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Front. Microbiol. | doi: 10.3389/fmicb.2018.03142

Linezolid in combination with azoles induced synergistic effects against Candida albicans and protected Galleria mellonella against experimental candidiasis

Mengjiao Lu1, 2, Xinmei Yang3, Cuixiang Yu4, Ying Gong1, Lei Yuan2 and  Shujuan Sun3*
  • 1School of Pharmaceutical Sciences, Shandong University, China
  • 2Department of Pharmacy, Dongying People’s Hospital, China
  • 3Department of Pharmacy, Qianfoshan Hospital Affiliated to Shandong University, China
  • 4Department of Respiration Medicine, Qianfoshan Hospital Affiliated to Shandong University, China

The incidence of resistant Candida isolates has increased continuously in recent decades, especially Candida albicans. To overcome the resistance, the research on antifungal sensitizers has attracted considerable attention. Linezolid was found to inhibit the growth of Pythium insidiosum and synergize with amphotericin B against Cryptococcus neoformans. The objective of this study was to determine the interactions of linezolid and azoles against C. albicans in vitro and in vivo. In vitro, linezolid combined with azoles induced the synergistic effects not only against some susceptible C. albicans isolates but also against all tested resistant C. albicans isolates. For all resistant isolates, exposure to the combination of linezolid with azoles induced a significant decrease in the minimum inhibitory concentrations of azoles, from > 512 μg/mL to 0.5-1 μg/mL for fluconazole, from > 16 μg/mL to 0.25-1 μg/mL for itraconazole, and from > 16 μg/mL to 0.03-0.25 μg/mL for voriconazole. Additionally, linezolid synergized with fluconazole against biofilms that were preformed for ≤ 12 h from both susceptible and resistant C. albicans, and the sessile minimum inhibitory concentration of fluconazole decreased from > 1024 μg/mL to 1-4 μg/mL. In vivo, linezolid plus azoles prolonged the survival rate of infected Galleria mellonella larvae twofold compared with the azole monotherapy group; significantly decreased the fungal burden of the infected larvae; and reduced the damage of resistant C. albicans to the larval tissue. These findings will contribute to antifungal agent discovery and new approaches for the treatment of candidiasis caused by C. albicans.

Keywords: linezolid, Azoles, Synergism, Candida albians, Galleria mellonella model

Received: 05 Aug 2018; Accepted: 04 Dec 2018.

Edited by:

Farhat Afrin, Taibah University, Saudi Arabia

Reviewed by:

Masoomeh Shams-Ghahfarokhi, Tarbiat Modares University, Iran
Elena De Carolis, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Italy  

Copyright: © 2018 Lu, Yang, Yu, Gong, Yuan and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Shujuan Sun, Department of Pharmacy, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong Province, China, sunshujuan888@163.com