A Look into the Melting Pot: The mecC-Harboring Region Is a Recombination Hot Spot in Staphylococcus stepanovicii

Introduction Horizontal gene transfer (HGT) is an important driver for resistance- and virulence factor accumulation in pathogenic bacteria such as Staphylococcus aureus. Methods Here, we have investigated the downstream region of the bacterial chromosomal attachment site (attB) for the staphylococcal cassette chromosome mec (SCCmec) element of a commensal mecC-positive Staphylococcus stepanovicii strain (IMT28705; ODD4) with respect to genetic composition and indications of HGT. S. stepanovicii IMT28705 was isolated from a fecal sample of a trapped wild bank vole (Myodes glareolus) during a screening study (National Network on “Rodent-Borne Pathogens”) in Germany. Whole genome sequencing (WGS) of IMT28705 together with the mecC-negative type strain CM7717 was conducted in order to comparatively investigate the genomic region downstream of attB (GenBank accession no. KR732654 and KR732653). Results The bank vole isolate (IMT28705) harbors a mecC gene which shares 99.2% nucleotide (and 98.5% amino acid) sequence identity with mecC of MRSA_LGA251. In addition, the mecC-encoding region harbors the typical blaZ-mecC-mecR1-mecI structure, corresponding with the class E mec complex. While the sequences downstream of attB in both S. stepanovicii isolates (IMT28705 and CM7717) are partitioned by 15 bp direct repeats, further comparison revealed a remarkable low concordance of gene content, indicating a chromosomal “hot spot” for foreign DNA integration and exchange. Conclusion Our data highlight the necessity for further research on transmission routes of resistance encoding factors from the environmental and wildlife resistome.

[1]  K. Becker,et al.  Methicillin resistance in Staphylococcus isolates: the "mec alphabet" with specific consideration of mecC, a mec homolog associated with zoonotic S. aureus lineages. , 2014, International journal of medical microbiology : IJMM.

[2]  F. Ruiz-Fons,et al.  Detection of methicillin-resistant Staphylococcus aureus (MRSA) carrying the mecC gene in wild small mammals in Spain. , 2014, The Journal of antimicrobial chemotherapy.

[3]  J. V. van Dijl,et al.  The Staphylococcal Cassette Chromosome mec type V from Staphylococcus aureus ST398 is packaged into bacteriophage capsids. , 2014, International journal of medical microbiology : IJMM.

[4]  S. Schwarz,et al.  Detection of a new mecC allotype, mecC2, in methicillin-resistant Staphylococcus saprophyticus. , 2014, The Journal of antimicrobial chemotherapy.

[5]  Daniel J. Wilson,et al.  Mobile elements drive recombination hotspots in the core genome of Staphylococcus aureus , 2014, Nature Communications.

[6]  J. Jacob,et al.  [Monitoring populations of rodent reservoirs of zoonotic diseases. Projects, aims and results]. , 2014, Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz.

[7]  J. Jacob,et al.  Monitoring von gesundheitsgefährdenden Nagetieren , 2014, Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz.

[8]  G. Arakere,et al.  Novel Rearrangements in the Staphylococcal Cassette Chromosome Mec Type V Elements of Indian ST772 and ST672 Methicillin Resistant Staphylococcus aureus Strains , 2014, PloS one.

[9]  J. Parkhill,et al.  A novel hybrid SCCmec-mecC region in Staphylococcus sciuri , 2013, The Journal of antimicrobial chemotherapy.

[10]  Fangfang Xia,et al.  The SEED and the Rapid Annotation of microbial genomes using Subsystems Technology (RAST) , 2013, Nucleic Acids Res..

[11]  C. Walzer,et al.  Characterization of methicillin-resistant Staphylococcus spp. carrying the mecC gene, isolated from wildlife. , 2013, The Journal of antimicrobial chemotherapy.

[12]  F. Tenover,et al.  Transduction of Staphylococcal Cassette Chromosome mec Elements between Strains of Staphylococcus aureus , 2013, Antimicrobial Agents and Chemotherapy.

[13]  D. Coleman,et al.  Staphylococcal cassette chromosome mec: recent advances and new insights. , 2013, International journal of medical microbiology : IJMM.

[14]  T. Baba,et al.  Genomic Basis for Methicillin Resistance in Staphylococcus aureus , 2013, Infection & chemotherapy.

[15]  V. Perreten,et al.  Genetic characterization of antimicrobial resistance in coagulase-negative staphylococci from bovine mastitis milk. , 2013, Journal of dairy science.

[16]  J. Parkhill,et al.  A Staphylococcus xylosus Isolate with a New mecC Allotype , 2012, Antimicrobial Agents and Chemotherapy.

[17]  L. Wieler,et al.  MRSA Variant in Companion Animals , 2012, Emerging infectious diseases.

[18]  J. Parkhill,et al.  The newly described mecA homologue, mecALGA251, is present in methicillin-resistant Staphylococcus aureus isolates from a diverse range of host species. , 2012, The Journal of antimicrobial chemotherapy.

[19]  G. Archer,et al.  Characterization of the Staphylococcus aureus rRNA Methyltransferase Encoded by orfX, the Gene Containing the Staphylococcal Chromosome Cassette mec (SCCmec) Insertion Site* , 2012, The Journal of Biological Chemistry.

[20]  A. Tomasz,et al.  Guidelines for Reporting Novel mecA Gene Homologues , 2012, Antimicrobial Agents and Chemotherapy.

[21]  P. Arede,et al.  The Anti-Repressor MecR2 Promotes the Proteolysis of the mecA Repressor and Enables Optimal Expression of β-lactam Resistance in MRSA , 2012, PLoS pathogens.

