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Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are structurally related mycotoxins with cytotoxic and genotoxic properties. In the present study, we hypothesized that DNA damage induced by non-cytotoxic concentrations of single and combined mycotoxins could alter the phosphorylation of the checkpoint proteins Chk2 and FANCD2 (ELISA) in HepG2 and A549 cells. The cytotoxic potential (MTT test) of single and combined STC and 5-M-STC, the nature of their interaction (additivity, antagonism, or synergy) and DNA damage level (alkaline comet assay) in HepG2 and A549 cells were also investigated. All experiments were performed after 24 h of mycotoxin treatment. 5-M-STC was 10-folds more cytotoxic than STC to both HepG2 and A549 cells. Both mycotoxins are genotoxic to HepG2 and A549 cells by inducing both double and single DNA strand breaks that activate Chk2 (especially in HepG2 cells) but not the FANCD2 protein. STC exerted higher genotoxic potential than 5-M-STC in HepG2 and A549 cells when both toxins were applied individually at the same concentration. Dual combinations of non-cytotoxic mycotoxin concentrations showed additive to antagonizing cytotoxic and genotoxic effects. The absence and low activation of checkpoint proteins during prolonged exposure to non-cytotoxic concentrations of STC and 5-M-STC could support cell proliferation and carcinogenesis.
Sanja Dabelić; Domagoj Kifer; Daniela Jakšić; Nevenka Kopjar; Maja Klarić. Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins. Toxins 2021, 13, 464 .
AMA StyleSanja Dabelić, Domagoj Kifer, Daniela Jakšić, Nevenka Kopjar, Maja Klarić. Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins. Toxins. 2021; 13 (7):464.
Chicago/Turabian StyleSanja Dabelić; Domagoj Kifer; Daniela Jakšić; Nevenka Kopjar; Maja Klarić. 2021. "Sterigmatocystin, 5-Methoxysterigmatocistin, and Their Combinations are Cytotoxic and Genotoxic to A549 and HepG2 Cells and Provoke Phosphorylation of Chk2, but not FANCD2 Checkpoint Proteins." Toxins 13, no. 7: 464.
Interleukin (IL)-1α, IL-1β, IL-6, IL-8 and tumor necrosis factor (TNF)α contribute to inflammation in chronic obstructive pulmonary disease (COPD). We wanted to investigate their interrelations and association with disease severity, as well as to combine them with other inflammation-associated biomarkers and evaluate their predictive value and potential in identifying various patterns of systemic inflammation. One hundred and nine patients with stable COPD and 95 age- and sex-matched controls were enrolled in the study. Cytokines’ concentrations were determined in plasma samples by antibody-based multiplex immunosorbent assay kits. Investigated cytokines were increased in COPD patients but were not associated with disease or symptoms severity. IL-1β, IL-6 and TNFα showed the best discriminative values regarding ongoing inflammation in COPD. Inflammatory patterns were observed in COPD patients when cytokines, C-reactive protein (CRP), fibrinogen (Fbg), extracellular adenosine triphosphate (eATP), extracellular heat shock protein 70 (eHsp70) and clinical data were included in cluster analysis. IL-1β, eATP and eHsp70 combined correctly classified 91% of cases. Therefore, due to the heterogeneity of COPD, its assessment could be improved by combination of biomarkers. Models including IL-1β, eATP and eHsp70 might identify COPD patients, while IL-1β, IL-6 and TNFα combined with CRP, Fbg, eATP and eHsp70 might be informative regarding various COPD clinical subgroups.
Iva Hlapčić; Daniela Belamarić; Martina Bosnar; Domagoj Kifer; Andrea Vukić Dugac; Lada Rumora. Combination of Systemic Inflammatory Biomarkers in Assessment of Chronic Obstructive Pulmonary Disease: Diagnostic Performance and Identification of Networks and Clusters. Diagnostics 2020, 10, 1029 .
AMA StyleIva Hlapčić, Daniela Belamarić, Martina Bosnar, Domagoj Kifer, Andrea Vukić Dugac, Lada Rumora. Combination of Systemic Inflammatory Biomarkers in Assessment of Chronic Obstructive Pulmonary Disease: Diagnostic Performance and Identification of Networks and Clusters. Diagnostics. 2020; 10 (12):1029.
Chicago/Turabian StyleIva Hlapčić; Daniela Belamarić; Martina Bosnar; Domagoj Kifer; Andrea Vukić Dugac; Lada Rumora. 2020. "Combination of Systemic Inflammatory Biomarkers in Assessment of Chronic Obstructive Pulmonary Disease: Diagnostic Performance and Identification of Networks and Clusters." Diagnostics 10, no. 12: 1029.
Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are mycotoxins produced by common damp indoor Aspergilli series Versicolores. Since both STC and 5-M-STC were found in the dust of indoor occupational and living areas, their occupants may be exposed to these mycotoxins, primarily by inhalation. Thus, STC and 5-M-STC were intratracheally instilled in male Wistar rats using doses (0.3 mg STC/kg of lung weight (l.w.); 3.6 mg 5-M-STC/kg l.w.; toxin combination 0.3 + 3.6 mg/kg l.w.) that corresponded to concentrations detected in the dust of damp indoor areas in order to explore cytotoxicity, vascular permeability, immunomodulation and genotoxicity. Single mycotoxins and their combinations insignificantly altered lactate-dehydrogenase activity, albumin, interleukin-6, tumor necrosis factor-α and chemokine macrophage inflammatory protein-1α concentrations, as measured by ELISA in bronchioalveolar lavage fluid upon 24 h of treatment. In an alkaline comet assay, both mycotoxins provoked a similar intensity of DNA damage in rat lungs, while in a neutral comet assay, only 5-M-STC evoked significant DNA damage. Hence, naturally occurring concentrations of individual STC may induce DNA damage in rat lungs, in which single DNA strand breaks prevail, while 5-M-STC was more responsible for double-strand breaks. In both versions of the comet assay treatment with STC + 5-M-STC, less DNA damage intensity occurred compared to single mycotoxin treatment, suggesting an antagonistic genotoxic action.
Daniela Jakšić; Ida Ćurtović; Domagoj Kifer; Dubravka Rašić; Nevenka Kopjar; Vedran Micek; Maja Peraica; Maja Šegvić Klarić. Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs. Toxins 2020, 12, 734 .
