Genomic Stability of Composite SCCmec ACME and COMER-Like Genetic Elements in Staphylococcus epidermidis Correlates With Rate of Excision

Abstract

The epidemiological success of methicillin-resistant Staphylococcus aureus USA300 has been associated with the presence of two mobile elements, the arginine catabolic mobile element (ACME) and the copper and mercury resistance (COMER) element. These two mobile elements are associated with resistance to copper, which has been related to host fitness and survival within macrophages. Several studies found that ACME is more prevalent, and exhibits greater diversity, in Staphylococcus epidermidis while COMER has not been identified in S. epidermidis or any other staphylococcal species. We aimed in this study to evaluate the presence and diversity of ACME and COMER-like elements in our S. epidermidis clinical isolates. The genomes of 58 S. epidermidis clinical isolates, collected between 2009 and 2018 in a Scottish hospital, were sequenced. A core-genome phylogenetic tree and genome based MLST typing showed that more than half of the isolates belong to the clinically predominant sequence type2 (ST2) and these isolates have been found to split into two lineages within the phylogenetic tree. Analysis showed the presence of SCCmec in the majority of isolates. Comparative analysis identified a cluster of ACME-positive isolates with most of them belonging to ST48. ACME showed high variation even between isolates of the same ACME type and ST. COMER-like elements have been identified in one of the two major hospital adapted drug resistant ST2 lineages; and showed high stability. This difference in stability at the genomic level correlates well with the up to one hundred times higher excision frequency found for the SCCmec elements in ACME-containing isolates compared to COMER-like element containing isolates. ACME/COMER-like element positive isolates did not show a significant phenotype of decreased copper susceptibility, while resistance to mercury was over-represented in COMER-like element

The Effect of Iodine-Containing Nano-Micelles, FS-1, on Antibiotic Resistance, Gene Expression and Epigenetic Modifications in the Genome of Multidrug Resistant MRSA Strain Staphylococcus aureus ATCC BAA-39

“…A similar destabilization of the virulence plasmid in the FS-1 treated E. coli BAA-196 was reported in a previous publication (Korotetskiy et al, 2020b). The varying rate of excision of SCCmec cassettes from Staphylococcal populations was reported in another publication (Almebairik et al, 2020). However, it should be noted that in the current work, the rate of SCCmec excision in NC and FS cultures was not measured.…”

“…The staphylococcal methicillinresistance chromosome cassette (SCCmec), comprising mecA and mecR genes (Holden et al, 2004;Jani et al, 2017), was found in both genomes ∼50 kbp downstream from the replication origin. However, the coverage of PacBio reads overlapping the SCCmec region decreased significantly in both NC and FS genomes, indicating that this mobile element could be unstable in the culture and that there was a tendency to drop this element when S. aureus was cultivated without the selective pressure of the antibiotic that is in agreement with previously published reports (Stojanov et al, 2015;Almebairik et al, 2020). This may explain the fact that both NC and FS cultures gained sensitivity to methicillin after 10 passages of cultivation on the media without the antibiotic (Table 1).…”

“…Other authors suggested epistatic mechanisms of regulation of the level of antibiotic resistance and the associated fitness cost (Durão et al, 2018). The significant methicillin resistance reduction observed in the culture NC may be explained also by excision of staphylococcal methicillinresistance chromosome cassettes (SCCmec) from chromosomes that occurs naturally on the methicillin-free media with a rate from 10 −8 to 10 −5 depending on the tested strain and the presence of other genomic islands (Stojanov et al, 2015;Almebairik et al, 2020). Cultivation with 1/2 MBC FS-1 induced antibiotic resistance reversion in the treated bacterium compared to the initial strain and the variant NC.…”

Distinct clonal lineages and within-host diversification shape invasive Staphylococcus epidermidis populations

“…While in HD29 only an ACME type V-associated fragment containing the ars -operon and a putative functional CRISPR-Cas system was deleted in INF isolates. This shows that rearrangements occur relatively often in the region of SCC mec and ACME compared to other regions ( S10 Table ), as has been observed in vitro [ 55 – 57 ]. Interestingly, deletions in these regions seem to occur preferentially in infection, while integrity is maintained in the nose.…”

Whole Genome Sequencing of Methicillin-Resistant Staphylococcus epidermidis Clinical Isolates Reveals Variable Composite SCCmec ACME among Different STs in a Tertiary Care Hospital in Oman

“…These rearrangements indicate the high genomic plasticity of S. epidermidis particularly in the SCCmec and ACME region compared to other regions. This observation has also been noted in in vitro studies where ACME have highly variable structures with 100 times higher excision frequency found for the SCCmec elements [3,19].…”