Methicillin Resistance Transfer from Staphylocccus epidermidis to Methicillin-Susceptible Staphylococcus aureus in a Patient during Antibiotic Therapy

Abstract

BackgroundThe mecA gene, encoding methicillin resistance in staphylococci, is located on a mobile genetic element called Staphylococcal Cassette Chromosome mec (SCCmec). Horizontal, interspecies transfer of this element could be an important factor in the dissemination of methicillin-resistant S. aureus (MRSA). Previously, we reported the isolation of a closely related methicillin-susceptible Staphylococcus aureus (MSSA), MRSA and potential SCCmec donor Staphylococcus epidermidis isolate from the same patient. Based on fingerprint techniques we hypothesized that the S. epidermidis had transferred SCCmec to the MSSA to become MRSA. The aim of this study was to show that these isolates form an isogenic pair and that interspecies horizontal SCCmec transfer occurred.Methodology/ResultsWhole genome sequencing of both isolates was performed and for the MSSA gaps were closed by conventional sequencing. The SCCmec of the S. epidermidis was also sequenced by conventional methods. The results show no difference in nucleotide sequence between the two isolates except for the presence of SCCmec in the MRSA. The SCCmec of the S. epidermidis and the MRSA are identical except for a single nucleotide in the ccrB gene, which results in a valine to alanine substitution. The main difference with the closely related EMRSA-16 is the presence of SaPI2 encoding toxic shock syndrome toxin and exfoliative toxin A in the MSSA-MRSA pair. No transfer of SCCmec from the S. epidermidis to the MSSA could be demonstrated in vitro.ConclusionThe MSSA and MRSA form an isogenic pair except for SCCmec. This strongly supports our hypothesis that the MRSA was derived from the MSSA by interspecies horizontal transfer of SCCmec from S. epidermidis O7.1.

Staphylococcal cassette chromosome mec typing and mecA sequencing in methicillin-resistant staphylococci from Algeria: a highly diversified element with new mutations in mecA

“…These findings, in accordance with other studies, confirm that S. haemolyticus can be considered as a reservoir of ccrC and a source for generating SCCmec VII (Ruppe et al, 2009;Urushibara et al, 2011;Bouchami et al, 2012). In a similar way, MR S. epidermidis appears to be a reservoir of ccrB and SCCmec IV (Ruppe et al, 2009;Barbier et al, 2010;Bloemendaal et al, 2010). With these observations, we suggest that the type of SCCmec is defined by species where it was generated.…”

“…This MGE is inserted at the attB site downstream of orfX, a conserved gene among all staphylococci and described recently as ribosomal methyltransferase of the RlmH type (Boundy et al, 2013). Various reports suggesting exchange of the SCCmec by horizontal transfer between different species of Staphylococcaceae have been published (Berglund & Söderquist, 2008;Bloemendaal et al, 2010). According to the recent report of the International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements (IWG-SCC) (www.sccmec.org), 11 types (I-XI) of SCCmec have been assigned for S. aureus, which are defined by a combination of mec gene complex class and cassette chromosome recombinase gene (ccr) allotype.…”

Antibiotic surgical prophylaxis increases nasal carriage of antibiotic-resistant staphylococci

“…With the increase in nasal carriage of antibiotic-resistant S. epidermidis the reservoir of antibiotic resistance genes that could potentially transfer into other species, S. aureus in particular, is increased. Horizontal transfer of meticillin resistance from S. epidermidis to S. aureus in a neonatal patient who received antibiotics has been reported (Wielders et al, 2001;Bloemendaal et al, 2010). CNS, including S. epidermidis, are the most common cause of prosthetic joint infections; as well as the skin, the nose is a potential source of postoperative infection (Tande & Patel, 2014).…”

Dissemination of Resistance and Virulence Determinants in Methicillin-Resistant Staphylococcus aureus During Colonization and Disease: A Review

“…Horizontal transfer of mobile genetic elements carrying resistance and virulence gene occurs at a higher frequency between strains of the same cluster while limited between strains of different clusters (Rapacka-Zdonczyk et al, 2014). In addition, successful in vivo horizontal transfer of mobile genetic elements carrying resistance and virulence determinants have contributed immensely to a global dissemination of virulent and multi-drug resistant pathogens (Bloemendaal et al, 2010;Corvaglia et al, 2010).…”