AMA StyleDaniela Jakšić, Ida Ćurtović, Domagoj Kifer, Dubravka Rašić, Nevenka Kopjar, Vedran Micek, Maja Peraica, Maja Šegvić Klarić. Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs. Toxins. 2020; 12 (11):734.
Chicago/Turabian StyleDaniela Jakšić; Ida Ćurtović; Domagoj Kifer; Dubravka Rašić; Nevenka Kopjar; Vedran Micek; Maja Peraica; Maja Šegvić Klarić. 2020. "Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs." Toxins 12, no. 11: 734.
Mycotoxin-producing Aspergilli (Circumdati, Flavi, and Nigri), usually associated with contaminated food, may also cause respiratory disorders and are insufficiently studied in water-damaged indoor environments. Airborne (N = 71) and dust borne (N = 76) Aspergilli collected at post-flood and control locations in Croatia resulted in eleven different species based on their calmodulin marker: A. ochraceus, A. ostianus, A. pallidofulvus, A. sclerotiorum, and A. westerdijkiae (Circumdati); A. flavus (Flavi); and A. tubingensis, A. welwitschiae, A. niger, A. piperis, and A. uvarum (Nigri). Most of the airborne (73%) and dust borne (54%) isolates were found at post-flood locations, and the highest concentrations measured in indoor air (5720 colony-forming units (CFU)/m3) and dust (2.5 × 105 CFU/g) were up to twenty times higher than in the control locations. A. flavus dominated among airborne isolates (25%) at the unrepaired locations, while 56% of the dust borne Aspergilli were identified as A. tubingensis and A. welwitschiae. The ability of identified isolates to produce mycotoxins aflatoxin B1 (AFB1), fumonisin B2 (FB2), and ochratoxin A were assessed by LC-MS analysis. All ochratoxin A (OTA)-producing Circumdati belonged to A. westerdijkiae (13.7 ± 15.81 µg/mL); in the section, FlaviA. flavus produced AFB1 (2.51 ± 5.31 µg/mL), while A. welwitschiae and A. niger (section Nigri) produced FB2 (6.76 ± 13.51 µg/mL and 11.24 ± 18.30 µg/mL, respectively). Water damage dominantly supported the occurrence of aflatoxigenic A. flavus in indoor environments. Yet unresolved, the causal relationship of exposure to indoor Aspergilli and adverse health effects may support the significance of this research.
Daniela Jakšić; Miranda Sertić; Sándor Kocsubé; Ivana Kovačević; Domagoj Kifer; Ana Mornar; Biljana Nigović; Maja Šegvić Klarić. Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment. Journal of Fungi 2020, 6, 282 .
AMA StyleDaniela Jakšić, Miranda Sertić, Sándor Kocsubé, Ivana Kovačević, Domagoj Kifer, Ana Mornar, Biljana Nigović, Maja Šegvić Klarić. Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment. Journal of Fungi. 2020; 6 (4):282.
Chicago/Turabian StyleDaniela Jakšić; Miranda Sertić; Sándor Kocsubé; Ivana Kovačević; Domagoj Kifer; Ana Mornar; Biljana Nigović; Maja Šegvić Klarić. 2020. "Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment." Journal of Fungi 6, no. 4: 282.
Multiple sclerosis (MS) is an inflammatory autoimmune disorder affecting the central nervous system (CNS), with unresolved aetiology. Previous studies have implicated N-glycosylation, a highly regulated enzymatic attachment of complex sugars to targeted proteins, in MS pathogenesis. We investigated individual variation in N-glycosylation of the total plasma proteome and of IgG in MS. Both plasma protein and IgG N-glycans were chromatographically profiled and quantified in 83 MS cases and 88 age- and sex-matched controls. Comparing levels of glycosylation features between MS cases and controls revealed that core fucosylation (p = 6.96 × 10−3) and abundance of high-mannose structures (p = 1.48 × 10−2) were the most prominently altered IgG glycosylation traits. Significant changes in plasma protein N-glycome composition were observed for antennary fucosylated, tri- and tetrasialylated, tri- and tetragalactosylated, high-branched N-glycans (p-value range 1.66 × 10−2–4.28 × 10−2). Classification performance of N-glycans was examined by ROC curve analysis, resulting in an AUC of 0.852 for the total plasma N-glycome and 0.798 for IgG N-glycome prediction models. Our results indicate that multiple aspects of protein glycosylation are altered in MS, showing increased proinflammatory potential. N-glycan alterations showed substantial value in classification of the disease status, nonetheless, additional studies are warranted to explore their exact role in MS development and utility as biomarkers.
Ana Cvetko; Domagoj Kifer; Olga Gornik; Lucija Klarić; Elizabeth Visser; Gordan Lauc; James F. Wilson; Tamara Štambuk. Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential. Biomedicines 2020, 8, 410 .
AMA StyleAna Cvetko, Domagoj Kifer, Olga Gornik, Lucija Klarić, Elizabeth Visser, Gordan Lauc, James F. Wilson, Tamara Štambuk. Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential. Biomedicines. 2020; 8 (10):410.
Chicago/Turabian StyleAna Cvetko; Domagoj Kifer; Olga Gornik; Lucija Klarić; Elizabeth Visser; Gordan Lauc; James F. Wilson; Tamara Štambuk. 2020. "Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential." Biomedicines 8, no. 10: 410.
BackgroundMost respiratory viruses show pronounced seasonality, but for SARS-CoV-2 this still needs to be documented.MethodsWe examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application.FindingsMeta-analysis of the mortality risk in seven European hospitals estimated odds ratios per one day increase in the admission date to be 0.981 (0.973-0.988, pInterpretationSeverity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.
Domagoj Kifer; Dario Bugada; Judit Villar-Garcia; Ivan Gudelj; Cristina Menni; Carole Helene Sudre; Frano Vučković; Ivo Ugrina; Luca F Lorini; Margarita Posso; Silvia Bettinelli; Nicola Ughi; Alessandro Maloberti; Oscar Epis; Cristina Giannattasio; Claudio Rossetti; Livije Kalogjera; Jasminka Peršec; Luke Ollivere; Benjamin J Ollivere; Huadong Yan; Ting Cai; Guruprasad P. Aithal; Claire J Steves; Anu Kantele; Mikael Kajova; Olli Vapalahti; Antti Sajantila; Rafal Wojtowicz; Waldemar Wierzba; Zbigniew Krol; Artur Zaczynski; Katarzyna Zycinska; Marek Postula; Ivica Lukšić; Rok Čivljak; Alemka Markotić; Johannes Brachmann; Andreas Markl; Christian Mahnkopf; Benjamin Murray; Sebastien Ourselin; Ana M. Valdes; Juan P Horcajada; Xavier Castells; Julio Pascual; Massimo Allegri; Dragan Primorac; Timothy Spector; Clara Barrios; Gordan Lauc. Effects of environmental factors on severity and mortality of COVID-19. 2020, 1 .
