Combinations of Macrolide Resistance Determinants in Field Isolates of Mannheimia haemolytica and Pasteurella multocida

Abstract

ABSTRACTRespiratory tract infections in cattle are commonly associated with the bacterial pathogensMannheimia haemolyticaandPasteurella multocida. These infections can generally be successfully treated in the field with one of several groups of antibiotics, including macrolides. A few recent isolates of these species exhibit resistance to veterinary macrolides with phenotypes that fall into three distinct classes. The first class has type I macrolide, lincosamide, and streptogramin B antibiotic resistance and, consistent with this, the 23S rRNA nucleotide A2058 is monomethylated by the enzyme product of theerm(42) gene. The second class shows no lincosamide resistance and lackserm(42) and concomitant 23S rRNA methylation. Sequencing of the genome of a representative strain from this class,P. multocida3361, revealed macrolide efflux and phosphotransferase genes [respectively termedmsr(E) andmph(E)] that are arranged in tandem and presumably expressed from the same promoter. The third class exhibits the most marked drug phenotype, with high resistance to all of the macrolides tested, and possesses all three resistance determinants. The combinations oferm(42),msr(E), andmph(E) are chromosomally encoded and intermingled with other exogenous genes, many of which appear to have been transferred from other members of thePasteurellaceae. The presence of some of the exogenous genes explains recent reports of resistance to additional drug classes. We have expressed recombinant versions of theerm(42),msr(E), andmph(E) genes within an isogenicEscherichia colibackground to assess their individually contributions to resistance. Our findings indicate what types of compounds might have driven the selection for these resistance determinants.