In the USA, dissemination of a major clone of community-associated methicillin-resistant S. aureus (CA-MRSA) designated USA300 and outbreaks of vancomycin-resistant Enterococcus faecalis (VREfs) have been described1,2. CA-MRSA infections emerged in Colombia in 20053 and 15 CA-MRSA infections were documented in four cities in 2006 to 2007, all of which presented with severe skin and soft tissue infections complicated by necrotizing fasciitis, bacteremia, paraspinal abscess, arthritis and meningitis with a mortality rate of 20%. The first known Colombian VREfs isolate was recovered in a hospital in Bogotá, 2001. Since then, 50 additional isolates have been identified in the following 6 years from different patients in seven hospitals in the same city.
The Colombian MRSA isolates were susceptible to most of anti-staphylococcal antibiotics (although 40% were tetracycline-resistant). All isolates harbored SCCmec type IV, the PVL genes, at least one of the toxins associated with USA3004 but lacked arcA. PFGE and multi-locus-sequence-typing (MLST) revealed that all but one clinical isolate were ST8 and clonally related to USA300. The remaining isolate was a single locus variant of ST8 (ST923) (Fig. 1, panel A). The majority of isolates carried SCCmec subtypes other than IVa which suggests that a similar lineage of virulent, ST8 methicillin-susceptible S. aureus that independently acquired various SCCmec subtypes existed in both Colombia and the USA. To our knowledge, this is the first documentation of the establishment of the USA300 CA-MRSA lineage as the predominant (and exclusive) clone in a country other than the USA. No CA-MRSA isolates belonging to a different (MLST) clonal cluster have been documented in Colombia so far.
Figure 1.
Panel A, Pulsed field gel electrophoresis (PFGE) (SmaI), origin, toxin profile, presence of arcA as a marker of the ACME (arginine catabolic mobile element) island and MLST of representative isolates of CA-MRSA from Colombia and the USA. SCCmec, staphylococcal chromosomal cassette mec; ST, sequence type; ND, not done. aUSA300-0114 strain, SCCmec IVa; bUSA300 strain carrying the SCCmec IVb; cthe presence of arcA has been associated with USA300 isolates carrying the SCCmec type IVa cassette but not others, consistent with the fact that ST-8 Colombian CA-MRSA may have acquired the SCCmec DNA independently from the US isolates; dSingle nucleotide variant (SNV) of ST8 in the yqiL gene. Panel B, PFGE electrophoresis using ApaI enzyme of representative isolates of vancomycin-resistant Enterococcus faecalis (VREfs) ST2 from seven hospitals in Bogotá, DC, Colombia from 2001 to 2006 and isolate TX2486, the index isolate of strain HV1 (ST2) recovered from a Houston hospital in 1994. Lane 1, TX2486; lane 2 and 3, ERV-25 and ERV-31 which are representatives of the first Colombian VREfs isolates recovered in 2001. VREfs isolates from 2002 and 2003 had an identical PFGE pattern to that of isolate ERV-31 and are not shown in the figure. Lane 4, 5 and 6, isolates ERV-62, ERV-63 and ERV-65 recovered in 2004; lane 7, ERV-81 isolated in 2005; lane 8, ERV-116, recovered in 2006.
PFGE also indicated that a single clone of VanB-VREfs has disseminated in Bogota, Colombia (Fig. 1, panel B). This clone is genetically related to an MLST ST2 outbreak strain (HV1) of VREfs described in Houston in 19945. Additionally, the allelic profile of the antigenic or resistance genes, ace, salA, and lsa (encoding an adhesin, a cell-wall antigen, and quinupristin-dalfopristin resistance, respectively) was also identical in both. Furthermore, both the Houston and Colombian isolates have the same pathogenicity island profile which has been suggested as an epidemiological marker of more virulent clones of E. faecalis5. To our knowledge, the only two epidemic strains of ST2 VanB-type E. faecalis described in the world are the Houston and Bogotá strains.