AMA StyleDomagoj Kifer, Dario Bugada, Judit Villar-Garcia, Ivan Gudelj, Cristina Menni, Carole Helene Sudre, Frano Vučković, Ivo Ugrina, Luca F Lorini, Margarita Posso, Silvia Bettinelli, Nicola Ughi, Alessandro Maloberti, Oscar Epis, Cristina Giannattasio, Claudio Rossetti, Livije Kalogjera, Jasminka Peršec, Luke Ollivere, Benjamin J Ollivere, Huadong Yan, Ting Cai, Guruprasad P. Aithal, Claire J Steves, Anu Kantele, Mikael Kajova, Olli Vapalahti, Antti Sajantila, Rafal Wojtowicz, Waldemar Wierzba, Zbigniew Krol, Artur Zaczynski, Katarzyna Zycinska, Marek Postula, Ivica Lukšić, Rok Čivljak, Alemka Markotić, Johannes Brachmann, Andreas Markl, Christian Mahnkopf, Benjamin Murray, Sebastien Ourselin, Ana M. Valdes, Juan P Horcajada, Xavier Castells, Julio Pascual, Massimo Allegri, Dragan Primorac, Timothy Spector, Clara Barrios, Gordan Lauc. Effects of environmental factors on severity and mortality of COVID-19. . 2020; ():1.
Chicago/Turabian StyleDomagoj Kifer; Dario Bugada; Judit Villar-Garcia; Ivan Gudelj; Cristina Menni; Carole Helene Sudre; Frano Vučković; Ivo Ugrina; Luca F Lorini; Margarita Posso; Silvia Bettinelli; Nicola Ughi; Alessandro Maloberti; Oscar Epis; Cristina Giannattasio; Claudio Rossetti; Livije Kalogjera; Jasminka Peršec; Luke Ollivere; Benjamin J Ollivere; Huadong Yan; Ting Cai; Guruprasad P. Aithal; Claire J Steves; Anu Kantele; Mikael Kajova; Olli Vapalahti; Antti Sajantila; Rafal Wojtowicz; Waldemar Wierzba; Zbigniew Krol; Artur Zaczynski; Katarzyna Zycinska; Marek Postula; Ivica Lukšić; Rok Čivljak; Alemka Markotić; Johannes Brachmann; Andreas Markl; Christian Mahnkopf; Benjamin Murray; Sebastien Ourselin; Ana M. Valdes; Juan P Horcajada; Xavier Castells; Julio Pascual; Massimo Allegri; Dragan Primorac; Timothy Spector; Clara Barrios; Gordan Lauc. 2020. "Effects of environmental factors on severity and mortality of COVID-19." , no. : 1.
Glycan age is a recently developed biomarker based on glycans attached to immunoglobulin G (IgG). In large population cohorts glycan age associates well with lifestyle and disease-risk biomarkers, while some studies suggested that change in glycans precede development of several age-associated diseases. In this study we evaluated effects of estrogen on the glycan age. Gonadal hormones were suppressed in 36 healthy young women by gonadotropin releasing hormone agonist therapy for 6 months. In 15 of them estradiol was supplemented, while 21 received placebo resulting in very low estrogen levels during intervention. IgG was isolated from plasma samples before intervention, after 6 months of intervention and after subsequent 4-month recovery. In the placebo group the removal of gonadal hormones resulted in median increase of glycan age for 9.1 years (IQR 6.8 – 11.5 years, p = 3.73×10−8), which was completely prevented by transdermal estradiol supplementation. After the recovery period glycan age returned to baseline values also in the placebo group. These results suggest that IgG glycans and consequently also the glycan age are under strong influence of gonadal hormones and that hormone replacement therapy can prevent the increase of glycan age that occurs in the perimenopausal period.
Julija Jurić; Wendy M. Kohrt; Domagoj Kifer; Marija Pezer; Peter A. Nigrovic; Gordan Lauc. Effects of estradiol on biological age measured using the glycan age index. 2020, 1 .
AMA StyleJulija Jurić, Wendy M. Kohrt, Domagoj Kifer, Marija Pezer, Peter A. Nigrovic, Gordan Lauc. Effects of estradiol on biological age measured using the glycan age index. . 2020; ():1.
Chicago/Turabian StyleJulija Jurić; Wendy M. Kohrt; Domagoj Kifer; Marija Pezer; Peter A. Nigrovic; Gordan Lauc. 2020. "Effects of estradiol on biological age measured using the glycan age index." , no. : 1.
Background Obesity is a major global health problem, and is associated with increased cardiometabolic morbidity and mortality. Protein glycosylation is a frequent postranslational modification, highly responsive to numerous pathophysiological conditions and ageing. The prospect of biological age reduction, by reverting glycosylation changes through metabolic intervention, opens many possibilities. We have investigated whether weight loss interventions affect inflammation- and ageing-associated IgG glycosylation changes, in a longitudinal cohort of bariatric surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal twins cohort. Methods IgG N-glycans were chromatographically profiled in 37 obese patients, subjected to low-calorie diet, followed by bariatric surgery, across multiple timepoints. Similarly, plasma-derived IgG N-glycan traits were longitudinally monitored in 1,680 participants from the TwinsUK cohort. Results Low-calorie diet induced a marked decrease in the levels of IgG N-glycans with bisecting GlcNAc, whose higher levels are usually associated with ageing and inflammatory conditions. Bariatric surgery resulted in extensive alterations of the IgG glycome that accompanied progressive weight loss during one-year follow-up. We observed a significant increase in digalactosylated and sialylated glycans, and a substantial decrease in agalactosylated and core fucosylated IgG glycans. In general, this IgG glycan profile is associated with a younger biological age and reflects an enhanced anti-inflammatory IgG potential. Loss of BMI over a 20 year period in the TwinsUK cohort validated a weight loss-associated agalactosylation decrease and an increase in digalactosylation. Conclusions Altogether, these findings highlight that weight loss substantially affects IgG N-glycosylation, resulting in reduced biological and immune age. GRAPHICAL ABSTRACT HIGHLIGHTS Obesity is associated to inflammation-related agalactosylated and bisected IgG glycoforms IgG galactosylation and sialylation increase after bariatric surgery-induced weight loss Progressive decrease of BMI is associated to increased IgG galactosylation, implying a reduction of biological age
Valentina L Greto; Ana Cvetko; Tamara Štambuk; Niall J Dempster; Domagoj Kifer; Helena Deriš; Ana Cindrić; Frano Vučković; Mario Falchi; Richard S Gillies; Jeremy W Tomlinson; Olga Gornik; Bruno Sgromo; Tim D Spector; Cristina Menni; Alessandra Geremia; Carolina V Arancibia-Cárcamo; Gordan Lauc. Extensive weight loss can reduce immune age by altering IgG N-glycosylation. 2020, 1 .
