Proteomic profiling of the antifungal drug response of Aspergillus fumigatus to voriconazole

2017-10-01
Amarsaikhan, Nansalmaa
Albrecht-Eckardt, Daniela
Sasse, Christoph
Braus, Gerhard H.
Ögel, Zümrüt Begüm
Kniemeyer, Olaf
Antifungal resistance is an emerging problem and one of the reasons for treatment failure of invasive aspergillosis (IA). Voriconazole has become a standard therapeutic for the treatment of this often fatal infection. We studied the differentially expressed proteins as a response of Aspergillus fumigatus to voriconazole by employing the two-dimensional difference gel electrophoresis (DIGE) technique. Due to addition of drug, a total of 135 differentially synthesized proteins were identified by MALDI-TOF/TOF-mass spectrometry. In particular, the level of proteins involved in the general stress response and cell detoxification increased prominently. In contrast, cell metabolism and energy proteins were down-regulated, which suggests the cellular effort to maintain balance in energy utilization while trying to combat the cellular stress exerted by the drug. We detected several so-far uncharacterized proteins which may play a role in stress response and drug metabolism and which could be future targets for antifungal treatment. A mutant strain, which is deleted in the cross-pathway control gene cpcA, was treated with voriconazole to investigate the contribution of the general control of amino acid biosynthesis to drug resistance. We compared the mutant strain's protein expression profile with the wild-type strain. The absence of CpcA led to an increased resistance to voriconazole and a reduced activation of some general stress response proteins, while the transcript level of the triazole target gene ergllA (cyp51A) remained unchanged. In contrast, the sensitivity of strain Delta cpcA to terbinafine and amphotericin B was slightly increased. These findings imply a role of CpcA in the cellular stress response to azole drugs at the post transcriptional level.
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY

Suggestions

In vitro antibiotic release from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) rods
Gursel, I; Yagmurlu, F; Korkusuz, F; Hasırcı, Vasıf Nejat (2002-03-01)
Provision and maintenance of adequate concentrations of antibiotics at infection sites is very important in treating highly resistant infections. For diseases like implant related osteomyelitis (IRO) it is best to provide this locally via implanted drug formulations, as systemic administration of the antibiotic may not be effective due to damaged vasculature. In this study, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) rods containing 7, 14 and 22% (mol) 3-hydroxyvalerate were loaded with sulbactam:ce...
Genomic characterization of pseudomonas aeruginosa clinical isolates by pulsed field gel electrophoresis method
Alipour Ghorbani, Nader; Yıldız, Fatih; Durmaz, Rıza; Department of Biotechnology (2014)
Pseudomonas aeruginosa is a common cause of nosocomial infections, particularly in intensive care units (ICUs), bronchoscopy, oncology, and urology. The aim of this study was to characterize P. aeruginosa clinical isolates clonally relatedness by pulsed-field gel electrophoresis (PFGE) typing and it’s cut off value determination. We did retrospective study and analyzed genotypically a collection of 58 clinical isolates recovered during the period 2006–2011 from MESA private hospital microbiology department’...
In Situ, In Vitro and In Vivo evaluation of effectiveness of new treatment approaches involving controlled drug delivery systems in cartilage degenerations
Aydın, Özlem; Keskin, Dilek; Tezcaner, Ayşen; Department of Engineering Sciences (2011)
Osteoarthritis (OA) is a degenerative joint disease which has yet no complete treatment with medication. Doxycycline, a well-known antibiotic, has been shown to prevent matrixmetallopreoteinases-MMPs, indicating potency on OA treatment. However, long term systemic use can cause side effects on other tissues. This study aimed to develop controlled drug delivery systems of doxycycline/doxycycline-chondroitin sulfate (D/D-CS) in the form of PCL microspheres for providing a better and new treatment approach via...
Molecular analysis of beta lactamases in clinical acinetobacter baumannii ısolates from intensive care units
Güçlü Üsküdar, Aylin; Gözen, Ayşe Gül; Department of Biology (2011)
Carbapenem resistance in Acinetobacter baumannii is a growing public health concern and represents a serious problem for treatment of the infection. Several carbapenem-hydrolysing β-lactamases have been identified from A. baumannii so far. In this study carbapenem resistance in A.baumannii strains recovered from intensive care units of Gulhane Military Medical Academy, Turkey, were investigated via multiplex PCR and with parallel phenotypic tests. From June 2006 to January 2010, 138 clinical A. baumannii is...
Development and characterization of cortisone derivative drugcarrying polymeric microspheres
Öcal, Yiğit; Keskin, Dilek; Özen, Seza; Department of Biomedical Engineering (2011)
In this study, it is aimed to develop an injectable controlled release system of PCL and P(L,DL)LA microspheres loaded with TA and/or Ral for local treatment of rheumatoid arthritis which will avoid from systemic side effects of traditional administration and eliminate problems caused by direct local injections. Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder that most commonly causes inflammation and tissue damage in joints and tendon sheaths. Current strategies for the disease are ma...
Citation Formats
N. Amarsaikhan, D. Albrecht-Eckardt, C. Sasse, G. H. Braus, Z. B. Ögel, and O. Kniemeyer, “Proteomic profiling of the antifungal drug response of Aspergillus fumigatus to voriconazole,” INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, pp. 398–408, 2017, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/51004.