate was determined by MLST and repetitive extragenic palindromic PCR (rep-PCR). Alterations in mgrB were detected by sequencing. Upregulation of pmrCAB, phoQ and pmrK was quantified by RT-PCR. mcr-1 and the genes encoding OXA-48, NDM-1 and KPC were amplified by PCR. Results: A total of 115 patients diagnosed with colistin-resistant K. pneumoniae (ColR-Kp) infection were included. Patients were predominantly males (55%) with a median age of 63 (IQR 46-74) and the 30 day mortality rate was 61%. ST101 was the most common ST and accounted for 68 (59%) of the ColR-Kp. The 30 day mortality rate in patients with these isolates was 72%. In ST101, 94% (64/68) of the isolates had an altered mgrB gene, whereas the alteration occurred in 40% (19/47) of non-ST101 isolates. The OXA-48 and NDM-1 carbapenemases were found in 93 (81%) and 22 (19%) of the total 115 isolates, respectively. In multivariate analysis for the prediction of 30 day mortality, ST101 (OR 3.4, CI 1.46-8.15, P = 0.005) and ICU stay (OR 7.4, CI 2.23-29.61, P = 0.002) were found to be significantly associated covariates. Conclusions: Besides ICU stay, ST101 was found to be a significant independent predictor of patient mortality among those infected with ColR-Kp. A significant association was detected between ST101 and OXA-48. ST101 may become a global threat in the dissemination of colistin resistance and the increased morbidity and mortality of K. pneumoniae infection.Publication Metadata only Acute and long-term effects of hyperbaric oxygen therapy on hemorheological parameters in patients with various disorders(Ios Press, 2016) Sinan, Mukaddes; Ertan, Nesrin Zeynep; Mirasoglu, Bengusu; Toklu, Akin Savas; Basaran-Kucukgergin, Canan; Yalçın, Özlem; Başkurt, Oğuz Kerim; Ataç, Nazlı; Faculty Member; Faculty Member; Researcher; School of Medicine; School of Medicine; N/A; Koç University Hospital; 218440; N/A; N/AInhalation of 100% oxygen in a hyperbaric chamber has been accepted as a useful treatment for patients with various pathologies who suffer from hypoxia. The oxidative effects of hyperbaric oxygen (HBO) on RBCs have been investigated in animals but there is not enough data on hemorheological parameters in patients following HBO treatment (HBOT). In this study, we investigated the effect of HBO on hemorheological and haematological parameters during treatment. Red blood cell (RBC) deformability and aggregation, blood and plasma viscosity and superoxide dismutase activity were investigated in patients who underwent HBOT. Hematological parameters were determined by an electronic hematology analyzer. A Laser-assisted Optical Rotational Cell Analyzer (LORCA) was used to measure RBC deformability. RBC aggregation was measured for cells in autologous plasma and for cells resuspended in PBS containing Dextran70 (3%) by using a Myrenne Aggregometer. A Wells-Brookfield cone/plate rotational viscometer was used for viscosity measurements. According to our results, a significant decrement of the hematocrit and the RBC count was observed after the 20th session of HBOT compared to the baseline, but none of the hemorheological parameters changed significantly. Our results showed that HBOT did not cause any significant changes in hemorheological parameters, thereby not representing any problems for the patients.Publication Open Access Virulence determinants of colistin-resistant K. pneumoniae high-risk clones(Multidisciplinary Digital Publishing Institute (MDPI), 2021) Department of Industrial Engineering; Ergönül, Önder; Gönen, Mehmet; Can, Füsun; Doğan, Özlem; Vatansever, Cansel; Ataç, Nazlı; Albayrak, Özgür; Karahüseyinoğlu, Serçin; Şahin, Özgün Ekin; Kılıçoğlu, Bilge Kaan; Demiray, Atalay; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Undergraduate Student; Researcher; Faculty Member; Master Student; Department of Industrial Engineering; School of Medicine; Graduate School of Health