AMA StyleValentina L Greto, Ana Cvetko, Tamara Štambuk, Niall J Dempster, Domagoj Kifer, Helena Deriš, Ana Cindrić, Frano Vučković, Mario Falchi, Richard S Gillies, Jeremy W Tomlinson, Olga Gornik, Bruno Sgromo, Tim D Spector, Cristina Menni, Alessandra Geremia, Carolina V Arancibia-Cárcamo, Gordan Lauc. Extensive weight loss can reduce immune age by altering IgG N-glycosylation. . 2020; ():1.
Chicago/Turabian StyleValentina L Greto; Ana Cvetko; Tamara Štambuk; Niall J Dempster; Domagoj Kifer; Helena Deriš; Ana Cindrić; Frano Vučković; Mario Falchi; Richard S Gillies; Jeremy W Tomlinson; Olga Gornik; Bruno Sgromo; Tim D Spector; Cristina Menni; Alessandra Geremia; Carolina V Arancibia-Cárcamo; Gordan Lauc. 2020. "Extensive weight loss can reduce immune age by altering IgG N-glycosylation." , no. : 1.
Correspondence between evolution and development has been discussed for more than two centuries1. Recent work reveals that phylogeny-ontogeny correlations are indeed present in developmental transcriptomes of eukaryotic clades with complex multicellularity2–10. Nevertheless, it has been largely ignored that the pervasive presence of phylogeny-ontogeny correlations is a hallmark of development in eukaryotes6, 10–12. This perspective opens a possibility to look for similar parallelisms in biological settings where developmental logic and multicellular complexity are more obscure13–16. For instance, it has been increasingly recognized that multicellular behaviour underlies biofilm formation in bacteria13, 14, 17–19. However, it remains unclear whether bacterial biofilm growth shares some basic principles with development in complex eukaryotes14–16, 18, 20. Here we show that the ontogeny of growing Bacillus subtilis biofilms recapitulates phylogeny at the expression level. Using time-resolved transcriptome and proteome profiles, we found that biofilm ontogeny correlates with the evolutionary measures, in a way that evolutionary younger and more diverged genes were increasingly expressed towards later timepoints of biofilm growth. Molecular and morphological signatures also revealed that biofilm growth is highly regulated and organized into discrete ontogenetic stages, analogous to those of eukaryotic embryos11, 21. Together, this suggests that biofilm formation in Bacillus is a bona fide developmental process comparable to organismal development in animals, plants and fungi. Given that most cells on Earth reside in the form of biofilms22and that biofilms represent the oldest known fossils23, we anticipate that the widely-adopted vision of the first life as a single-cell and free-living organism needs rethinking.
Momir Futo; Luka Opašić; Sara Koska; Nina Čorak; Tin Široki; Vaishnavi Ravikumar; Annika Thorsell; Domagoj Kifer; Mirjana Domazet-Lošo; Kristian Vlahoviček; Ivan Mijaković; Tomislav Domazet-Lošo. Embryo-like features in developingBacillus subtilisbiofilms. 2020, 1 .
AMA StyleMomir Futo, Luka Opašić, Sara Koska, Nina Čorak, Tin Široki, Vaishnavi Ravikumar, Annika Thorsell, Domagoj Kifer, Mirjana Domazet-Lošo, Kristian Vlahoviček, Ivan Mijaković, Tomislav Domazet-Lošo. Embryo-like features in developingBacillus subtilisbiofilms. . 2020; ():1.
Chicago/Turabian StyleMomir Futo; Luka Opašić; Sara Koska; Nina Čorak; Tin Široki; Vaishnavi Ravikumar; Annika Thorsell; Domagoj Kifer; Mirjana Domazet-Lošo; Kristian Vlahoviček; Ivan Mijaković; Tomislav Domazet-Lošo. 2020. "Embryo-like features in developingBacillus subtilisbiofilms." , no. : 1.
In the past decades, many studies have examined the nature of the interaction between mycotoxins in biological models classifying interaction effects as antagonisms, additive effects, or synergisms based on a comparison of the observed effect with the expected effect of combination. Among several described mathematical models, the arithmetic definition of additivity and factorial analysis of variance were the most commonly used in mycotoxicology. These models are incorrectly based on the assumption that mycotoxin dose-effect curves are linear. More appropriate mathematical models for assessing mycotoxin interactions include Bliss independence, Loewe’s additivity law, combination index, and isobologram analysis, Chou-Talalays median-effect approach, response surface, code for the identification of synergism numerically efficient (CISNE) and MixLow method. However, it seems that neither model is ideal. This review discusses the advantages and disadvantages of these mathematical models.
Domagoj Kifer; Daniela Jakšić; Maja Šegvić Klarić. Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate? Toxins 2020, 12, 153 .
AMA StyleDomagoj Kifer, Daniela Jakšić, Maja Šegvić Klarić. Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate? Toxins. 2020; 12 (3):153.
Chicago/Turabian StyleDomagoj Kifer; Daniela Jakšić; Maja Šegvić Klarić. 2020. "Assessing the Effect of Mycotoxin Combinations: Which Mathematical Model Is (the Most) Appropriate?" Toxins 12, no. 3: 153.
