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

FEMS Microbiol Lett 2018 06;365(12)

Department of Infectious Diseases and Shenzhen Key Lab for Endogenous Infection, Shenzhen Nanshan Hospital of Shenzhen University, No 89, Taoyuan Road, Nanshan District, Shenzhen 518052, China.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1093/femsle/fny116DOI Listing
June 2018
30 Reads

Publication Analysis

Top Keywords

erythromycin resistance
12
l22 protein
12
staphylococcus aureus
8
solithromycin staphylococcus
8
fluoroketolide solithromycin
8
cross-resistance ketolides
8
aureus strains
8
drug binding
8
novel fluoroketolide
8
protein mutations
8
facilitates cross-resistance
8
resistance facilitates
8
cross-resistance novel
8
strains
5
cross-resistance
5
dependent l22
4
solithromycin increase
4
increase lincosamides
4
protein high-level
4
mutations dependent
4

Similar Publications