Complete nucleotide sequence of IS 431 mec in Staphylococcus aureus

The Cfr methyltransferase confers resistance to six classes of drugs which target the peptidyl transferase center of the 50S ribosomal subunit, including some oxazolidinones, such as linezolid ( L inezolid (LZD) resistance occurs predominantly through structural alterations to the oxazolidinone binding site in the 50S peptidyl transferase center (PTC) (1). These conformational changes are the result of mutations in genes encoding 23S rRNA (2, 3) or the ribosomal proteins L3 and L4 (4, 5) or via posttranscriptional modification of 23S rRNA base A2503 by the Cfr methyltransferase (6). Highly LZD r isolates that possess both the cfr gene and chromosomally encoded mutations have been identified (7-10).The horizontally transferrable, plasmid-borne nature of cfr makes this resistance determinant inherently more worrisome than chromosomally encoded resistance mechanisms that must arise independently and/or disseminate clonally (11,12). Adding to the potential for spread is the low fitness cost of this gene (13) and the broad spectrum of resistance conferred by Cfr to drugs included in the PhLOPS A phenotype (phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A class antibiotics) (6,12,14), as well as 16-member-ring macrolides (15). Within the oxazolidinone class, there are differences in susceptibilities of strains possessing cfr depending on structural features at both ends of the molecule. The addition of D-ring systems that pick up additional binding interactions in the PTC and the substitution of an A-ring C-5 hydroxymethyl group (in place of the bulkier acetamide-containing substituent found on LZD and other oxazolidinones) allow oxazolidinones such as tedizolid (TZD) (16) to retain greater potency than LZD in the presence of Cfr methylation (17).The cfr gene was first identified on the pSCFS1 plasmid in a Staphylococcus sciuri isolate recovered from a florfenicol-treated calf in Bavaria in 1997 (18). Since then, a variety of other veterinary staphylococci possessing cfr-bearing plasmids sharing similarity either to pSCFS1 or to one of two other groups possessing regions containing the cfr gene flanked by either IS256 or IS21-558 mobile elements have been identified (19). The first clinical cfrpositive strains reported were Staphylococcus aureus isolates recovered in 2005 from Ireland and Colombia. Irish methicillinresistant S. aureus (MRSA) isolate M05/0060 (no specific collection date given) (20) possessed the cfr-bearing pSCFS7 plasmid, which has similarity to the IS21-558-carrying veterinary plasmid pSCFS3 (21), although only a truncated portion of the IS21-558 element remained (22). Colombian MRSA isolate CM05 was recovered in May 2005 from a patient in Medellin, Colombia, who had briefly undergone LZD therapy (2 doses) (6, 23). The cfr gene in CM05 was chromosomally located and shared flanking sequence with high similarity to the pSM19035 Gram-positive multidrug resistance plasmid, including an IS21-558 element (24,25). Subsequently, additional cfr-positive clinical staphylococci and ente...

Section: Resultsmentioning

confidence: 99%

Linezolid-Resistant Staphylococcus aureus Strain 1128105, the First Known Clinical Isolate Possessing thecfrMultidrug Resistance Gene

Locke

Zuill

Scharn

et al. 2014

“…IS257.3-IS257.4 except for one residue (1,2,17). This similarity and our results for R155 with oligonucleotide probe T45B suggest that IS431mec, IS257.3-IS257.4, and IS2S7.3J-IS257.4J constitute a subfamily within the large IS257 family (17,23,24).…”

Section: Is2572 (17)mentioning

confidence: 99%

Physical mapping of the mec region of an American methicillin-resistant Staphylococcus aureus strain

Dubin

Matthews

Chikramane

et al. 1991

We mapped part of the mec region of a locally prevalent strain of Staphylococcus aureus. The mec region was found to harbor an insert of the transposon Tn554, which encodes spectinomycin and macrolide-lincosamide-streptogramin B resistance, and a 4.6-kb segment of DNA that contains the kanamycin resistance gene aadD. This 4.6-kb segment appears to be an integrated form of a previously described plasmid, pUB110, and is flanked by copies of the insertion sequence IS257. The integration event may be an example of processes that have led to accretion of resistance determinants in the mec region of S. aureus.

“…IS431, a well-known mobile genetic element in staphylococci, is 782 bp long (IS431mec) and contains an open reading frame (ORF) of a putative transposase gene and 14-to 22-bp terminal inverted repeats (3,4). IS431 is implicated in transfer of a gene(s) or entire plasmid into other replicons or the chromosome, and particularly in transfer of antimicrobial resistance genes, because variable resistance genes are found to be flanked by IS431 (18,19).…”

mentioning

confidence: 99%

Genomic Rearrangement of the mec Regulator Region Mediated by Insertion of IS 431 in Methicillin-Resistant Staphylococci

Kobayashi

Alam

Urasawa

2001

Genomic diversification of the mec regulator region mediated by IS431 was investigated for clinical isolates of methicillin-resistant staphylococci. A single rearranged form of the mecR1 gene due to IS431 insertion was detected in the three staphylococcal species, while another type of mecR1 truncation with IS431 and an IS431 located downstream of mecI were found only in Staphylococcus haemolyticus. Genetic differentiation of IS431 and staphylococcal isolates suggested transmission of mecDNA with IS431-mediated rearrangement among different staphylococcal species.