Exercise is known to improve many aspects of human health, including modulation of the immune system and inflammatory status. It is generally understood that exercise reduces inflammation, but there are missing links in terms of understanding the mechanisms as well as the differences between exercise modalities. N-glycosylation of immunoglobulin G (IgG) and total plasma proteins was previously shown to reflect changes in inflammatory pathways, which could provide valuable information to further clarify exercise effects. In order to further expand the understanding of the relationship between physical activity and inflammation, we examined the effect of intense exercise, in the form of repeated sprint training (RST), on IgG and total plasma proteins N-glycosylation in combination with traditionally used inflammation markers: C-reactive protein (CRP), interleukin 6 (IL-6), and leukocyte count. Twenty-nine male physical education students were separated into treatment (RST, N = 15) and control (N = 14) groups. The RST group completed a 6-week exercise protocol while the control group was instructed to refrain from organized physical activity for the duration of the study. Three blood samples were taken at different time points: prior to start of the training program, the final week of the exercise intervention (EXC), and at the end of the 4-week recovery period (REC). Following the end of the recovery period IgG N-glycosylation profiles showed anti-inflammatory changes in RST group compared to the control group, which manifested as a decrease in agalactosylated (p = 0.0473) and an increase in digalactosylated (p = 0.0473), and monosialylated (p = 0.0339) N-glycans. Plasma protein N-glycans didn’t change significantly, while traditional inflammatory markers also didn’t show significant change in inflammatory status. Observed results demonstrate the potential of intense physical exercise to reduce levels of systemic basal inflammation as well as the potential for IgG N-glycosylation to serve as a sensitive longitudinal systemic inflammation marker.
Marko Tijardović; Domagoj Marijančević; Daniel Bok; Domagoj Kifer; Gordan Lauc; Olga Gornik; Toma Keser. Intense Physical Exercise Induces an Anti-inflammatory Change in IgG N-Glycosylation Profile. Frontiers in Physiology 2019, 10, 1 .
AMA StyleMarko Tijardović, Domagoj Marijančević, Daniel Bok, Domagoj Kifer, Gordan Lauc, Olga Gornik, Toma Keser. Intense Physical Exercise Induces an Anti-inflammatory Change in IgG N-Glycosylation Profile. Frontiers in Physiology. 2019; 10 ():1.
Chicago/Turabian StyleMarko Tijardović; Domagoj Marijančević; Daniel Bok; Domagoj Kifer; Gordan Lauc; Olga Gornik; Toma Keser. 2019. "Intense Physical Exercise Induces an Anti-inflammatory Change in IgG N-Glycosylation Profile." Frontiers in Physiology 10, no. : 1.
Background: Obesity-related hypertension is a common disorder, and attempts to combat the underlying obesity are often unsuccessful. We previously revealed that mice globally deficient in the inhibitory immunoglobulin G (IgG) receptor FcγRIIB are protected from obesity-induced hypertension. However, how FcγRIIB participates is unknown. Studies were designed to determine if alterations in IgG contribute to the pathogenesis of obesity-induced hypertension. Methods: Involvement of IgG was studied using IgG μ heavy chain–null mice deficient in mature B cells and by IgG transfer. Participation of FcγRIIB was interrogated in mice with global or endothelial cell–specific deletion of the receptor. Obesity was induced by high-fat diet (HFD), and blood pressure (BP) was measured by radiotelemetry or tail cuff. The relative sialylation of the Fc glycan on mouse IgG, which influences IgG activation of Fc receptors, was evaluated by Sambucus nigra lectin blotting. Effects of IgG on endothelial NO synthase were assessed in human aortic endothelial cells. IgG Fc glycan sialylation was interrogated in 3442 human participants by mass spectrometry, and the relationship between sialylation and BP was evaluated. Effects of normalizing IgG sialylation were determined in HFD-fed mice administered the sialic acid precursor N-acetyl-D-mannosamine (ManNAc). Results: Mice deficient in B cells were protected from obesity-induced hypertension. Compared with IgG from control chow–fed mice, IgG from HFD-fed mice was hyposialylated, and it raised BP when transferred to recipients lacking IgG; the hypertensive response was absent if recipients were FcγRIIB-deficient. Neuraminidase-treated IgG lacking the Fc glycan terminal sialic acid also raised BP. In cultured endothelial cells, via FcγRIIB, IgG from HFD-fed mice and neuraminidase-treated IgG inhibited vascular endothelial growth factor activation of endothelial NO synthase by altering endothelial NO synthase phosphorylation. In humans, obesity was associated with lower IgG sialylation, and systolic BP was inversely related to IgG sialylation. Mice deficient in FcγRIIB in endothelium were protected from obesity-induced hypertension. Furthermore, in HFD-fed mice, ManNAc normalized IgG sialylation and prevented obesity-induced hypertension. Conclusions: Hyposialylated IgG and FcγRIIB in endothelium are critically involved in obesity-induced hypertension in mice, and supportive evidence was obtained in humans. Interventions targeting these mechanisms, such as ManNAc supplementation, may provide novel means to break the link between obesity and hypertension.
Jun Peng; Wanpen Vongpatanasin; Anastasia Sacharidou; Domagoj Kifer; Ivan S. Yuhanna; Subhashis Banerjee; Keiji Tanigaki; Ozren Polasek; Haiyan Chu; Nathan C. Sundgren; Anand Rohatgi; Ken L. Chambliss; Gordan Lauc; Chieko Mineo; Philip W. Shaul. Supplementation With the Sialic Acid Precursor N-Acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension. Circulation 2019, 140, 2005 -2018.
AMA StyleJun Peng, Wanpen Vongpatanasin, Anastasia Sacharidou, Domagoj Kifer, Ivan S. Yuhanna, Subhashis Banerjee, Keiji Tanigaki, Ozren Polasek, Haiyan Chu, Nathan C. Sundgren, Anand Rohatgi, Ken L. Chambliss, Gordan Lauc, Chieko Mineo, Philip W. Shaul. Supplementation With the Sialic Acid Precursor N-Acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension. Circulation. 2019; 140 (24):2005-2018.
