Integrative and conjugative elements associated with antimicrobial resistance in multidrug resistant Pasteurella multocida isolates from bovine respiratory disease (BRD)-affected animals in Spanish feedlots

Abstract

The emergence of multidrug-resistance (MDR) in Pasteurella multocida, a major contributor to bovine respiratory disease (BRD) is being increasingly reported, often linked to the carriage of antimicrobial resistance genes (ARGs) on integrative and conjugative elements (ICEs). The resistance phenotype for 19 antimicrobials was determined using broth microdilution in 75 Pasteurella multocida isolates from healthy and BRD-affected cattle from five feedlots. The genomes of 32 isolates were sequenced to identify ARG) and mobile genetic elements (MGEs) and assess their genetic diversity. MDR isolates (with phenotypic resistance to aminoglycosides, macrolides, fluoroquinolones and/or tetracyclines) were primarily found among BRD-affected compared to healthy animals. Non-susceptible isolates, belonging to ST79 and ST13, harbored point mutations and four to nine ARGs, including rarely reported mechanisms in Europe (mph(E), msr(E) and aadA31 ARGs and newly described mutations in the gyrA/parC genes). All ARGs were linked to the presence of MGEs including two ICEs, Tn7407 and the novel Tn7809, a prophage and a putative composite transposon. Clonally related isolates were found in different batches from the same feedlot, suggesting maintenance of MDR strains. Our findings demonstrate the diverse genetic basis of AMR in P. multocida from BRD-affected cattle in Spain, emphasizing the role of MGEs in the ARG dissemination.