[22]  M. F. White,et al.  Staphylococcus aureus DinG, a helicase that has evolved into a nuclease , 2011, The Biochemical journal.

[23]  Antina Lübke-Becker,et al.  Methicillin-resistant staphylococci (MRS) and extended-spectrum beta-lactamases (ESBL)-producing Enterobacteriaceae in companion animals: nosocomial infections as one reason for the rising prevalence of these potential zoonotic pathogens in clinical samples. , 2011, International journal of medical microbiology : IJMM.

[24]  G. Archer,et al.  Characterization of DNA Sequences Required for the CcrAB-Mediated Integration of Staphylococcal Cassette Chromosome mec, a Staphylococcus aureus Genomic Island , 2011, Journal of bacteriology.

[25]  W. Witte,et al.  Rare Occurrence of Methicillin-Resistant Staphylococcus aureus CC130 with a Novel mecA Homologue in Humans in Germany , 2011, PloS one.

[26]  Julian Parkhill,et al.  Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study , 2011, The Lancet. Infectious diseases.

[27]  S. Monecke,et al.  Detection of Staphylococcal Cassette Chromosome mec Type XI Carrying Highly Divergent mecA, mecI, mecR1, blaZ, and ccr Genes in Human Clinical Isolates of Clonal Complex 130 Methicillin-Resistant Staphylococcus aureus , 2011, Antimicrobial Agents and Chemotherapy.

[28]  P. Masiewicz,et al.  Species distribution of staphylococci from small wild mammals. , 2010, Systematic and applied microbiology.

[29]  K. Hiramatsu,et al.  Origin and Molecular Evolution of the Determinant of Methicillin Resistance in Staphylococci , 2010, Antimicrobial Agents and Chemotherapy.

[30]  S. Schwarz,et al.  Identification and characterization of methicillin-resistant coagulase-negative staphylococci from bovine mastitis. , 2010, The Journal of antimicrobial chemotherapy.

[31]  J. Zakrzewska‐Czerwińska,et al.  Staphylococcus stepanovicii sp. nov., a novel novobiocin-resistant oxidase-positive staphylococcal species isolated from wild small mammals. , 2010, Systematic and applied microbiology.

[32]  Miriam L. Land,et al.  Trace: Tennessee Research and Creative Exchange Prodigal: Prokaryotic Gene Recognition and Translation Initiation Site Identification Recommended Citation Prodigal: Prokaryotic Gene Recognition and Translation Initiation Site Identification , 2022 .

[33]  T. Baba,et al.  Staphylococcal Cassette Chromosome mec-Like Element in Macrococcus caseolyticus , 2010, Antimicrobial Agents and Chemotherapy.

[34]  J. Weese,et al.  Coagulase positive staphylococcal colonization of humans and their household pets. , 2009, The Canadian veterinary journal = La revue veterinaire canadienne.

[35]  K. Ko,et al.  Classification of Staphylococcal Cassette Chromosome mec (SCCmec): Guidelines for Reporting Novel SCCmec Elements , 2009, Antimicrobial Agents and Chemotherapy.

[36]  M. Groschup,et al.  Network “Rodent-borne pathogens” in Germany: longitudinal studies on the geographical distribution and prevalence of hantavirus infections , 2008, Parasitology Research.

[37]  G. Archer,et al.  Gene Acquisition at the Insertion Site for SCCmec, the Genomic Island Conferring Methicillin Resistance in Staphylococcus aureus , 2007, Journal of bacteriology.

[38]  S. Stepanović,et al.  Evaluation of Phenotypic and Molecular Methods for Detection of Oxacillin Resistance in Members of the Staphylococcus sciuri Group , 2006, Journal of Clinical Microbiology.

[39]  A. Hanssen,et al.  SCCmec in staphylococci: genes on the move. , 2006, FEMS immunology and medical microbiology.

[40]  A. Friedrich,et al.  Different Clonal Complexes of Methicillin-Resistant Staphylococcus aureus Are Disseminated in the Euregio Meuse-Rhine Region , 2005, Antimicrobial Agents and Chemotherapy.

[41]  Xiao Xue Ma,et al.  Novel Type V Staphylococcal Cassette Chromosome mec Driven by a Novel Cassette Chromosome Recombinase, ccrC , 2004, Antimicrobial Agents and Chemotherapy.

[42]  Xiao Xue Ma,et al.  Insights on antibiotic resistance of Staphylococcus aureus from its whole genome: genomic island SCC. , 2003, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[43]  A. Tomasz,et al.  Development of Methicillin Resistance in Clinical Isolates of Staphylococcus sciuri by Transcriptional Activation of the mecA Homologue Native to the Species , 2003 .

[44]  A. Tomasz,et al.  An acquired and a native penicillin-binding protein cooperate in building the cell wall of drug-resistant staphylococci , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Teruyo Ito,et al.  Genetic Organization of the Chromosome Region Surrounding mecA in Clinical Staphylococcal Strains: Role of IS431-Mediated mecI Deletion in Expression of Resistance in mecA-Carrying, Low-Level Methicillin- Resistant Staphylococcus haemolyticus , 2001, Antimicrobial Agents and Chemotherapy.

[46]  M. Holmes,et al.  Phenotypic detection of mecC-MRSA: cefoxitin is more reliable than oxacillin. , 2014, The Journal of antimicrobial chemotherapy.

[47]  Clinical,et al.  Performance standards for antimicrobial disk and dilution susceptibilty tests for bacteria isolated from animals : approved standard , 2008 .