Exploring the evolution and epidemiology of European CC1-MRSA-IV: tracking a multidrug-resistant community-associated meticillin-resistant Staphylococcus aureus clone

Abstract

This study investigated the evolution and epidemiology of the community-associated and multidrug-resistant Staphylococcus aureus clone European CC1-MRSA-IV. Whole-genome sequences were obtained for 194 European CC1-MRSA-IV isolates (189 of human and 5 of animal origin) from 12 countries, and 10 meticillin-susceptible precursors (from North-Eastern Romania; all of human origin) of the clone. Phylogenetic analysis was performed using a maximum-likelihood approach, a time-measured phylogeny was reconstructed using Bayesian analysis, and in silico microarray genotyping was performed to identify resistance, virulence-associated and SCCmec (staphylococcal cassette chromosome mec) genes. Isolates were typically sequence type 1 (190/204) and spa type t127 (183/204). Bayesian analysis indicated that European CC1-MRSA-IV emerged in approximately 1995 before undergoing rapid expansion in the late 1990s and 2000s, while spreading throughout Europe and into the Middle East. Phylogenetic analysis revealed an unstructured meticillin-resistant S. aureus (MRSA) population, lacking significant geographical or temporal clusters. The MRSA were genotypically multidrug-resistant, consistently encoded seh, and intermittently (34/194) encoded an undisrupted hlb gene with concomitant absence of the lysogenic phage-encoded genes sak and scn. All MRSA also harboured a characteristic ~5350 nt insertion in SCCmec adjacent to orfX. Detailed demographic data from Denmark showed that there, the clone is typically (25/35) found in the community, and often (10/35) among individuals with links to South-Eastern Europe. This study elucidated the evolution and epidemiology of European CC1-MRSA-IV, which emerged from a meticillin-susceptible lineage prevalent in North-Eastern Romania before disseminating rapidly throughout Europe.

Keywords: CA-MRSA; European CC1-MRSA-IV clone; epidemiology; evolution; phylogenomics; transmission.

Fig. 1.

A maximum-likelihood phylogeny based on 7066 SNPs. The red branches represent the European CC1-MRSA-IV clone, the blue branches represent CC1-MSSA precursors of European CC1-MRSA-IV and the black branches represent CC1 outgroup isolates. The countries and sites of isolate recovery are indicated in the key. The presence or absence of erm(C), tet(K) and sak/scn is indicated by the black or white circles, respectively. Isolate pairs or clusters containing isolates that differed by 10 or less SNPs are shaded in grey. The pink shapes on branch tips indicate that the isolate was recovered from an animal: circle, horse; rectangle, cat; triangle, wild rook. The majority of isolates were ST1 (MLST profile: 1-1-1-1-1-1-1) and spa type t127 (repeats succession: 07-23-21-16-34-33-13); non-ST1 and/or t127 variants are highlighted. One variant cluster (highlighted in turquoise) comprised one t7096 (14-13), one t398 (26-33-13) and four t174 (14-21-16-34-33-13) isolates. Four of these six isolates were also ST4110 (1-1-1-1-1-1-558). Another variant cluster (highlighted in green) comprised two German isolates, a Saudi Arabian isolate and a UAE isolate, all of which were spa type t386 (07-23-13). One of these isolates was also ST6001 (1-1-794-1-1-1-1). The remaining variants (highlighted in yellow) did not cluster into groups. Branches with 100 % bootstrap support are indicated with black dots. The tree scale denotes substitutions per site.

Fig. 2.

Bayesian analysis of 180 European CC1-MRSA-IV isolates and 10 MSSA precursors of the clone. (a) A Bayesian consensus tree based on 7330 non-recombinant core-genome SNPs and including 95 % HPD intervals across different dimensional partitioning of population sizes. (b) Posterior density distribution showing tree height (MRCA). (c) Estimated effective population size of the clone over time (dark line) including 95 % HPD intervals (grey shading) denoting uncertainty. (d) Posterior density distribution showing clock-rate estimates for the core-genome SNP alignment.