Chicago/Turabian StyleJun Peng; Wanpen Vongpatanasin; Anastasia Sacharidou; Domagoj Kifer; Ivan S. Yuhanna; Subhashis Banerjee; Keiji Tanigaki; Ozren Polasek; Haiyan Chu; Nathan C. Sundgren; Anand Rohatgi; Ken L. Chambliss; Gordan Lauc; Chieko Mineo; Philip W. Shaul. 2019. "Supplementation With the Sialic Acid Precursor N-Acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension." Circulation 140, no. 24: 2005-2018.
Antibiotics reserve (ARs) are given as a last line of treatment when other antibiotics are no longer effective. Rising threat of antimicrobial resistance makes growing use of ARs a real problem to patient safety. A single centre interventional cohort study was conducted in order to measure impact on clinical outcomes of A-team programme with limited human resources in a short period. A-team programme started on 01. September 2017. In 3 months preintervention and 3 months intervention period, from 3038 and 3156 hospitalized adult patients, 249 (59% of them were male, median age = 69 years) and 96 (51% of them were male, median age = 70 years) received parenteral ARs. Total duration of hospitalization of patients on AR was reduced from 28 to 17 days of hospitalization on 100 patient-days (OR = 1.92; 95% CI 1.83–2.01; p < 0.001) with no statistical significant difference in rehospitalisation due to infection of patients that were treated with ARs within 2 months after discharge. Despite short period of time and limited human resources, A-team restrictive interventions rationalised parenteral AR use and led to positive impact on clinical outcomes. These results could help our and other A-teams in similar situation in continuing with the programme to bring more evidence.
Darija Kuruc Poje; Vesna Mađarić; Vlatka Janeš Poje; Domagoj Kifer; Philip Howard; Srećko Marušić. Antimicrobial stewardship effectiveness on rationalizing the use of last line of antibiotics in a short period with limited human resources: a single centre cohort study. BMC Research Notes 2019, 12, 1 -6.
AMA StyleDarija Kuruc Poje, Vesna Mađarić, Vlatka Janeš Poje, Domagoj Kifer, Philip Howard, Srećko Marušić. Antimicrobial stewardship effectiveness on rationalizing the use of last line of antibiotics in a short period with limited human resources: a single centre cohort study. BMC Research Notes. 2019; 12 (1):1-6.
Chicago/Turabian StyleDarija Kuruc Poje; Vesna Mađarić; Vlatka Janeš Poje; Domagoj Kifer; Philip Howard; Srećko Marušić. 2019. "Antimicrobial stewardship effectiveness on rationalizing the use of last line of antibiotics in a short period with limited human resources: a single centre cohort study." BMC Research Notes 12, no. 1: 1-6.
Background Juvenile idiopathic arthritis (JIA) is the most frequent childhood systemic disease affiliated with uveitis, where uveitis occurs in 10-13% of the patients, frequently causing long lasting consequences when unrecognized, untimely or incorrectly treated. Objectives To explore correlations between age, gender, ANA, RF titer in patients with JIA, occurrence of ocular manifestations and its complications. To examine similarities and differences between patients with different subtypes of JIA and uveitis. Methods The retrospective study included 31 children treated for JIA and uveitis in the period 2009-2017 at the Department of Paediatrics, UHC Zagreb. The SUN working group classification and grading system were used to evaluate ocular manifestations. Data analysis was executed using R programming language. Results We followed 31 patients (81% female) suffering from JIA with ocular manifestations. Median age at JIA onset in girls was 2.5 (1-14) years and in boys 8.6 (1-14.5) years, while girls had median age 4.25 (1-14) years at first ocular manifestation and boys 8.25 (4 -13.5) years. All patients were RF negative. 61% of patients was ANA positive, out of which 88% had onset of JIA before the age of 6 (all girls). Complete remission of uveitis was achieved in two patients treated with topical corticosteroids, with non-steroid anti-inflammatory medication and methotrexate used in one of the patients. Inactive uveitis was most frequently achieved with a combined therapy which included biologics. A patient suffering from uveitis and JIA was found to be significantly more likely to suffer from oligoarthritic subtype (64.5%, CI 45.4-80.8%, p<0.001). We determined that a positive ANA titer occurred statistically significantly more frequent in females (OR inf., CI 3.18-inf., p=0.001). No significant statistical difference in ANA titer was found between groups of patients who were diagnosed with rheumatologic or ocular disease before and after the age of 6 (OR 1.85, CI 0.12-29.57, p=0.6111) nor between different subtypes of JIA. There was no difference in time passed between the occurrence of rheumatologic and ocular manifestations (median difference =1.75 years, W=131, p=0.2597), nor between ANA titer (OR 0.57, CI 0.09-3.12, p=0.4775) between groups with and without ocular complications. Patients who first presented with ocular manifestations did not have a greater likelihood to develop ocular complications (OR 5.59, CI 0.51-299.98, p=0.175). Conclusion A group of female patients suffering from RF negative subtypes of JIA and uveitis, with onset occurring before the age of 6 and positive ANA was prominent. These patients were traditionally classified as different subtypes of JIA, but together, they are best described as “early onset ANA positive JIA”, concurring the need for reclassification of JIA. Limited by a small number of patients, this was partly confirmed with significant statistical findings, a recurrent positive ANA titer in females with JIA and uveitis and a more frequent occurrence of uveitis in oligoarthritis. The occurrence of ocular complications was not dependent upon ANA titer, nor upon the time difference between rheumatic and ocular symptoms or their order of appearance. Reference [1] Martini A., Ravelli A., Avcin T. el al. Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatric Rheumatology International Trials Organization International Consensus. J Rheumatol. 2018;Oct1. Disclosure of Interests None declared
Nastasia Kifer; Mihovil Hrgovic; Mario Sestan; Sanja Peric; Domagoj Kifer; Marijan Frkovic; Kristina Potocki; Nenad Vukojevic; Marija Jelusic. AB0995 EXPLORING UVEITIS IN EARLY ONSET ANA POSITIVE JIA. Abstracts Accepted for Publication 2019, 78, 1963 -1964.
AMA StyleNastasia Kifer, Mihovil Hrgovic, Mario Sestan, Sanja Peric, Domagoj Kifer, Marijan Frkovic, Kristina Potocki, Nenad Vukojevic, Marija Jelusic. AB0995 EXPLORING UVEITIS IN EARLY ONSET ANA POSITIVE JIA. Abstracts Accepted for Publication. 2019; 78 ():1963-1964.