Sciences; College of Engineering; 110398; 237468; 103165; 170418; N/A; N/A; N/A; 110772; N/A; N/A; N/AWe proposed the hypothesis that high-risk clones of colistin-resistant K. pneumoniae (ColR-Kp) possesses a high number of virulence factors and has enhanced survival capacity against the neutrophil activity. We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive ColR-Kp infections. The ST101 and ST395 ColR-Kp infections had higher 30-day mortality (58%, p = 0.005 and 75%, p = 0.003). The presence of yersiniabactin biosynthesis gene (ybtS) and ferric uptake operon associated gene (kfu) were significantly higher in ST101 (99%, p <= 0.001) and ST395 (94%, p < 0.012). Being in ICU (OR: 7.9; CI: 1.43-55.98; p = 0.024), kfu (OR:27.0; CI: 5.67-179.65; p < 0.001) and ST101 (OR: 17.2; CI: 2.45-350.40; p = 0.01) were found to be predictors of 30-day mortality. Even the neutrophil uptake of kfu+-ybtS+ ColR-Kp was significantly higher than kfu--ybtS- ColR-Kp (phagocytosis rate: 78% vs. 65%, p < 0.001), and the kfu+-ybtS+ ColR-Kp survived more than kfu--ybtS- ColR-Kp (median survival index: 7.90 vs. 4.22; p = 0.001). The kfu+-ybtS+ ColR-Kp stimulated excessive NET formation. Iron uptake systems in high-risk clones of colistin-resistant K. pneumoniae enhance the success of survival against the neutrophil phagocytic defense and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be a promising approach for the treatment of colistin-resistant high-risk clones of K. pneumoniae infections.Publication Open Access Comparison of crystal violet staining assay and XTT methods in the evaluation of biofilm formation in Candida parapsilosis candidemia isolates(Design Oriented Community (DOC), 2021) Can, Füsun; Doğan, Özlem; Ataç, Nazlı; Babuççu, Gizem; Faculty Member; Faculty Member; Researcher; School of Medicine; Graduate School of Health Sciences; 103165; 170418; N/A; N/AObjective: biofilm formation is one of the most important virulence factors of Candida species which leads to permanent infection foci by adhering to foreign materials and which are difficult to treat. Candida parapsilosis, which is one of the most common causes of candidemia in our country, is frequently isolated as a causative agent in catheterrelated infections. The most commonly used methods for evaluating the biofilm formation of Candida species are measuring cell viability with XTT (2,3-bis (2-methoxy-4-nitro-5- sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) and evaluating the total biofilm mass with crystal violet (CV). The aim of this study is to evaluate the biofilm formation ability of C. parapsilosis candidemia isolates by XTT and (CV) methods and compare these methods with each other. Materials and methods: C. parapsilosis isolates sent from various hospitals between 2015 and 2019 were included in the study retrospectively, and the species-level identification was performed using the matrix- assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) The biofilm formation of the isolates was compared based on the optical density (OD) values obtained by crystal violet and XTT methods. The biofilm formation of the isolates was evaluated by categorizing them into low, medium and high biofilm groups as ± 20% according to the median value of all strains. Results: totally, 79 C. parapsilosis candidemia isolates were included in this study and categorical compatibility between CV and XTT methods in low, medium and high biofilm groups was found as 69.6%, 60.6% and 73.9%, respectively. The OD values of the XTT method in the high biofilm group were found statistically significantly higher when compared with the values from the CV method. Conclusion: the compatibility of XTT and crystal violet methods in terms of biofilm measurement in C. parapsilosis isolates was considered acceptable, and no major variations were detected between the categories. According to these results, when evaluating