Our findings suggest that a close epidemiologic relationship has been established between Colombia and the USA in these two pathogenic and resistant species.
ACKNOWLEDGEMENTS
We are grateful to Jinnethe Reyes, Lorena Díaz, Diana Panesso, German A. Contreras, Shreedhar R. Nallapareddy and Kavindra V. Singh for technical assistance and useful discussions. We thank Carlos Alvarez for providing isolate Col-177, Kristina Hulten, Texas Children Hospital, for the gift of strain USA300-0114 and RV. Goering for providing MRSA USA300 carrying the SCCmec IVb strain. NARSA 123 was obtained from the Network on Antimicrobial Resistance in Staphylococcus aureus. We are indebted to Pablo Okhuysen and the Center for Clinical and Translational Research, University of Texas Health Science Center at Houston for technical assistance (National Institutes of Health grant UL1RR024148). This study was supported in part by grant NIH R37 AI47923 from the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID) to B.E.M. C.A.A is supported by a K99/R00 Pathway to Independence Award (1K99 AI72961) from NIAID.
Footnotes
DISCLOSURE STATEMENT
Dr. Arias has received lecture fees and grant support from Pfizer and Merck. Dr. Murray has grant support from Johnson & Johnson, Astellas and Intercell and has served as consultant for Astellas, Theravance, Cubist, Targanta, Johnson & Johnson and Pfizer. Dr. Coronell reports to be part of the speaker bureau of Wyeth pharmaceuticals, GlaxoSmithKline, Merck, and Abbot. Dr. Martinez has participated in local and regional advisory boards for Merck-Sharp and Dohme, Wyeth Pharmaceuticals, Janssen Laboratories, Pfizer and GlaxoSmithKline, and received research grants from Wyeth Pharmaceuticals
Contributor Information
Cesar A. Arias, Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogotá, Colombia and Division of Infectious Diseases, University of Texas Medical School at Houston, Houston, TX
Sandra Rincón, Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogotá, Colombia
Shahreen Chowdhury, Division of Infectious Diseases, University of Texas Medical School at Houston, Houston, TX..
Ernesto Martínez, Hospital Universitario del Valle, Cali, Colombia
Wilfrido Coronell, Hospital Bocagrande S.A and Department of Bacteriology and Microbiology, Universidad de Cartagena, Cartagena, Colombia.
Barbara E. Murray, Department of Internal Medicine, Division of Infectious Diseases, Center for the Study of Emerging and Reemerging Pathogens and Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston TX.
REFERENCES
- 1.Tenover FC, McDougal LK, Goering RV, Killgore G, Projan SJ, Patel JB, Dunman PM. Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States. J Clin Microbiol. 2006;44:108–118. doi: 10.1128/JCM.44.1.108-118.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Coque T, Coque TM, Tomayko JF, Ricke SC, Okhyusen PC, Murray BE. Vancomycin-resistant enterococci from nosocomial, community, and animal sources in the United States. Antimicrob Agents Chemother. 1996;40:2605–2609. doi: 10.1128/aac.40.11.2605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Alvarez CA, Barrientes OJ, Leal AL, et al. Community-associated methicillin-resistant Staphylococcus aureus, Colombia. Emerg Infect Dis. 2006;12:2000–2001. doi: 10.3201/eid1212.060814. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Diep BA, Gill SR, Chang RF, et al. Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet. 2006;367:731–739. doi: 10.1016/S0140-6736(06)68231-7. [DOI] [PubMed] [Google Scholar]
- 5.Nallapareddy SR, Wenxiang H, Weinstock GM, Murray BE. Molecular characterization of a widespread, pathogenic, and antibiotic resistance-receptive Enterococcus faecalis lineage and dissemination of its putative pathogenicity island. J Bacteriol. 2005;187:5709–5718. doi: 10.1128/JB.187.16.5709-5718.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]