Chicago/Turabian StyleNastasia Kifer; Mihovil Hrgovic; Mario Sestan; Sanja Peric; Domagoj Kifer; Marijan Frkovic; Kristina Potocki; Nenad Vukojevic; Marija Jelusic. 2019. "AB0995 EXPLORING UVEITIS IN EARLY ONSET ANA POSITIVE JIA." Abstracts Accepted for Publication 78, no. : 1963-1964.
The study aimed to check whether ochratoxin A (OTA) and citrinin (CIT) increase DNA damage in the kidney and liver of male Wistar rats (alkaline comet assay), clarify the oxidative nature of DNA damage (hOGG1-modified comet assay), and verify whether resveratrol (RSV) could ameliorate OTA+CIT-induced genotoxicity. Rats were treated orally with OTA (0.125 and 0.250 mg/kg bodyweight (bw)) and CIT (2 mg/kg bw), OTA+CIT combinations and OTA+CIT+RSV (0.250+2+20 mg/kg bw) for 21 days. Both alkaline and hOGG1-modified comet assay showed that DNA damage was more severe in rat kidneys than in liver following mycotoxin treatment. Alkaline comet assay revealed a higher intensity of DNA damage, particularly as measured by tail intensity in the kidneys. Both tail length and tail intensity were OTA dose-dependent, but in combined OTA+CIT treatment these values were similar to CIT alone and lower than in animals treated with single OTA, possibly due to induction of apoptosis. hOGG1-modified comet showed that OTA+CIT evoked greater oxidative DNA damage than single mycotoxins. RSV did not reduce DNA damage measured by alkaline comet assay, but hOGG1-modified comet showed that RSV ameliorated OTA+CIT genotoxicity in the kidneys. Apart from oxidative stress, other mechanisms of DNA damage are involved in OTA and CIT genotoxicity. In rat kidneys RSV can reduce but not overcome oxidative DNA damage induced by combined OTA and CIT.
D. Rašić; D. Želježić; N. Kopjar; Domagoj Kifer; M. Šegvić Klarić; M. Peraica. DNA damage in rat kidneys and liver upon subchronic exposure to single and combined ochratoxin A and citrinin. World Mycotoxin Journal 2019, 12, 163 -172.
AMA StyleD. Rašić, D. Želježić, N. Kopjar, Domagoj Kifer, M. Šegvić Klarić, M. Peraica. DNA damage in rat kidneys and liver upon subchronic exposure to single and combined ochratoxin A and citrinin. World Mycotoxin Journal. 2019; 12 (2):163-172.
Chicago/Turabian StyleD. Rašić; D. Želježić; N. Kopjar; Domagoj Kifer; M. Šegvić Klarić; M. Peraica. 2019. "DNA damage in rat kidneys and liver upon subchronic exposure to single and combined ochratoxin A and citrinin." World Mycotoxin Journal 12, no. 2: 163-172.
Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment. However, considering its heterogeneity, subjects with similar spirometric parameters do not necessarily have the same functional status. To overcome this limitation novel biomarkers for COPD have been investigated. Therefore, we aimed to explore the potential value of N-glycans as COPD biomarkers and to examine the individual variation of plasma protein and immunoglobulin G (IgG) glycosylation profiles in subjects with COPD and healthy controls. Both the total plasma protein and IgG N-glycome have been profiled in the total of 137 patients with COPD and 95 matching controls from Croatia. Replication cohort consisted of 61 subjects with COPD and 148 controls recruited at another Croatian medical centre. Plasma protein N-glycome in COPD subjects exhibited significant decrease in low branched and conversely, an increase in more complex glycan structures (tetragalactosylated, trisialylated, tetrasialylated and antennary fucosylated glycoforms). We also observed a significant decline in plasma monogalactosylated species, and the same change replicated in IgG glycome. N-glycans also showed value in distinguishing subjects in different COPD GOLD stages, where the relative abundance of more complex glycan structures increased as the disease progressed. Glycans also showed statistically significant associations with the frequency of exacerbations and demonstrated to be affected by smoking, which is the major risk factor for COPD development. This study showed that complexity of glycans associates with COPD, mirroring also the disease severity. Moreover, changes in N-glycome associate with exacerbation frequency and are affected by smoking. In general, this study provided new insights into plasma protein and IgG N-glycome changes occurring in COPD and pointed out potential novel markers of the disease progression and severity.
Tamara Pavić; Dario Dilber; Domagoj Kifer; Najda Selak; Toma Keser; Đivo Ljubičić; Andrea Vukić Dugac; Gordan Lauc; Lada Rumora; Olga Gornik. N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease. Journal of Translational Medicine 2018, 16, 1 -15.
AMA StyleTamara Pavić, Dario Dilber, Domagoj Kifer, Najda Selak, Toma Keser, Đivo Ljubičić, Andrea Vukić Dugac, Gordan Lauc, Lada Rumora, Olga Gornik. N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease. Journal of Translational Medicine. 2018; 16 (1):1-15.
Chicago/Turabian StyleTamara Pavić; Dario Dilber; Domagoj Kifer; Najda Selak; Toma Keser; Đivo Ljubičić; Andrea Vukić Dugac; Gordan Lauc; Lada Rumora; Olga Gornik. 2018. "N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease." Journal of Translational Medicine 16, no. 1: 1-15.
Species assigned to Aspergillus section Flavi are food contaminants and may cause mycoses. Higher humidity may favour their occurrence in indoor environments and support the biosynthesis of aflatoxin B1 (AFB1), their toxic and cancerogenic metabolite. The aim of this study was to compare the frequencies of aflatoxin-producing and non-producing Aspergilli isolated from flood affected and control area in Croatia. Additionally, comet assay was employed to evaluate their genotoxic potential. Aspergilli of interest were isolated from air (N=60) and dust (N=60) samples collected during 2016 and 2017, two and three years after flood in Eastern Croatia. Identification of the isolates was based on morphology and the partial calmodulin sequences. Microextracts prepared from fungal cultures were analysed on AFB1 content by LC/MS. Genotoxicity of extracted Aspergilli was tested in human lung adenocarcinoma cell line A549 by alkaline comet-assay. Aspergilli (Flavi) dominated in the samples collected in flood-affected area (33/40) compared to the control area (3/40) and were more frequent in the airsamples (83%). AFB1 producing abilities were confirmed only for isolates from flood affected area (10/33). Genotoxic potential measured as tail intensity (% of DNA in comet tail) was slightly higher for AFB1-negative compared to AFB1-positive extract (0.57 ±0.94 and 0.14 ± 0.31, respectively). Flood may support the occurrence of Aspergilli from section Flavi in indoor environments. Inhalation of these mycoparticles may have a harmful effect on the respiratory system of the exposed people regardless of AFB1 presence. This work has been fully supported by Croatian Science Foundation under the project MycotoxA (IP-09-2014-5982).
