In vitro-induced erythromycin resistance facilitates cross-resistance to the novel fluoroketolide, solithromycin, in Staphylococcus aureus. Issue 12 (3rd May 2018)

• Record Type: Journal Article
• Authors: Yao, Weiming; Xu, Guangjian; Bai, Bing; Wang, Hongyan; Deng, Minggui; Zheng, Jinxin; Li, Duoyun; Deng, Xiangbin; Liu, Xiaojun; Lin, Zhiwei; Chen, Zhong; Li, Guiqiu; Deng, Qiwen; Yu, Zhijian
• Is Part Of: FEMS microbiology letters. Volume 365:Issue 12(2018:Jun.)
• Publication Date: 2018-05-03
• Subjects: drug resistance -- solithromycin -- Staphylococcus aureus -- mutation -- cross-resistance -- erythromycin; Microbiology -- Periodicals; 579
• DOI: 10.1093/femsle/fny116
• Languages: English
• ISSNs: 0378-1097

Abstract

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 : Long-term exposure of erythromycin facilitates the resistance to solithromycin in S. aureus .