Historic methicillin-resistant Staphylococcus aureus: expanding current knowledge using molecular epidemiological characterization of a Swiss legacy collection

Vanni Benvenga; Aline Cuénod; Srinithi Purushothaman; Gottfried Dasen; Maja Weisser; Stefano Bassetti; Tim Roloff; Martin Siegemund; Ulrich Heininger; Julia Bielicki; Marianne Wehrli; Paul Friderich; Reno Frei; Andreas Widmer; Kathrin Herzog; Hans Fankhauser; Oliver Nolte; Thomas Bodmer; Martin Risch; Olivier Dubuis; Sigrid Pranghofer; Romana Calligaris-Maibach; Susanne Graf; Vincent Perreten; Helena M B Seth-Smith; Adrian Egli

doi:10.1186/s13073-024-01292-w

Historic methicillin-resistant Staphylococcus aureus: expanding current knowledge using molecular epidemiological characterization of a Swiss legacy collection

Genome Med. 2024 Feb 5;16(1):23. doi: 10.1186/s13073-024-01292-w.

Authors

Vanni Benvenga^{1

2}, Aline Cuénod^{1

2}, Srinithi Purushothaman^{1

2}, Gottfried Dasen³, Maja Weisser⁴, Stefano Bassetti⁵, Tim Roloff^{1

2

6

7}, Martin Siegemund⁸, Ulrich Heininger⁹, Julia Bielicki⁹, Marianne Wehrli¹⁰, Paul Friderich¹¹, Reno Frei⁷, Andreas Widmer⁴, Kathrin Herzog¹², Hans Fankhauser¹³, Oliver Nolte^{2

14}, Thomas Bodmer¹⁵, Martin Risch¹⁵, Olivier Dubuis¹⁶, Sigrid Pranghofer¹⁷, Romana Calligaris-Maibach¹⁸, Susanne Graf¹⁹, Vincent Perreten^{20

21}, Helena M B Seth-Smith^{1

2

6

7}, Adrian Egli^{22

23

24

25}

Affiliations

¹ Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland.
² Institute of Medical Microbiology, University of Zurich, Gloriastrasse 28/30, Zurich, 8006, Switzerland.
³ Culture Collection of Switzerland, Wädenswil, Switzerland.
⁴ Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
⁵ Internal Medicine, University Hospital Basel, Basel, Switzerland.
⁶ Swiss Institute of Bioinformatics, University of Basel, Lausanne, Switzerland.
⁷ Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland.
⁸ Intensive Care Medicine, University Hospital Basel, Basel, Switzerland.
⁹ Infectious Diseases and Hospital Epidemiology, University of Basel Children's Hospital, Basel, Switzerland.
¹⁰ Microbiology Department, Hospital of Schaffhausen, Schaffhausen, Switzerland.
¹¹ Medicinal microbiology department, Hospital of Lucerne, Lucerne, Switzerland.
¹² Clinical Microbiology, Cantonal Hospital Thurgau, Münsterlingen, Switzerland.
¹³ Clinical Microbiology, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁴ Clinical Microbiology, Zentrum für Labormedizin St, Gallen, St. Gallen, Switzerland.
¹⁵ Labor Risch, Buchs, Liechtenstein.
¹⁶ Clinical Microbiology, Viollier AG, Allschwil, Switzerland.
¹⁷ Bioanalytica AG, Lucerne, Switzerland.
¹⁸ Clinical Microbiology, Cantonal Hospital Baden, Baden, Switzerland.
¹⁹ Clinical Microbiology, Cantonal Hospital Basellandschaft, Liestal, Switzerland.
²⁰ Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland.
²¹ Swiss Pathogen Surveillance Platform (SPSP), Lausanne, Switzerland.
²² Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland. aegli@imm.uzh.ch.
²³ Institute of Medical Microbiology, University of Zurich, Gloriastrasse 28/30, Zurich, 8006, Switzerland. aegli@imm.uzh.ch.
²⁴ Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland. aegli@imm.uzh.ch.
²⁵ Swiss Pathogen Surveillance Platform (SPSP), Lausanne, Switzerland. aegli@imm.uzh.ch.

Abstract

Background: Few methicillin-resistant Staphylococcus aureus (MRSA) from the early years of its global emergence have been sequenced. Knowledge about evolutionary factors promoting the success of specific MRSA multi-locus sequence types (MLSTs) remains scarce. We aimed to characterize a legacy MRSA collection isolated from 1965 to 1987 and compare it against publicly available international and local genomes.

Methods: We accessed 451 historic (1965-1987) MRSA isolates stored in the Culture Collection of Switzerland, mostly collected from the Zurich region. We determined phenotypic antimicrobial resistance (AMR) and performed whole genome sequencing (WGS) using Illumina short-read sequencing on all isolates and long-read sequencing on a selection with Oxford Nanopore Technology. For context, we included 103 publicly available international assemblies from 1960 to 1992 and sequenced 1207 modern Swiss MRSA isolates from 2007 to 2022. We analyzed the core genome (cg)MLST and predicted SCCmec cassette types, AMR, and virulence genes.

Results: Among the 451 historic Swiss MRSA isolates, we found 17 sequence types (STs) of which 11 have been previously described. Two STs were novel combinations of known loci and six isolates carried previously unsubmitted MLST alleles, representing five new STs (ST7843, ST7844, ST7837, ST7839, and ST7842). Most isolates (83% 376/451) represented ST247-MRSA-I isolated in the 1960s, followed by ST7844 (6% 25/451), a novel single locus variant (SLV) of ST239. Analysis by cgMLST indicated that isolates belonging to ST7844-MRSA-III cluster within the diversity of ST239-MRSA-III. Early MRSA were predominantly from clonal complex (CC)8. From 1980 to the end of the twentieth century, we observed that CC22 and CC5 as well as CC8 were present, both locally and internationally.

Conclusions: The combined analysis of 1761 historic and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss-German and international MRSA across time.

Keywords: Antimicrobial resistance; Historic; MLST; MRSA; Phylogeny; Switzerland; WGS.

MeSH terms

Anti-Bacterial Agents / pharmacology
Humans
Methicillin-Resistant Staphylococcus aureus* / genetics
Molecular Epidemiology
Multilocus Sequence Typing
Staphylococcal Infections* / epidemiology
Switzerland

Substances

Anti-Bacterial Agents