Daniela Jakšić; Miranda Sertić; Ana Mornar Turk; Domagoj Kifer; Nevenka Kopjar; Biljana Nigović; Maja Šegvić Klarić. Post-flood risks of inhalatory exposure to Aspergillus section Flavi. Occupational and Environmental Health 2018, 52, PA1196 .
AMA StyleDaniela Jakšić, Miranda Sertić, Ana Mornar Turk, Domagoj Kifer, Nevenka Kopjar, Biljana Nigović, Maja Šegvić Klarić. Post-flood risks of inhalatory exposure to Aspergillus section Flavi. Occupational and Environmental Health. 2018; 52 ():PA1196.
Chicago/Turabian StyleDaniela Jakšić; Miranda Sertić; Ana Mornar Turk; Domagoj Kifer; Nevenka Kopjar; Biljana Nigović; Maja Šegvić Klarić. 2018. "Post-flood risks of inhalatory exposure to Aspergillus section Flavi." Occupational and Environmental Health 52, no. : PA1196.
D. Rašić; D. Želježić; V. Micek; Domagoj Kifer; D. Jakšić; M. Peraica; N. Kopjar; M. Šegvić Klarić. Sterigmatocystin induces oxidative stress in male Wistar rats. Toxicology Letters 2018, 295, S199 -S200.
AMA StyleD. Rašić, D. Želježić, V. Micek, Domagoj Kifer, D. Jakšić, M. Peraica, N. Kopjar, M. Šegvić Klarić. Sterigmatocystin induces oxidative stress in male Wistar rats. Toxicology Letters. 2018; 295 ():S199-S200.
Chicago/Turabian StyleD. Rašić; D. Želježić; V. Micek; Domagoj Kifer; D. Jakšić; M. Peraica; N. Kopjar; M. Šegvić Klarić. 2018. "Sterigmatocystin induces oxidative stress in male Wistar rats." Toxicology Letters 295, no. : S199-S200.
Daniela Jakšić Despot; Miranda Sertić; Ana Mornar Turk; Domagoj Kifer; Biljana Nigović; Maja Šegvić Klarić. Frequency of sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-MET-STC)-producing airborne Aspergilli from flooded and unflooded area in Croatia. Toxicology Letters 2017, 280, S210 .
AMA StyleDaniela Jakšić Despot, Miranda Sertić, Ana Mornar Turk, Domagoj Kifer, Biljana Nigović, Maja Šegvić Klarić. Frequency of sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-MET-STC)-producing airborne Aspergilli from flooded and unflooded area in Croatia. Toxicology Letters. 2017; 280 ():S210.
Chicago/Turabian StyleDaniela Jakšić Despot; Miranda Sertić; Ana Mornar Turk; Domagoj Kifer; Biljana Nigović; Maja Šegvić Klarić. 2017. "Frequency of sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-MET-STC)-producing airborne Aspergilli from flooded and unflooded area in Croatia." Toxicology Letters 280, no. : S210.
Staphylococcus aureus is one of the most commonly isolated microbes in chronic rhinosinusitis (CRS) that can be complicated due to the formation of a staphylococcal biofilm. In this study, we investigated antimicrobial efficacy of single mupirocin and three types of monoterpenes (thymol, menthol and 1,8-cineole) as well as mupirocin–monoterpene combinations against S. aureus ATCC 29213 and 5 methicilin-resistant S. aureus strains (MRSA) grown in planktonic and biofilm form. MIC against planktonic bacteria as well as minimum biofilm-eliminating concentrations (MBECs) and minimum biofilm inhibitory concentrations (MBICs) were determined by TTC and MTT reduction assay, respectively. The MICs of mupirocin (0.125–0.156 μg ml−1) were three orders of magnitude lower than the MICs of monoterpenes, which were as follows: thymol (0.250–0.375 mg ml−1) > menthol (1 mg ml−1) > 1,8-cineole (4–8 mg ml−1). Mupirocin-monoterpene combinations showed indifferent effect as compared with MICs of single substances. Mupirocin (0.016–2 mg ml−1) failed to destroy the biofilm. The MBECs of thymol and menthol were two- to sixfold higher than their MICs, while 1,8-cineole exerted a weak antibiofilm effect with MBECs 16- to 64-fold higher than MICs. Mixture of mupirocin and 1,8 cineole exerted a potentiated biofilm-eliminating effect, mupirocin–menthol showed antagonism, while effect of thymol–mupirocin mixture was inconclusive. MBICs of antimicrobials were close to their MICs, except 1,8-cineole, MBIC was about three- to fivefold higher. Dominant synergy was observed for mixtures of mupirocin and menthol or thymol, whereas mupirocin-1,8-cineol exerted an indifferent or additive biofilm inhibitory effect. Particular combinations of mupirocin and the monoterpenes could be applied in CRS therapy in order to eliminate or prevent bacterial biofilm growth.
Domagoj Kifer; Vedran Mužinić; Maja Šegvić Klarić. Antimicrobial potency of single and combined mupirocin and monoterpenes, thymol, menthol and 1,8-cineole against Staphylococcus aureus planktonic and biofilm growth. The Journal of Antibiotics 2016, 69, 689 -696.
AMA StyleDomagoj Kifer, Vedran Mužinić, Maja Šegvić Klarić. Antimicrobial potency of single and combined mupirocin and monoterpenes, thymol, menthol and 1,8-cineole against Staphylococcus aureus planktonic and biofilm growth. The Journal of Antibiotics. 2016; 69 (9):689-696.
Chicago/Turabian StyleDomagoj Kifer; Vedran Mužinić; Maja Šegvić Klarić. 2016. "Antimicrobial potency of single and combined mupirocin and monoterpenes, thymol, menthol and 1,8-cineole against Staphylococcus aureus planktonic and biofilm growth." The Journal of Antibiotics 69, no. 9: 689-696.