Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes

Abstract

Trimethoprim/sulfamethoxazole (TMP/SMX) resistance remains a serious threat in the treatment of Stenotrophomonas maltophilia infections. We analyzed an international collection of 55 S. maltophilia TMP/SMX-sensitive (S) (n=30) and -resistant (R) (n=25) strains for integrons; sul1, sul2 and dhfr genes; and insertion element common region (ISCR) elements. sul1, as part of a class 1 integron, was detected in 17 of 25 TMP/SMX-R. Nine TMP/SMX-R strains carried sul2; 7 were on large plasmids. Five TMP/SMX-R isolates were positive for ISCR2, and 4 were linked to sul2; 2 others possessed ISCR3. Two ISCR2s were adjacent to floR. Six TMP/SMX-S isolates harbored novel ISCR elements, ISCR9 and ISCR10. Linkage of ISCR3, ISCR9, and ISCR10 to sul2 and dhfr genes was not demonstrated. The data from this study indicate that class 1 integrons and ISCR elements linked to sul2 genes can mediate TMP/SMX resistance in S. maltophilia and are geographically widespread, findings that reinforce the need for ongoing resistance surveillance.

Figure 1

Schematic diagram of class 1 integrons from Stenotrophomonas maltophilia isolates. A), isolates 1893 and 9431. B) isolates 489, 9189, and 12221; C) isolates 3438 and 3444. Arrows depict direction of transcription, and shaded boxes represent gene cassettes found within the integron. The dark circles represent the 59-bp region immediately 5′ to the incorporated gene cassette.

Figure 2

Genetic context of various insertion element common region (ISCR2) elements. Schematic of various GenBank sequences that harbor the ISCR2 element. Open reading frames (ORFs) are depicted as open boxes with the direction of transcription of the various ORF indicated with arrows. The ORF of the ISCR2 transposase is highlighted, and the limits of the ISCR2 element are shown with vertical lines. The ISCR2 element consists of an ORF of 1491 bp together with ≈120 bp of upstream sequence and ≈240 bp of downstream sequence. The ISCR2 element identified in this study associated with the floR resistance gene is amplified to show primer sites and positions of the putative oriIS and terIS of the ISCR2 element. The bold arrow indicates the direction of rolling circle replication of the ISCR2 element. GenBank accession numbers of the various sequences are indicated. P., Pasteurella; A., Aeromonas; S. enterica, Salmonella enterica; S. maltophilia, Stenotrophomonas maltophila. *This study.