Identification and Characterization of the Multidrug Resistance Gene cfr in a Panton-Valentine Leukocidin-Positive Sequence Type 8 Methicillin-Resistant Staphylococcus aureus IVa (USA300) Isolate

Abstract

The staphylococcal cfr gene mediates resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A, a phenotype that has been termed PhLOPS A . The cfr gene has mainly been associated with coagulase-negative staphylococcal isolates from animals, and only a few cfr-positive methicillin-resistant Staphylococcus aureus (MRSA) isolates have been described so far. This study reports the first description of a cfr-positive MRSA isolate (M05/0060) belonging to the pandemic Panton-Valentine leukocidin (PVL)-positive sequence type 8 MRSA IVa/USA300 (ST8-MRSA-IVa/USA300) clone. The cfr gene was detected in M05/0060 using a DNA microarray which was used to screen PVL-positive MRSA isolates for the presence of virulence genes, typing markers, and antimicrobial resistance genes. Antimicrobial susceptibility testing revealed that M05/0060 exhibited the cfr-associated resistance phenotype. Molecular analysis identified the presence of cfr and a second phenicol resistance gene, fexA, on a novel 45-kb conjugative plasmid, which was designated pSCFS7. Within pSCFS7, a DNA segment consisting of cfr, a truncated copy of insertion sequence IS21-558, and a region with homology to the DNA invertase gene bin3 of transposon Tn552 from Bacillus mycoides was integrated into the transposase gene tnpB of the fexA-carrying transposon Tn558. The emergence of a multidrug-resistant cfr-positive variant of ST8-MRSA-IVa/USA300 is alarming and requires ongoing surveillance. Moreover, the identification of a novel conjugative plasmid carrying the cfr gene indicates the ability of cfr to spread to other MRSA strains.

Panton-Valentine Leukocidin-Positive Staphylococcus aureus in Ireland from 2002 to 2011: 21 Clones, Frequent Importation of Clones, Temporal Shifts of Predominant Methicillin-Resistant S. aureus Clones, and Increasing Multiresistance

“…Slightly Ͻ10% of the CC/ST8-MRSA-IV isolates were tetracycline resistant and carried tet(K). One isolate carried cfr and fexA and exhibited chloramphenicol and linezolid resistances (42 The number of isolates (n) represented by each spa type or IEC type are indicated in parentheses only when more than one spa or IEC type was identified within a genotype.…”

First Report of the Multidrug Resistance Gene cfr in Enterococcus faecalis of Animal Origin

“…In most reports, the cfr gene was located on different plasmids (9,10,16), while in a few cases, it was also detected in the chromosomal DNA (9,14,27). Recently, the first outbreak case of linezolid-resistant, cfr-carrying Staphylococcus aureus was reported in Spain (17), and the cfr gene has also been identified in Panton-Valentine leukocidin-positive sequence type 8 (ST8) methicillin-resistant S. aureus IVa (USA300) (23). These observations underline the increasing threat of this resistance determinant to public health.…”

Emergence of Hospital- and Community-Associated Panton-Valentine Leukocidin-Positive Methicillin-Resistant Staphylococcus aureus Genotype ST772-MRSA-V in Ireland and Detailed Investigation of an ST772-MRSA-V Cluster in a Neonatal Intensive Care Unit

“…Since 2002, isolates belonging to ST22-MRSA-IV have predominated as the cause of nosocomial infections (33,37,38). Several genotypes of PVL-positive CA-MRSA have also been reported in Ireland and have been linked to the importation of different strains, with ST30-MRSA-IV and ST8-MRSA-IV predominating (33).…”