title: Emergence of trimethoprim resistance gene dfrG in Staphylococcus aureus causing human infection and colonization in sub-Saharan Africa and its import to Europe.
abstract: OBJECTIVE
  Co-trimoxazole (trimethoprim/sulfamethoxazole) is clinically valuable in treating skin and soft tissue infections (SSTIs) caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA). The genetic basis of emerging trimethoprim/sulfamethoxazole resistance in S. aureus from Africa is unknown. Such knowledge is essential to anticipate its further spread. We investigated the molecular epidemiology of trimethoprim resistance in S. aureus collected in and imported from Africa.
  
  
  METHODS
  Five hundred and ninety-eight human S. aureus isolates collected at five locations across sub-Saharan Africa [Gabon, Namibia, Nigeria (two) and Tanzania] and 47 isolates from travellers treated at six clinics in Europe because of SSTIs on return from Africa were tested for susceptibility to trimethoprim, sulfamethoxazole and trimethoprim/sulfamethoxazole, screened for genes mediating trimethoprim resistance in staphylococci [dfrA (dfrS1), dfrB, dfrG and dfrK] and assigned to spa genotypes and clonal complexes.
  
  
  RESULTS
  In 313 clinical and 285 colonizing S. aureus from Africa, 54% of isolates were resistant to trimethoprim, 21% to sulfamethoxazole and 19% to trimethoprim/sulfamethoxazole. We found that 94% of trimethoprim resistance was mediated by the dfrG gene. Of the 47 S. aureus isolates from travellers with SSTIs, 27 (57%) were trimethoprim resistant and carried dfrG. Markers of trimethoprim resistance other than dfrG were rare. The presence of dfrG genes in S. aureus was neither geographically nor clonally restricted.
  
  
  CONCLUSIONS
  dfrG, previously perceived to be an uncommon cause of trimethoprim resistance in human S. aureus, is widespread in Africa and abundant in imported S. aureus from ill returning travellers. These findings may foreshadow the loss of trimethoprim/sulfamethoxazole for the empirical treatment of SSTIs caused by community-associated MRSA.
authors.affiliation: Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Tropenmedizin, Universitätsklinikum, Wilhelmstraße 27, 72074 Tübingen, Germany Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum, Elfriede-Aulhorn-Straße 6, 72076 Tübingen, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Nurjadi
authors.affiliation: Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Tropenmedizin, Universitätsklinikum, Wilhelmstraße 27, 72074 Tübingen, Germany Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, PO Box 4000, Ogbomoso, Nigeria.
authors.forename: Adesola O
authors.initials: AO
authors.lastname: Olalekan
authors.affiliation: Nationales Referenzzentrum für Staphylokokken und Enterokokken, Robert Koch Institut, Burgstraße 37, 38855 Wernigerode, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Layer
authors.affiliation: Department of Microbiology, Obafemi Awolowo University, Ile-Ife 22005, Nigeria.
authors.forename: Adebayo O
authors.initials: AO
authors.lastname: Shittu
authors.affiliation: Centre de Recherches Médicales de Lambaréné (CERMEL), B.P. 118, Lambaréné, Gabon.
authors.forename: Abraham
authors.initials: A
authors.lastname: Alabi
authors.affiliation: Institut für Medizinische Mikrobiologie, Universitätsklinikum, Leipziger Straße 44, 39120 Magdeburg, Germany/Department Humanmedizin, Universität Witten/Herdecke, Alfred-Herrhausen-Straße 50, 58448 Witten, Germany/Helios Clinic, Heusnerstraße 40, 42283 Wuppertal, Germany.
authors.forename: Beniam
authors.initials: B
authors.lastname: Ghebremedhin
authors.affiliation: Institut für Medizinische Mikrobiologie, Universitätsklinikum Münster, Domagkstraße 10, 48149 Münster, Germany.
authors.forename: Frieder
authors.initials: F
authors.lastname: Schaumburg
authors.affiliation: Bagamoyo Research and Training Center, Ifakara Health Institute, PO Box 74, Bagamoyo, Tanzania Universitätsklinikum Freiburg, Abteilung Infektiologie, Hugstetter Straße 55, 79106 Freiburg, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hofmann-Eifler
authors.affiliation: Instituut voor Tropische Ziekten, Havenziekenhuis, Haringvliet 72, 3011 TG Rotterdam, The Netherlands.
authors.forename: Perry J J
authors.initials: PJ
authors.lastname: Van Genderen
authors.affiliation: Service de Maladies Infectieuses et Tropicales, groupe hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651 Paris cedex 13, France/Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Caumes
authors.affiliation: Tropenklinik, Paul-Lechler-Krankenhaus, 72076 Tübingen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Fleck
authors.affiliation: Institut für Tropenmedizin und Internationale Gesundheit, Charité-Universitätsmedizin Berlin, Spandauer Damm 130, 14050 Berlin, Germany.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum des Saarlandes, Kirrberger Straße, 66421 Homburg/Saar, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Universitätsklinikum Freiburg, Abteilung Infektiologie, Hugstetter Straße 55, 79106 Freiburg, Germany.
authors.forename: Winfried V
authors.initials: WV
authors.lastname: Kern
authors.affiliation: Bagamoyo Research and Training Center, Ifakara Health Institute, PO Box 74, Bagamoyo, Tanzania.
authors.forename: Salim
authors.initials: S
authors.lastname: Abdulla
authors.affiliation: Centre de Recherches Médicales de Lambaréné (CERMEL), B.P. 118, Lambaréné, Gabon Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 Amsterdam, The Netherlands.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.affiliation: Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Tropenmedizin, Universitätsklinikum, Wilhelmstraße 27, 72074 Tübingen, Germany Centre de Recherches Médicales de Lambaréné (CERMEL), B.P. 118, Lambaréné, Gabon.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.affiliation: Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum, Elfriede-Aulhorn-Straße 6, 72076 Tübingen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolz
authors.affiliation: Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Tropenmedizin, Universitätsklinikum, Wilhelmstraße 27, 72074 Tübingen, Germany philipp.zanger@uni-heidelberg.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Zanger
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D005060:Europe; D005798:Genes, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D058889:Molecular Typing; D018461:Soft Tissue Infections / Q000382:microbiology / Q000635:transmission; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000635:transmission*; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D014195:Travel; D014296:Trimethoprim Resistance
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial
keywords: communicable diseases; drug resistance; emerging; gene transfer; horizontal; infectious; methicillin-resistant Staphylococcus aureus; microbial; plasmids; public health surveillance; skin diseases; soft tissue infections; sulphonamides; tetrahydrofolate dehydrogenase; travel; trimethoprim/sulfamethoxazole combination