Enhanced resistance of Trichoderma harzianum LZDX-32-08 to hygromycin B induced by sea salt
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ORIGINAL RESEARCH PAPER
Enhanced resistance of Trichoderma harzianum LZDX-3208 to hygromycin B induced by sea salt Xijia Yu . Huiling Wei . Xianrui Liu . Dong Liu . Aili Fan
. Haijia Su
Received: 30 April 2020 / Accepted: 18 August 2020 Ó Springer Nature B.V. 2020
Abstract Objectives To determine the effect of sea salt on the resistance of Trichoderma harzianum LZDX-32-08 to hygromycin B and speculate the possible mechanisms involved via transcriptome analysis. Results Sea salt addition in media to simulate marine environment significantly increased the tolerance of marine-derived fungus Trichoderma harzianum LZDX-32-08 to hygromycin B from 40 to 500 lg/ ml. Meanwhile, sea salt addition also elicited the hygromycin B resistance of 5 other marine or terrestrial fungi. Transcriptomic analyses of T. harzianum cultivated on PDA, PDA supplemented with sea salt and PDA with both sea salt and hygromycin B revealed that genes coding for P-type ATPases, multidrug resistance related transporters and
acetyltransferases were up-regulated, while genes coding for Ca2?/H? antiporter and 1,3-glucosidase were down-regulated, indicating probable increased efflux and inactivation of hygromycin B as well as enhanced biofilm formation, which could jointly contribute to the drug resistance. Conclusions Marine environment or high ion concentration in the environment could be an importance inducer for antifungal resistance. Possible mechanisms and related key genes were proposed for understanding the molecular basis and overcoming this resistance.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10529-020-02994-y) contains supplementary material, which is available to authorized users.
Introduction
X. Yu H. Wei X. Liu A. Fan (&) H. Su Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, North Third Ring Road 15, Chaoyang District, Beijing 100029, People’s Republic of China e-mail: [email protected] D. Liu State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, People’s Republic of China
Keywords Antifungal resistance Hygromycin B Sea salt Transcriptome Trichoderma harzianum
About 1.5–2 million people die of fungal infection each year (Denning and Bromley 2015). These numbers increased steadily in recent decades (Sekyere and Asante 2018). Worse still, antifungal resistance became a big challenge due to consistent use of limited antimicrobials (Denning and Bromley 2015). Thus, it is extremely urgent to obtain a better understanding of resistance mechanisms in order to reverse the resistance or provide novel targets for drug development. Previous studies revealed three main mechanisms
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including changes in drug target sites, activation of drug efflux and formation of biofilms (Sekyere and Asante 2018). Hygromycin B (HYG) is an aminoglycoside antibiotic that inhibits protein synthesis by stabilizing
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