title: Glucose directly promotes antifungal resistance in the fungal pathogen, Candida spp.
abstract: Effects of glucose on the susceptibility of antifungal agents were investigated against Candida spp. Increasing the concentration of glucose decreased the activity of antifungal agents; voriconazole was the most affected drugs followed by amphotericin B. No significant change has been observed for anidulafungin. Biophysical interactions between antifungal agents with glucose molecules were investigated using isothermal titration calorimetry, Fourier transform infrared, and (1)H NMR. Glucose has a higher affinity to bind with voriconazole by hydrogen bonding and decrease the susceptibility of antifungal agents during chemotherapy. In addition to confirming the results observed in vitro, theoretical docking studies demonstrated that voriconazole presented three important hydrogen bonds and amphotericin B presented two hydrogen bonds that stabilized the glucose. In vivo results also suggest that the physiologically relevant higher glucose level in the bloodstream of diabetes mellitus mice might interact with the available selective agents during antifungal therapy, thus decreasing glucose activity by complex formation. Thus, proper selection of drugs for diabetes mellitus patients is important to control infectious diseases.
authors: From the Department of Chemistry, Central Research Facility, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India, the Department of Microbiology, Vidyasagar University, Midnapore 721102, West Bengal, India mandalsm@gmail.com.
authors: Santi M
authors: SM
authors: Mandal
authors: From the Department of Chemistry, Central Research Facility, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors: Denial
authors: D
authors: Mahata
authors: the Programa de Pós-Graduação em Biotecnologia, Centro de Pesquisas Bioquímicas e Biofísicas, Universidade Católica Dom Bosco, Campo Grande 79117-900, Brazil, and.
authors: Ludovico
authors: L
authors: Migliolo
authors: From the Department of Chemistry, Central Research Facility, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors: Aditya
authors: A
authors: Parekh
authors: From the Department of Chemistry, Central Research Facility, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors: Partha S
authors: PS
authors: Addy
authors: From the Department of Chemistry, Central Research Facility, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors: Mahitosh
authors: M
authors: Mandal
authors: From the Department of Chemistry, Central Research Facility, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India, absk@chem.iitkgp.ernet.in.
authors: Amit
authors: A
authors: Basak
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry*; D055592:Biophysical Phenomena; D002151:Calorimetry; D002175:Candida / Q000187:drug effects* / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000935:Antifungal Agents; D005947:Glucose
keywords: Antibiotic Resistance; Candida albicans; Diabetes; Drug Action; Glucose