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Inducible Expression of both ermB and ermT Conferred High Macrolide Resistance in Streptococcus gallolyticus subsp.
Meixia Li1, Chao Cai2, Juan Chen3
1College of Veterinary Medicine, Huazhong Agricultural University, 1st Shizishan Street, Wuhan 430070, China. mislimeixia@126.com.
Abstract:
Streptococcus gallolyticus subsp. pasteurianus is an under-recognized pathogen and zoonotic agent causing opportunistic infections in humans. Despite increasing recognition of this subspecies as a cause for human infectious diseases, limited information is known about its antibiotic resistance mechanism. In this study, we aim to identify the molecular mechanism underlying the high macrolide resistance of six S. gallolyticus subsp. pasteurianus isolates from dead ducklings collected in several natural outbreaks in China during 2010-2013. All isolates exhibited multi-drug resistance including high macrolide resistance (MIC ≥ 1024 mg/L for erythromycin, and 512 mg/L for clarithromycin). Efflux-encoding mefA and mefE genes were not detectable in these isolates. The presence of 23S rRNA mutations in specific isolates did not significantly change macrolide MICs. No nucleotide substitutions were found in genes encoding ribosomal proteins L4 or L22. The ermB and ermT genes were found in the genomes of all isolates. These two genes were acquired independently in one highly virulent isolate AL101002, and clustered with Tn916 and IS1216, respectively. The expression of both ermB and ermT in all isolates was erythromycin inducible and yielded comparable macrolide MICs in all six isolates. Taken together, inducible expression of both ermB and ermT conferred high macrolide resistance in these S. gallolyticus subsp. pasterianus isolates. Our findings reveal new macrolide resistance features in S. gallolyticus subsp. pasteurianus by both ermB and ermT.
Insights
High macrolide resistance in Streptococcus gallolyticus subsp. pasteurianus is linked to the inducible expression of both ermB and ermT genes. These findings reveal novel resistance mechanisms in this emerging zoonotic pathogen.
Area of Science:
- Veterinary Microbiology
- Antimicrobial Resistance
- Molecular Biology
Background:
- Streptococcus gallolyticus subsp. pasteurianus is an emerging zoonotic pathogen causing opportunistic infections.
- Limited knowledge exists regarding the antibiotic resistance mechanisms of this bacterium.
- This study focuses on understanding high macrolide resistance in isolates from avian outbreaks.
Purpose of the Study:
- To identify the molecular basis of high macrolide resistance in six S. gallolyticus subsp. pasteurianus isolates.
- To investigate the role of specific genes and mutations in conferring resistance.
- To elucidate novel macrolide resistance features in this subspecies.
Main Methods:
- Whole-genome sequencing of six S. gallolyticus subsp. pasteurianus isolates.
- Detection of antibiotic resistance genes, including mefA, mefE, ermB, and ermT.
- Analysis of mutations in 23S rRNA and ribosomal protein genes (L4, L22).
- Assessment of gene expression and inducibility.
Main Results:
- All isolates displayed multi-drug resistance, with high macrolide resistance (MIC ≥ 512 mg/L).
- The ermB and ermT genes were present in all isolates and showed erythromycin inducibility.
- No significant macrolide resistance was associated with 23S rRNA mutations or ribosomal protein gene substitutions.
- The ermB and ermT genes were independently acquired and located near mobile genetic elements.
Conclusions:
- Inducible expression of both ermB and ermT genes is responsible for high macrolide resistance in these S. gallolyticus subsp. pasteurianus isolates.
- This study reveals dual ermB and ermT gene involvement as a novel macrolide resistance mechanism in this pathogen.
- Findings contribute to understanding antimicrobial resistance in a significant zoonotic agent.
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