Antimicrobial Resistance in Bordetella bronchiseptica

Abstract

Bordetella bronchiseptica is involved in respiratory tract infections mainly in dogs and pigs but may also cause infections in humans. Valid and representative data on antimicrobial susceptibility of B. bronchiseptica is rare. Approved antimicrobial susceptibility testing methods have been published, but very few clinical breakpoints are available. The MIC values are low for most agents but high for β-lactam antibiotics and macrolides. Information on the genetic basis of resistance is scarce. For a small number of isolates that are resistant or show elevated MICs, the molecular basis of resistance was identified. Three tetracycline resistance genes, tet(A), tet(C), and tet(31), coding for major facilitator superfamily efflux pumps, were identified. Two other major facilitator superfamily exporter genes confer resistance to chloramphenicol (cmlB1) or to chloramphenicol and florfenicol (floR). Two class B chloramphenicol acetyltransferase genes (catB1 and catB3), which confer resistance to nonfluorinated phenicols by enzymatic inactivation, have been identified in B. bronchiseptica. Like the trimethoprim resistance genes dfrA1 and dfrB1, which code for trimethoprim-insensitive dihydrofolate reductases, the genes catB1 and catB3 were located on gene cassettes and found in class 1 integrons also harboring the sulfonamide resistance gene sul1. In addition, the gene sul2 has also been detected. Both sul1 and sul2 code for sulfonamide-insensitive dihydropteroate synthases. A gene cassette harboring the β-lactamase gene bla_OXA-2 was also identified, whereas β-lactam resistance in B. bronchiseptica seems to be more likely due to reduced influx in combination with the species-specific β-lactamase encoded by bla_BOR-1. The resistance genes were mostly located on conjugative plasmids.

FIGURE 1

Schematic presentation of the class 1 integrons described so far in B. bronchiseptica isolates. The reading frames of the antimicrobial resistance genes are shown as arrows, and the conserved segments of the class 1 integron are shown as boxes. The beginning and the end of the integrated cassettes are shown in detail below. The translational start and stop codons are underlined. The 59-base elements are shown in bold type, and the putative IntI1 integrase binding domains 1L, 2L, 2R, and 1R are indicated by arrows. The numbers refer to the positions of the bases in the EMBL database entries with the following accession numbers: (a) AJ844287, (b) AJ879564, and (c) AJ877267 (41, 50).

FIGURE 2

Comparison of Tn1721 (GenBank accession no. X61367) and the sequenced parts of the resistance plasmids pKBB958 (GenBank accession no. AM183165) and pKBB4037 (GenBank accession no. AJ877266) from B. bronchiseptica. A distance scale in kb is given below each map. The genes tetR, tet(A), mcp, tnpR, tnpA, ΔtnpA, res, parA1, parC, and ΔtnpA* are presented as arrows, with the arrowhead indicating the direction of transcription. The Δ symbol indicates a truncated, functionally inactive gene. The black boxes represent the terminal or internal 38-bp repeats of Tn1721. The gray shaded areas indicate the homologous parts between the B. bronchiseptica plasmids and Tn1721 (26).