the biofilm levels of C. parapsilosis isolates, high OD values obtained by the XTT method should be confirmed with the CV method.Publication Open Access The role of AcrAB-TolC Efflux pumps on quinolone resistance of E-coli ST131(Springer, 2018) Kurt-Azap, O.; Dolapcı, I.; Yeşilkaya, A.; Can, F.; N/A; Department of Industrial Engineering; Ergönül, Önder; Ataç, Nazlı; Gönen, Mehmet; Faculty Member; Researcher; Faculty Member; Department of Industrial Engineering; School of Medicine; College of Engineering; 110398; N/A; 237468Escherichia coli ST131 is a cause for global concern because of its high multidrug resistance and several virulence factors. In this study, the contribution of acrAB-TolC efflux system of E. coli ST131 to fluoroquinolone resistance was evaluated. A total of nonrepetitive 111 ciprofloxacin-resistant E. coli isolates were included in the study. Multilocus sequence typing was used for genotyping. Expressions of acrA, acrB, and TolC efflux pump genes were measured by RT-PCR. Mutations in marA, gyrA, parC, and aac(6)-lb-cr positivity were studied by Sanger sequencing. Sixty-four (57.7%) of the isolates were classified as ST131, and 52 (81.3%) of the ST131 isolates belonged to H30-Rx subclone. In ST131, CTX-M 15 positivity (73%) and aac(6)-lb-cr carriage (75%) were significantly higher than those in non-ST131 (12.8% and 51%, respectively) (P<0.05). The ampicillin-sulbactam (83%) resistance was higher, and gentamicin resistance (20%) was lower in ST131 than that in non-ST131 (64% and 55%, respectively) (P=0.001 and P=0.0002). Numbers of the isolates with MDR or XDR profiles did not differ in both groups. Multiple in-dels (up to 16) were recorded in all quinolone-resistant isolates. However, marA gene was more overexpressed in ST131 compared to that in non-ST131 (median 5.98 vs. 3.99; P=0.0007). Belonging to H30-Rx subclone, isolation site, ciprofloxacin MIC values did not correlate with efflux pump expressions. In conclusion, the marA regulatory gene of AcrAB-TolC efflux pump system has a significant impact on quinolone resistance and progression to MDR profile in ST131 clone. Efflux pump inhibitors might be alternative drugs for the treatment of infections caused by E. coli ST131 if used synergistically in combination with antibiotics.Publication Open Access Broad spectrum antibacterial photodynamic and photothermal therapy achieved with indocyanine green loaded SPIONs under near infrared irradiation(Royal Society of Chemistry (RSC), 2020) N/A; Department of Physics; Department of Chemistry; Bilici, Kübra; Ataç, Nazlı; Muti, Abdullah; Toker, Işınsu Baylam; Doğan, Özlem; Sennaroğlu, Alphan; Can, Füsun; Acar, Havva Funda Yağcı; Researcher; PhD Student; Faculty Member; Faculty Member; Faculty Member; Department of Physics; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; Graduate School of Health Sciences; School of Medicine; College of Sciences; N/A; N/A; N/A; N/A; 170418; 23851; 103165; 178902Antimicrobial photodynamic therapy (aPDT) and antimicrobial photothermal therapy (aPTT) are promising local and effective alternative therapies for antibiotic resistant bacterial infections and biofilms. A combination of nanoparticles and organic photosensitizers offers a great opportunity to combine PDT and PTT for effective eradication of both planktonic bacteria and their biofilms. In this work, photo-induced antibacterial activity of indocyanine green (ICG), 3-aminopropylsilane coated superparamagnetic iron oxide nanoparticles (APTMS@SPIONs) and ICG loaded APTMS@SPIONs was evaluated on planktonic cells and biofilms of Gram-negative (E. coli,K. pneumoniae,P. aeruginosa) and Gram-positive (S. epidermis) bacteria. A relatively low dose of ICG (25 mu g mL(-1)) and SPIONs (0.425 mu g mL(-1)nanoparticle) in combination with single, short (10 min) laser irradiation at 808 nm with a power of 1150 mW was used in this study. No dark toxicity