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Shaheer Hasan Khan,1,* Hina Younus,1,* Khaled S Allemailem,2 Ahmad Almatroudi,2 Faris Alrumaihi,2 Abdulmohsen M Alruwetei,2 Mohammed A Alsahli,2 Arif Khan,3 Masood Alam Khan3 1Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India; 2Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia; 3Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraidah, 51452, Saudi Arabia*These authors contributed equally to this workCorrespondence: Masood Alam KhanDepartment of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, KSA 51452 Tel +966-507059437Fax +966-63801628Email a_khan@qu.edu.saBackground: Fungal infections are becoming more prevalent and threatening because of the continuous emergence of azole-resistant fungal infections. The present study was aimed to assess the activity of free Methylglyoxal (MG) or MG-conjugated chitosan nanoparticles (MGCN) against fluconazole-resistant Candida albicans.Materials and Methods: A novel formulation of MGCN was prepared and characterized to determine their size, shape and polydispersity index. Moreover, the efficacy of fluconazole or MG or MGCN was determined against intracellular C. albicans in macrophages and the systematic candidiasis in a murine model. The safety of MG or MGCN was tested in mice by analyzing the levels of hepatic and renal toxicity parameters.Results: Candida albicans did not respond to fluconazole, even at the highest dose of 20 mg/kg, whereas MG and MGCN effectively eliminated C. albicans from the macrophages and infected mice. Mice in the group treated with MGCN at a dose of 10 mg/kg exhibited a 90% survival rate and showed the lowest fungal load in the kidney, whereas the mice treated with free MG at the same dose exhibited 50% survival rate. Moreover, the administration of MG or MGCN did not induce any liver and kidney toxicity in the treated mice.Conclusion: The findings of the present work suggest that MGCN may be proved a promising therapeutic formulation to treat azole-resistant C. albicans infections.Keywords: chitosan nanoparticles, fluconazole-resistant, systemic Candidiasis, methylglyoxal

The Arabian Camelus dromedarius contains significant concentration of eye lens ��-crystallin. This enzyme is also present in other life forms including humans, however in lower catalytic amounts. The recombinant camel ��-crystallin was expressed in the E. coli BL21 (DE3) pLysS strain and purified using HisTrap column. The Km of the enzyme for 9,10-phenanthrenequinone (9,10-PQ) substrate and NADPH cofactor was determined to be 11.66 and 50.93 ��M, respectively. The Vmax for 9,10-PQ and NADPH was obtained as 23.19 and 19.98 ��M min���1, respectively. The optimum activity of the purified enzyme was found to be at pH 6.0 and at 55 ��C. Different physico-chemical parameters were analysed including instability index (II), aliphatic index (AI) and the GRAVY index to establish proper characterization. The sequence of the recombinant ��-crystallin was subjected to homology modelling using SWISS-MODEL webserver followed by validation of the modelled target structure. The evaluation of the modelled ��-crystallin was performed by several parameters including Ramachandran plot, Z-score values followed by molecular dynamics (MD) simulation. The cumulative analysis of the physico-chemical, quantitative, qualitative and the essential dynamics of simulation of ��-crystallin and its complexes with 9,10-PQ and NADPH helped in verifying the acceptable quality and stability of the ��-crystallin structure. Communicated by Ramaswamy H. Sarma