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. 2019 May 30;9(1):8087.
doi: 10.1038/s41598-019-44298-w.

A novel anti Candida albicans drug screening system based on high-throughput microfluidic chips

Le Qiang  1 , Jing Guo  2 , Yingkuan Han  1 , Jianfeng Jiang  3 , Xiaowen Su  4 , Hong Liu  4   5 , Qingguo Qi  6 , Lin Han  7
Affiliations

A novel anti Candida albicans drug screening system based on high-throughput microfluidic chips

Le Qiang et al. Sci Rep. .

Abstract

Due to the antibacterial resistance crisis, developing new antibacterials is of particular interest. In this study, we combined the antifungal drug amphotericin B with 50,520 different small molecule compounds obtained from the Chinese National Compound Library in an attempt to improve its efficacy against Candida albicans persister cells. To systematically study the antifungal effect of each compound, we utilized custom-designed high-throughput microfluidic chips. Our microfluidic chips contained microchannels ranging from 3 µm to 5 µm in width to allow Candida albicans cells to line up one-by-one to facilitate fluorescence-microscope viewing. After screening, we were left with 10 small molecule compounds that improved the antifungal effects of amphotericin B more than 30% against Candida albicans persister cells.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
(a) The fabrication process of the drug-screening microfluidic chip; (b) The layout; (c) Photo of the microfluidic chip; (d) SEM microscope photo of the 3-µm microchannel; (e) The 4-µm microchannel; (f) The 5-µm microchannel; (g) The 6-µm microchannel; (h) System sketch. We thank Longer Precision Pump Co., Ltd. China for the authorization to use the pump photo.
Figure 2
Figure 2
The comparison of Candida albicans in traditonal culture and microfluidic chips. (a) Fluorescence microscope view of normal Candida albicans; (b) Fluorescence microscope view of Candida albicans in microchannels; (c) SEM view of normal Candida albicans; (d) SEM view of Candida albicans in microchannels.
Figure 3
Figure 3
Candida albicans cultured in a microfluidic chip as seen under SEM at different magnifications (a–c) and fluorescent microscopy at (d) t = 0, (e) t = 18 h, (f) t = 36 h. One hour after new drug import into microchannels, Candida albicans persisters in a microfluidic chip under fluorescent microscopy at (g) t = 1 h, (h) t = 3 h, and (i) t = 6 h (The four red arrows identify the persisters.) Candida albicans LIVE/DEAD® staining after drug exposure in a microfluidic chip at (j) t = 1 h, (k) t = 3 h, and (l) t = 6 h.
Figure 4
Figure 4
Surviving Candida albicans persisters after treatment with (a) Normal amphotericin B and (b) Amphotericin B in combination with small molecule compounds. The red arrows point to the persisters. (c,d) Are the LIVE-DEAD® fluorescent images corresponding to (a,b).
Figure 5
Figure 5
10 small molecule compounds improve the fungicidal effect of amphotericin B by more than 30% against Candida albicans persister cells.
See this image and copyright information in PMC

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