of the agents or antibacterial effect of the laser irradiation was observed. The charge of the particles did not provide a significant difference in their penetration to Gram-negativeversusGram-positive bacterial strains or their biofilms. APTMS@SPION/laser treatment completely eliminatedP. aeruginosaand provided 7-log reduction in the colony forming unit (CFU) ofE. Coli, but was not effective on the other two bacteria. This is the first example for antibacterial phototoxicity of this nanoparticle. ICG/laser and ICG-APTMS@SPION/laser treatments provided complete killing of all planktonic cells. Successful eradication of all biofilms was achieved with ICG/laser (3.2-3.7 log reduction in CFUs) or ICG-APTMS@SPION/laser treatment (3.3-4.4 log reduction in CFUs). However, an exceptionally high, 6.5-log reduction as well as a dramatic difference between ICGversusICG/APTMS@SPION treatment was observed inK. pneumoniaebiofilms with ICG-APTMS@SPION/laser treatment. Investigation of the ROS production and increase in the local temperature of the biofilms that were subjected to phototherapy suggested a combination of aPTT and aPDT mechanisms for phototoxicity, exhibiting a synergistic effect when ICG-APTMS@SPION/laser was used. This approach opens an exciting and novel avenue in the fight against drug resistant infections by successfully utilizing the antimicrobial and antibiofilm activity of low dose FDA approved optically traceable ICG and relatively low cost clinically acceptable iron oxide nanoparticles to enable effective aPDT/aPTT combination, inducedviashort-duration laser irradiation at a near-infrared wavelength.Publication Open Access Effect of initial antifungal therapy on mortality among patients with bloodstream infections with different Candida species and resistance to antifungal agents: A multicentre observational study by the Turkish Fungal Infections Study Group(Elsevier, 2020) Yeşilkaya, A.; Menekşe, Güler Ö.; Karakoç, Ç.; Çınar, G.; Aydın, M.; Keske, Şahin, S.; Hacıseyitoğlu, D.; Yalçın, D.; Albayrak, Ö.; Can, F.; Doğan, Özlem; Kapmaz, Mahir; Tekin, Süda; Ataç, Nazlı; Albayrak, Özgür; Aksu, Ekin Deniz; Can, Füsun; Ergönül, Önder; Faculty Member; Researcher; Faculty Member; Faculty Member; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; 103165; 110398This study aimed to describe the effect of initial antifungal therapy on patient mortality and to detail the current distribution and resistance patterns of Candida spp. among patients with candidaemia. A prospective observational study was performed among consecutive patients with candidaemia from 10 Turkish medical centres between January 2015 and November 2018. The primary outcome was 10-day mortality. Species were identified using MALDI-TOF/MS. A total of 342 patients with candidaemia were included, of which 175 (51.2%) were male and 68 (19.9%) were aged <18 years. The most common species were Candida albicans (47.4%), Candida parapsilosis (26.6%), Candida tropicalis (9.6%) and Candida glabrata (7.6%). Among all Candida spp., the 10-day case fatality rate (CFR) was 32.2%. The CFR was highest in patients with C. albicans (57.3%) and lowest in patients with C. parapsilosis (21.8%). The resistance rate to fluconazole was 13% in C. parapsilosis, with no significant effect on mortality. No resistance to echinocandins was detected. In the multivariate analysis, being in the ICU [OR = 2.1 (95% CI 1.32–3.57); P = 0.002], renal failure [OR = 2.4 (1.41–3.97); P = 0.001], total parenteral nutrition [OR = 2 (1.22–3.47); P = 0.006], C. albicans infection [OR = 1.7 (1.06–2.82); P = 0.027] and echinocandin as primary agent [OR = 0.6 (0.36–0.99); P = 0.047] were significantly associated with mortality. Candidaemia is a deadly infection. Fluconazole resistance is emerging, although it was not significantly related to mortality. Using an echinocandin as the primary agent could be life-saving.