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In vitro-induced erythromycin resistance facilitates cross-resistance to the novel fluoroketolide, solithromycin, in Staphylococcus aureus.

Authors :
Weiming Yao
Guangjian Xu
Bing Bai
Hongyan Wang
Minggui Deng
Jinxin Zheng
Duoyun Li
Xiangbin Deng
Xiaojun Liu
Zhiwei Lin
Zhong Chen
Guiqiu Li
Qiwen Deng
Zhijian Yu
Source :
FEMS Microbiology Letters; Jun2018, Vol. 365 Issue 12, p1-6, 6p
Publication Year :
2018

Abstract

The aim of this study was to determine whether in vitro induced erythromycin resistance facilitates the cross-resistance to the novel fluoroketolide, solithromycin, in Staphylococcus aureus. Four strains of methicillin-susceptible S. aureus strains S2, S3, S5 and S7 were successfully induced to establish erythromycin-resistant strains by continuous in vitro culture with erythromycin. Mutations at drug binding sites were shown to increase the minimal inhibitory concentrations for ketolides, including telithromycin and the novel compound solithromycin, but did not increase for lincosamides, chloramphenicols or oxazolidinones. In S2-, S5- and S7-derived strains, L22 protein mutations occurred first, resulting in a low level of cross-resistance to ketolides (≤4 μg/mL). The L4 protein mutations were dependent on the L22 protein, resulting in high-level cross-resistance to ketolides (≥8 μg/mL). In S3-derived strains, high levels of cross-resistance occurred concurrently in the 23S rRNA domains II/V and the L22 protein. Hence, long-term exposure of erythromycin results in resistance to ketolides in S. aureus through drug binding site mutations. These results demonstrate that since erythromycin has been used clinically for a long time, it is necessary to carefully evaluate the rewards and risks when prescribing solithromycin for the treatment of infectious diseases. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03781097
Volume :
365
Issue :
12
Database :
Complementary Index
Journal :
FEMS Microbiology Letters
Publication Type :
Academic Journal
Accession number :
130409090
Full Text :
https://doi.org/10.1093/femsle/fny116