Characterization of SCCmec Instability in Methicillin-Resistant Staphylococcus aureus Affecting Adjacent Chromosomal Regions, Including the Gene for Staphylococcal Protein A (spa)

Author(s)

Isabella A. Tickler, Cepheid
Fred C. Tenover, CepheidFollow
C. R. Scharn, Creighton University
R. V. Goering, Creighton University

Document Type

Article

Publication Date

3-7-2022

Publication Source

Antimicrobial Agents and Chemotherapy

Abstract

Staphylococcal cassette chromosome mec (SCCmec) represents a sequence of clear clinical and diagnostic importance in staphylococci. At a minimum the chromosomal cassette contains the mecA gene encoding PBP2a but frequently also includes additional antibiotic resistance genes (e.g., ermA and aadC; macrolide and aminoglycoside resistance, respectively). Certain regions within SCCmec elements are hot spots for sequence instability due to cassette-specific recombinases and a variety of internal mobile elements. SCCmec changes may affect not only cassette stability but the integrity of adjacent chromosomal sequences (e.g., the staphylococcal protein A gene; spa). We investigated SCCmec stability in methicillin-resistant Staphylococcus aureus (MRSA) strains carrying one of four SCCmec types cultured in the absence of antimicrobial selection over a 3-month period. SCCmec rearrangements were first detected in cefoxitin-susceptible variants after 2 months of passage, and most commonly showed precise excision of the SCCmec element. Sequence analysis after 3 months revealed both precise SCCmec excision and a variety of SCCmec internal deletions, some including extensive adjacent chromosomal loss, including spa. No empty cassettes (i.e., loss of just mecA from SCCmec) were observed among the variants. SCCmec stability was influenced both by internal mobile elements (IS431) as well as the host cell environment. Genotypically similar clinical isolates with deletions in the spa gene were also included for purposes of comparison. The results indicate a role for host-cell influence and the IS431 element on SCCmec stability.

ISBN/ISSN

Print ISSN: 0066-4804; Online ISSN: 1098-6596

Document Version

Published Version

Comments

This document is made available for download in compliance with the publisher’s open-access policy. Permission documentation is on file.

Publisher

American Society for Microbiology

Volume

66

Peer Reviewed

yes

Issue

4

Keywords

MRSA, SCCmec, molecular typing, molecular diagnostics

Sponsoring Agency

F.C.T. and I.A.T. are employees of Cepheid, and R.V.G has received research funding from Cepheid. Funding for this study was provided internally by Creighton University.

eCommons Citation

Tickler, Isabella A.; Tenover, Fred C.; Scharn, C. R.; and Goering, R. V., "Characterization of SCCmec Instability in Methicillin-Resistant Staphylococcus aureus Affecting Adjacent Chromosomal Regions, Including the Gene for Staphylococcal Protein A (spa)" (2022). Biology Faculty Publications. 356.
https://ecommons.udayton.edu/bio_fac_pub/356