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Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Increase of macrolide resistance among Streptococcus pyogenes pharyngitis driven by a mef(A)-msr(D)/emm2-ST55 lineage
Ana Friães1, Rafael Mamede1,2, Beatriz Santos1
1Instituto de Microbiologia, Faculdade de Medicina,Universidade de Lisboa, Lisbon, Portugal.
Abstract:
Increases in macrolide resistance occurred recently among Streptococcus pyogenes (Group A Streptococcus, GAS) in some countries. While the importance of monitoring the clinical and molecular epidemiology of non-invasive GAS is increasingly recognized, most surveillance focuses on invasive infections, since culture is rarely performed in tonsillo-pharyngitis. We determined the antimicrobial susceptibility and characterized the macrolide-resistant lineages of 2,002 pharyngeal isolates recovered in a Portuguese hospital in 2014-2019. There were seasonal variations in the numbers of recovered isolates, with peaks shifting between March-July and October-December, but consistently low numbers in August and September. Macrolide-resistant and macrolide-susceptible GAS presented independent seasonal and clonal dynamics, with resistant isolates showing lower genetic diversity and minimal overlap with susceptible lineages. Overall, 84 (4%), 77 (4%), and 52 (3%) isolates were resistant to erythromycin, clindamycin, and tetracycline, respectively. Until 2018, macrolide resistance was mainly due to an internationally disseminated emm77-ST63 lineage carrying erm(A) and tet(O) in ICESp2905 and an emm75-ST49 lineage carrying mef(A)-msr(D) in a novel ɸ1207.3 variant. In 2019, resistance peaked at 9% due to the rapid expansion of mef(A)-msr(D)-positive emm2-ST55 isolates, replacing previous lineages. Other minor resistant lineages carried mostly erm(B) in a diversity of mobile genetic elements, including emm75-ST150, emm9-ST75, emm11-ST403, emm12-ST36, emm76-ST50, and emm77-ST399 [erm(T)]. Tetracycline resistance was associated with the genes tet(M) and tet(O), in most cases co-located in the same genetic elements as the erm genes. This study reveals clonal changes among macrolide-resistant GAS driving fluctuations in macrolide resistance and associated phenotypes.
Insights
Macrolide resistance in Group A Streptococcus (GAS) pharyngeal isolates increased due to clonal shifts, with specific lineages like emm2-ST55 dominating in 2019. Monitoring non-invasive GAS epidemiology is crucial for understanding resistance dynamics.
Area of Science:
- Microbiology
- Epidemiology
- Molecular Biology
Background:
- Macrolide resistance in *Streptococcus pyogenes* (Group A Streptococcus, GAS) is a growing concern.
- Current surveillance often overlooks non-invasive GAS infections, focusing primarily on invasive cases.
- Understanding the epidemiology of antimicrobial resistance in pharyngeal GAS is essential.
Purpose of the Study:
- To determine the antimicrobial susceptibility of pharyngeal GAS isolates.
- To characterize the molecular epidemiology of macrolide-resistant GAS lineages.
- To investigate clonal dynamics and seasonal variations in GAS resistance.
Main Methods:
- Analysis of 2,002 pharyngeal GAS isolates collected in Portugal from 2014-2019.
- Antimicrobial susceptibility testing for erythromycin, clindamycin, and tetracycline.
- Molecular characterization of macrolide-resistant lineages, including gene identification and mobile genetic element analysis.
Main Results:
- Overall resistance rates: 4% erythromycin, 4% clindamycin, 3% tetracycline.
- Dominant lineages shifted over time, with *emm*77-ST63 and *emm*75-ST49 prevalent until 2018.
- In 2019, resistance surged to 9% driven by the expansion of *mef*(A)-*msr*(D)-positive *emm*2-ST55 isolates.
- Tetracycline resistance genes (*tet*(M), *tet*(O)) were often co-located with macrolide resistance genes (*erm*).
Conclusions:
- Clonal replacement events significantly influence macrolide resistance trends in pharyngeal GAS.
- Resistant GAS lineages exhibit distinct seasonal and clonal dynamics compared to susceptible strains.
- The findings highlight the need for continuous molecular surveillance of non-invasive GAS to track evolving resistance patterns.
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