Accession Number : ADA615638


Title :   High-Throughput Nano-Biofilm Microarray for Antifungal Drug Discovery


Descriptive Note : Journal article


Corporate Author : ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX


Personal Author(s) : Srinivasan, Anand ; Leung, Kai P ; Lopez-Ribot, Jose L ; Ramasubramanian, Anand K


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a615638.pdf


Report Date : 25 Jun 2013


Pagination or Media Count : 12


Abstract : Micro- and nanoscale technologies have radically transformed biological research from genomics to tissue engineering, with the relative exception of microbial cell culture, which is still largely performed in microtiter plates and petri dishes. Here, we present nanoscale culture of the opportunistic fungal pathogen Candida albicans on a microarray platform. The microarray consists of 1,200 individual cultures of 30 nl of C. albicans biofilms ( nano-biofilms ) encapsulated in an inert alginate matrix. We demonstrate that these nano-biofilms are similar to conventional macroscopic biofilms in their morphological, architectural, growth, and phenotypic characteristics. We also demonstrate that the nano-biofilm microarray is a robust and efficient tool for accelerating the drug discovery process: (i) combinatorial screening against a collection of 28 antifungal compounds in the presence of immunosuppressant FK506 (tacrolimus) identified six drugs that showed synergistic antifungal activity, and (ii) screening against the NCI challenge set small-molecule library identified three heretofore-unknown hits. This cell-based microarray platform allows for miniaturization of microbial cell culture and is fully compatible with other high-throughput screening technologies.


Descriptors :   *PATHOGENIC MICROORGANISMS , ANTIBIOTICS , BIOASSAY , BIOMATERIALS , BIOMEDICAL ENGINEERING , CANDIDA , CELLS(BIOLOGY) , CLINICAL MEDICINE , CULTURES(BIOLOGY) , FUNGICIDES , GENOMICS , INFECTIOUS DISEASES , MORTALITY RATE , TISSUES(BIOLOGY)


Subject Categories : Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE