Origin and Evolution of European Community-Acquired Methicillin- Resistant Staphylococcus aureus

Marc Stegger; Thierry Wirth; Paal S. Andersen; Robert L. Skov; Anna De Grassi; Patricia Martins Simões; Anne Tristan; Andreas Petersen; Maliha Aziz; Kristoffer Kiil; Ivana Cirkovic; Edet E. Udo; Rosa del Campo; Jaana Vuopio-Varkila; Norazah Ahmad; Sima Tokajian; Georg Peters; Frieder Schaumburg; Barbro Olsson-Liljequist; Michael Givskov; Elizabeth E. Driebe; Henrik Erdman Vigh; Adebayo Shittu; Nadjia Ramdani-Bougessa; Jean-Philippe Rasigade; Lance B. Price; Francois Vandenesch; Anders R. Larsen; Frederic Laurent

doi:10.1128/mBio.01044-14

Origin and Evolution of European Community-Acquired Methicillin- Resistant Staphylococcus aureus

Marc Stegger, Thierry Wirth, Paal S. Andersen, Robert L. Skov, Anna De Grassi, Patricia Martins Simões, Anne Tristan, Andreas Petersen, Maliha Aziz, Kristoffer Kiil, Ivana Cirkovic, Edet E. Udo, Rosa del Campo, Jaana Vuopio-Varkila, Norazah Ahmad, Sima Tokajian, Georg Peters, Frieder Schaumburg, Barbro Olsson-Liljequist, Michael GivskovElizabeth E. Driebe, Henrik Erdman Vigh, Adebayo Shittu, Nadjia Ramdani-Bougessa, Jean-Philippe Rasigade, Lance B. Price, Francois Vandenesch, Anders R. Larsen, Frederic Laurent

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Abstract

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations.

IMPORTANCE: With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA.

Original language	English
Article number	e01044-14
Journal	mBio (Print)
Volume	5
Issue number	5
Pages (from-to)	1-12
Number of pages	12
ISSN	2161-2129
DOIs	https://doi.org/10.1128/mBio.01044-14
Publication status	Published - 26 Aug 2014

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Stegger, M., Wirth, T., Andersen, P. S., Skov, R. L., De Grassi, A., Martins Simões, P., Tristan, A., Petersen, A., Aziz, M., Kiil, K., Cirkovic, I., Udo, E. E., del Campo, R., Vuopio-Varkila, J., Ahmad, N., Tokajian, S., Peters, G., Schaumburg, F., Olsson-Liljequist, B., ... Laurent, F. (2014). Origin and Evolution of European Community-Acquired Methicillin- Resistant Staphylococcus aureus. mBio (Print), 5(5), 1-12. [e01044-14]. https://doi.org/10.1128/mBio.01044-14

Stegger, M, Wirth, T, Andersen, PS, Skov, RL, De Grassi, A, Martins Simões, P, Tristan, A, Petersen, A, Aziz, M, Kiil, K, Cirkovic, I, Udo, EE, del Campo, R, Vuopio-Varkila, J, Ahmad, N, Tokajian, S, Peters, G, Schaumburg, F, Olsson-Liljequist, B, Givskov, M, Driebe, EE, Vigh, HE, Shittu, A, Ramdani-Bougessa, N, Rasigade, J-P, Price, LB, Vandenesch, F, Larsen, AR & Laurent, F 2014, 'Origin and Evolution of European Community-Acquired Methicillin- Resistant Staphylococcus aureus', mBio (Print), vol. 5, no. 5, e01044-14, pp. 1-12. https://doi.org/10.1128/mBio.01044-14

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title = "Origin and Evolution of European Community-Acquired Methicillin- Resistant Staphylococcus aureus",

abstract = "Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations.IMPORTANCE: With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA.",

author = "Marc Stegger and Thierry Wirth and Andersen, {Paal S.} and Skov, {Robert L.} and {De Grassi}, Anna and {Martins Sim{\~o}es}, Patricia and Anne Tristan and Andreas Petersen and Maliha Aziz and Kristoffer Kiil and Ivana Cirkovic and Udo, {Edet E.} and {del Campo}, Rosa and Jaana Vuopio-Varkila and Norazah Ahmad and Sima Tokajian and Georg Peters and Frieder Schaumburg and Barbro Olsson-Liljequist and Michael Givskov and Driebe, {Elizabeth E.} and Vigh, {Henrik Erdman} and Adebayo Shittu and Nadjia Ramdani-Bougessa and Jean-Philippe Rasigade and Price, {Lance B.} and Francois Vandenesch and Larsen, {Anders R.} and Frederic Laurent",

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TY - JOUR

T1 - Origin and Evolution of European Community-Acquired Methicillin- Resistant Staphylococcus aureus

AU - Stegger, Marc

AU - Wirth, Thierry

AU - Andersen, Paal S.

AU - Skov, Robert L.

AU - De Grassi, Anna

AU - Martins Simões, Patricia

AU - Tristan, Anne

AU - Petersen, Andreas

AU - Aziz, Maliha

AU - Kiil, Kristoffer

AU - Cirkovic, Ivana

AU - Udo, Edet E.

AU - del Campo, Rosa

AU - Vuopio-Varkila, Jaana

AU - Ahmad, Norazah

AU - Tokajian, Sima

AU - Peters, Georg

AU - Schaumburg, Frieder

AU - Olsson-Liljequist, Barbro

AU - Givskov, Michael

AU - Driebe, Elizabeth E.

AU - Vigh, Henrik Erdman

AU - Shittu, Adebayo

AU - Ramdani-Bougessa, Nadjia

AU - Rasigade, Jean-Philippe

AU - Price, Lance B.

AU - Vandenesch, Francois

AU - Larsen, Anders R.

AU - Laurent, Frederic

N1 - Prinicple author Mark Stegger, Statens Serums iNstitut

PY - 2014/8/26

Y1 - 2014/8/26

N2 - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations.IMPORTANCE: With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA.

AB - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations.IMPORTANCE: With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA.

U2 - 10.1128/mBio.01044-14

DO - 10.1128/mBio.01044-14

M3 - Journal article

SN - 2161-2129

VL - 5

SP - 1

EP - 12

JO - mBio

JF - mBio

IS - 5

M1 - e01044-14

ER -

Origin and Evolution of European Community-Acquired Methicillin- Resistant Staphylococcus aureus

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