title: Resistance gene pool to co-trimoxazole in non-susceptible Nocardia strains.
abstract: The soil-borne pathogen Nocardia sp. causes severe cutaneous, pulmonary, and central nervous system infections. Against them, co-trimoxazole (SXT) constitutes the mainstay of antimicrobial therapy. However, some Nocardia strains show resistance to SXT, but the underlying genetic basis is unknown. We investigated the presence of genetic resistance determinants and class 1-3 integrons in 76 SXT-resistant Nocardia strains by PCR and sequencing. By E test, these clinical strains showed SXT minimum inhibitory concentrations of ≥32:608 mg/L (ratio of 1:19 for trimethoprim: sulfamethoxazole). They belonged to 12 species, being the main representatives Nocardia farcinica (32%), followed by N. flavorosea (6.5%), N. nova (11.8%), N. carnea (10.5%), N. transvalensis (10.5%), and Nocardia sp. (6.5%). The prevalence of resistance genes in the SXT-resistant strains was as follows: sul1 and sul2 93.4 and 78.9%, respectively, dfrA(S1) 14.7%, blaTEM-1 and blaZ 2.6 and 2.6%, respectively, VIM-2 1.3%, aph(3')-IIIa 40.8%, ermA, ermB, mefA, and msrD 2.6, 77.6, 14.4, and 5.2%, respectively, and tet(O), tet(M), and tet(L) 48.6, 25.0, and 3.9%, respectively. Detected amino acid changes in GyrA were not related to fluoroquinolone resistance, but probably linked to species polymorphism. Class 1 and 3 integrons were found in 93.42 and 56.57% strains, respectively. Class 2 integrons and sul3 genes were not detected. Other mechanisms, different than dfrA(S1), dfrD, dfrF, dfrG, and dfrK, could explain the strong trimethoprim resistance shown by the other 64 strains. For first time, resistance determinants commonly found in clinically important bacteria were detected in Nocardia sp. sul1, sul2, erm(B), and tet(O) were the most prevalent in the SXT-resistant strains. The similarity in their resistome could be due to a common genetic platform, in which these determinants are co-transferred.
authors.affiliation: Servicio de Bacteriología and Taxonomía, Centro Nacional de Microbiología, Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Valdezate
authors.affiliation: Servicio de Bacteriología and Taxonomía, Centro Nacional de Microbiología, Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Garrido
authors.affiliation: Servicio de Bacteriología and Taxonomía, Centro Nacional de Microbiología, Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Carrasco
authors.affiliation: Servicio de Bacteriología and Taxonomía, Centro Nacional de Microbiología, Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Villalón
authors.affiliation: Servicio de Bacteriología and Taxonomía, Centro Nacional de Microbiología, Instituto de Salud Carlos III Madrid, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Medina-Pascual
authors.affiliation: Servicio de Bacteriología and Taxonomía, Centro Nacional de Microbiología, Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Saéz-Nieto
keywords: Nocardia species; antimicrobial resistant determinants; co-trimoxazole; integrons