Frequent occurrence of trimethoprim-sulfamethoxazole hetero-resistant Staphylococcus aureus isolates in different African countries.
High rates of trimethoprim/sulfamethoxazole (SXT) resistance, a combination of two antifolate antibiotics trimethoprim (TMP) and sulfamethoxazole (SMZ), have been reported among Staphylococcus aureus isolates in Portuguese-speaking African countries. Our study aimed to evaluate the occurrence of TMP resistance markers in major SXTRmethicillin-resistant S. aureus (MRSA) clones from these countries. We accessed also different fitness traits that could explain the success of these isolates over the Brazilian MRSA (the most successful SXTRMRSA clone worldwide but never identified in these countries). Minimum inhibitory concentrations for SXT, TMP and SMZ were determined, and genes encoding TMP resistance (dfrG, dfrA, dfrK and dfrB) were searched. Representatives of the Brazilian clone and of the major MRSA African clones were evaluated for their fitness by individual growth curves, competition assays, survival under desiccation, autolytic activity, resistance to oxidative stress, and also growth at high osmolarity and in acid and alkaline environments. Although all African isolates showed high-level resistance to TMP, the majority presented hetero-resistance to SXT. TMP resistance was linked to the presence of dfrG (78%), dfrA (19%) or both (3%) genes. Compared to the Brazilian clone, the African isolates showed higher growth rates and autolytic activity, and better survival to desiccation and alkaline conditions. Since isolates exhibiting SXT hetero-resistance are frequent in Africa, the implementation of standardized guidelines to detect this phenomenon is of major interest. The predominant MRSA clones in Portuguese-speaking African countries likely possess significant advantages over other clones, such as the Brazilian MRSA, that may explain their epidemiological success.
Laboratory of Molecular Genetics, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
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Coelho
Laboratory of Molecular Genetics, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.|Laboratory of Microbiology and Infectious Diseases, The Rockefeller University, New York, NY, USA.
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de Lencastre
Escola Superior de Saúde da Cruz Vermelha Portuguesa, Avenida de Ceuta, n°1, Edifício UrbiCeuta, 1300-125, Lisbon, Portugal. msousa@esscvp.eu.
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Aires-de-Sousa
D000349:Africa; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial; D056084:Genetic Fitness; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D015995:Prevalence; D013203:Staphylococcal Infections / Q000382:microbiology*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination