AUTHOR=Da Wenyue , Shao Jing , Li Qianqian , Shi Gaoxiang , Wang Tianming , Wu Daqiang , Wang Changzhong 

TITLE=Physical Interaction of Sodium Houttuyfonate With β-1,3-Glucan Evokes Candida albicans Cell Wall Remodeling

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00034

DOI=10.3389/fmicb.2019.00034

ISSN=1664-302X

ABSTRACT=<p><italic>Candida albicans</italic> is a commonly isolated opportunistic yeast and can endanger immune-compromised human health. As increasingly isolated strains present resistance to currently used antifungals, it is necessary to develop novel antimycotics. In a previous study, sodium houttuyfonate (SH) alone or in combination with fluconazole revealed relatively strong antifungal potential against <italic>C. albicans</italic>, and the underlying mechanism might be likely to be associated with β-glucan synthesis and transportation (<xref ref-type="bibr" rid="B39">Shao et al., 2017</xref>). In the present experiment, we used a standard <italic>C. albicans</italic> isolate and a phr1 mutant (<italic>phr1</italic>−/−) to investigate the interaction of SH with β-glucan, one of the critical components in cell wall and biofilm matrix. We showed that lyticase was the most effective enzyme that could significantly increase the antifungal inhibition of SH at 64 μg/mL in <italic>C. albicans</italic> SC5314 but became futile in <italic>phr1</italic>−/−. Although the minimum inhibitory concentrations (MICs) of SH were comparable in the two <italic>Candida</italic> strains used, <italic>phr1</italic>−/− appeared to be more susceptible to SH compared with <italic>C. albicans</italic> SC5314 in biofilms (64 versus 512 μg/mL). The peak areas of SH decreased markedly by 71.6, 38.2, and 62.6% in <italic>C. albicans</italic> SC5314 and by 70% and 53.2% in <italic>phr1</italic>−/− by ultra-performance liquid chromatography (UPLC) analysis after co-incubation of SH with laminarin, extracellular matrix (EM) and cell wall. The chitin appeared to not interact with SH. We further demonstrated that sub-MIC SH (8 μg/mL) was able to induce cell wall remodeling by unmasking β-1,3-glucan and chitin in both <italic>C. albicans</italic> SC5314 and <italic>phr1</italic>−/−. Based on these findings, we propose that β-1,3-glucan can block the entrance of SH through non-specific absorption, and then the fungus senses the interaction of SH with β-1,3-glucan and exposes more β-1,3-glucan that contributes to SH blocking in turn.</p>