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

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

doi:10.3389/fmicb.2019.00034

Wenyue Da, Changzhong Wang + Show 5 more

Open Access

https://doi.org/10.3389/fmicb.2019.00034

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Abstract

Candida albicans 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 C. albicans, and the underlying mechanism might be likely to be associated with β-glucan synthesis and transportation (Shao et al., 2017). In the present experiment, we used a standard C. albicans isolate and a phr1 mutant (phr1−/−) 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 C. albicans SC5314 but became futile in phr1−/−. Although the minimum inhibitory concentrations (MICs) of SH were comparable in the two Candida strains used, phr1−/− appeared to be more susceptible to SH compared with C. albicans SC5314 in biofilms (64 versus 512 μg/mL). The peak areas of SH decreased markedly by 71.6, 38.2, and 62.6% in C. albicans SC5314 and by 70% and 53.2% in phr1−/− 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 C. albicans SC5314 and phr1−/−. 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.

Highlights

Candida albicans, a frequently isolated opportunistic pathogen, presents with two opposite faces, i.e., an ordinary resident on the skin and mucosal layers of healthy people, and a fatal invader causing deep-seated systematic infections in compromised individuals (Poulain, 2013)
In terms of aforementioned physical interaction of sodium houttuyfonate (SH) with β-1,3-glucan, it is very likely that SH can remodel C. albicans cell wall and unmask β-1,3-glucan
SH Disturbance Was Blocked by β-1,3-Glucan via Cell Wall Remodeling

Summary

Introduction

A frequently isolated opportunistic pathogen, presents with two opposite faces, i.e., an ordinary resident on the skin and mucosal layers of healthy people, and a fatal invader causing deep-seated systematic infections in compromised individuals (Poulain, 2013). C. albicans possesses an arsenal of effective tools to overcome extraneous scavengers (especially antifungal drugs). These tools include the secretions of invasive enzyme (such as secreted aspartyl proteinases). Since there are multiple factors influencing C. albicans resistance, it becomes necessary to develop novel drugs as synergists to improve the antifungal effects of conventional agents. It is economic and time-saving to exploit drugs with antifungal potentials which usually have anti-inflammatory, anti-tumor, anti-virus, and anti-bacterial functions (Liu et al, 2011; Lu et al, 2017). We still don’t know enough about the antifungal mechanism of SH

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