Dataset Information

Combinations of macrolide resistance determinants in field isolates of Mannheimia haemolytica and Pasteurella multocida.

ABSTRACT: Respiratory tract infections in cattle are commonly associated with the bacterial pathogens Mannheimia haemolytica and Pasteurella 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 the erm(42) gene. The second class shows no lincosamide resistance and lacks erm(42) and concomitant 23S rRNA methylation. Sequencing of the genome of a representative strain from this class, P. multocida 3361, revealed macrolide efflux and phosphotransferase genes [respectively termed msr(E) and mph(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 of erm(42), msr(E), and mph(E) are chromosomally encoded and intermingled with other exogenous genes, many of which appear to have been transferred from other members of the Pasteurellaceae. The presence of some of the exogenous genes explains recent reports of resistance to additional drug classes. We have expressed recombinant versions of the erm(42), msr(E), and mph(E) genes within an isogenic Escherichia coli background to assess their individually contributions to resistance. Our findings indicate what types of compounds might have driven the selection for these resistance determinants.

SUBMITTER: Desmolaize B

PROVIDER: S-EPMC3165316 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Combinations of macrolide resistance determinants in field isolates of Mannheimia haemolytica and Pasteurella multocida.

Desmolaize Benoit B Rose Simon S Wilhelm Cornelia C Warrass Ralf R Douthwaite Stephen S

Antimicrobial agents and chemotherapy 20110627 9

Respiratory tract infections in cattle are commonly associated with the bacterial pathogens Mannheimia haemolytica and Pasteurella 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 resis ...[more]

PMID: 21709086

Similar Datasets

Project description:The mosaic structure and molecular evolution of the leukotoxin operon (lktCABD) was investigated by nucleotide sequence comparison of the lktC, lktB, and lktD genes in 23 Mannheimia (Pasteurella) haemolytica, 6 Mannheimia glucosida, and 4 Pasteurella trehalosi strains. Sequence variation in the lktA gene has been described previously (R. L. Davies et al., J. Bacteriol. 183:1394-1404, 2001). The leukotoxin operon of M. haemolytica has a complex mosaic structure and has been derived by extensive inter- and intraspecies horizontal DNA transfer and intragenic recombination events. However, the pattern of recombination varies throughout the operon and among the different evolutionary lineages of M. haemolytica. The lktA and lktB genes have the most complex mosaic structures with segments derived from up to four different sources, including M. glucosida and P. trehalosi. In contrast, the lktD gene is highly conserved in M. haemolytica. The lktC, lktA, and lktB genes of strains representing the major ovine lineages contain recombinant segments derived from bovine or bovine-like serotype A2 strains. These findings support the previous conclusion that host switching of bovine A2 strains from cattle to sheep has played a major role in the evolution of the leukotoxin operon in ovine strains of M. haemolytica. Homologous segments of donor and recipient alleles are identical, or nearly identical, indicating that the recombinational exchanges occurred relatively recent in evolutionary terms. The 5' and 3' ends of the operon are highly conserved in M. haemolytica, which suggests that multiple horizontal exchanges of the complete operon have occurred by a common mechanism such as transduction. Although the lktA and lktB genes both have complex mosaic structures and high nucleotide substitution rates, the amino acid diversity of LktB is significantly lower than that of LktA due to a higher degree of evolutionary constraint against amino acid replacement. The recombinational exchanges within the leukotoxin operon have had greatest effect on LktA and probably provide an adaptive advantage against the host antibody response by generating novel antigenic variation at surface-exposed sites.

Project description:A cross-sectional study was undertaken in four (4) districts of the West Amhara sub-region of Ethiopia with the aim of assessing the diversity and distribution of serotypes of Pasteurella species, their seroprevalence, and associated risk factors, and knowledge, attitude, and practice of farmers toward ovine pasteurellosis. A total of 600 sheep sera were collected using multistage cluster sampling. Each sample was examined for the presence of six (6) serotype-specific antibodies using an indirect haemagglutination test. We are reporting a higher seroprevalence of 90.17% (541/600) in which all seropositive animals were shown to have been co-infected with multiple serotypes. Individual serotype prevalence showed that serotype A7 has the highest prevalence of 77.83% followed by A2 (74.33%), T15 (64%), T4 (62%), PA (60%), and A1 (39.17%). In this study, being female [odds ratio (OR): 2.45, 95% CI (1.09-5.52), p = 0.031] and living in high altitude areas [OR: 20.29, 95% CI (2.54-161.95), p = 0.004] were found to be significantly associated with sero-positivity. A questionnaire survey (n = 384) employed in a face-to-face interview was used to assess the knowledge, attitude, and practice of farmers related to ovine pasteurellosis. Accordingly, the majority (72.4%) of respondents had an inadequate knowledge level of the disease. The proportion of farmers with a favorable attitude and good practices toward the disease was 50.26 and 77.6%, respectively. This study is highly indicative that ovine pasteurellosis is a ubiquitous disease in the study area challenging the sheep production sector. The existence of diverse serotypes reported to lack cross-protective immunity is likely to explain why the current vaccination practice with the mono-serotype Pasteurella multocida biotype A vaccine is not providing adequate protection against outbreaks of the disease. Prioritization of one or more serotypes for inclusion in a multivalent vaccine should be dictated by the abundance and distribution of a particular serotype, its clinical importance, and its resultant economic impact. Furthermore, training farmers on key aspects of the disease is vital in the implementation of effective disease management strategies through a participatory approach. Data from the remaining regions of the country could help realize the development of an effective vaccine that works best at the national level.

Project description:The OmpA (or heat-modifiable) protein is a major structural component of the outer membranes of gram-negative bacteria. The protein contains eight membrane-traversing beta-strands and four surface-exposed loops. The genetic diversity and molecular evolution of OmpA were investigated in 31 Mannheimia (Pasteurella) haemolytica, 6 Mannheimia glucosida, and 4 Pasteurella trehalosi strains by comparative nucleotide sequence analysis. The OmpA proteins of M. haemolytica and M. glucosida contain four hypervariable domains located at the distal ends of the surface-exposed loops. The hypervariable domains of OmpA proteins from bovine and ovine M. haemolytica isolates are very different but are highly conserved among strains from each of these two host species. Fourteen different alleles representing four distinct phylogenetic classes, classes I to IV, were identified in M. haemolytica and M. glucosida. Class I, II, and IV alleles were associated with bovine M. haemolytica, ovine M. haemolytica, and M. glucosida strains, respectively, whereas class III alleles were present in certain M. haemolytica and M. glucosida isolates. Class I and II alleles were associated with divergent lineages of bovine and ovine M. haemolytica strains, respectively, indicating a history of horizontal DNA transfer and assortative (entire gene) recombination. Class III alleles have mosaic structures and were derived by horizontal DNA transfer and intragenic recombination. Our findings suggest that OmpA is under strong selective pressure from the host species and that it plays an important role in host adaptation. It is proposed that the OmpA protein of M. haemolytica acts as a ligand and is involved in binding to specific host cell receptor molecules in cattle and sheep. P. trehalosi expresses two OmpA homologs that are encoded by different tandemly arranged ompA genes. The P. trehalosi ompA genes are highly diverged from those of M. haemolytica and M. glucosida, and evidence is presented to suggest that at least one of these genes was acquired by horizontal DNA transfer.

Dataset Information

Combinations of macrolide resistance determinants in field isolates of Mannheimia haemolytica and Pasteurella multocida.

Publications

Combinations of macrolide resistance determinants in field isolates of Mannheimia haemolytica and Pasteurella multocida.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets