Molecular basis of macrolide resistance among Pasteurella multocida and Mannheimia haemolytica isolates
Parasitology and Biology of Tropical Infectious Disease Pathogens
Final Report Abstract
The aims of this study were (i) to identify the macrolide resistance mechanism(s) in M. haemolytica isolates that do not harbor known macrolide resistance mechanisms, (ii) to analyze ICEs in Pasteurellaceae for structural variabilities in their resistance gene regions and investigate the potential of ICEs as accumulators and distributers of resistance genes, but also (iii) to analyse the first macrolide-resistant Pasteurellaceae isolates from Germany. A single macrolide resistance mechanism was not found, but the results gave important hints towards a synergistic interaction among resistance mechanisms, as (i) the alteration of membrane permeability, (ii) interaction between overexpressed membrane proteins with efflux pumps and (iii) high rate of ribosome synthesis. Such investigations are important for the development of novel macrolide antibiotics or improve current antibiotics. The analysis of ICEs in Pasteurellaceae revealed that in spite the high diversity of ICE-associated resistance gene regions and their arrangements the close similarity of the backbone regions suggests a common evolutionary origin of the investigated ICEs. Moreover, the co-location of resistance genes on mobile elements capable of conjugative transfer across genus boundaries represents a serious threat and may (i) drastically limit the options of an efficient antimicrobial therapy of respiratory tract infections in food-producing animals and (ii) further the development of pan-resistant Pasteurellaceae, which cannot be treated anymore with antimicrobial agents. These findings are important to support monitoring programs for veterinary bacterial pathogens and are helpful for the interpretation of the trends in the development of antimicrobial resistance.
Publications
- Analysis and comparison of the first integrative and conjugative element (ICE) of Mannheimia haemolytica, the ICEMh1. International Pasteurellaceae Conference (IPC), 13.-16.05.2014, Prato, Italy
Eidam C, Poehlein A, Leimbach A, Michael GB, Liesegang H, Kadlec K, Daniel R, Sweeney MT, Murray RW, Watts JL, Schwarz S
- First tulathromycin-resistant Pasteurellaceae isolates from Germany. Meeting of the Deutschen Veterinärmedizinischen Gesellschaft (DVG) Fachgruppe „Bakteriologie und Mykologie”, 26.-28.05.2014, Freising, Germany
Eidam C, Kadlec K, Michael GB, Kaspar H, Schwarz S
- ICEMh1, the first integrative and conjugative element (ICE) of Mannheimia haemolytica. 7th International Conference on Antimicrobial Agents in Veterinary Medicine (AAVM), 16.-19.09.2014, Berlin, Germany
Eidam C, Poehlein A, Leimbach A, Michael GB, Liesegang H, Kadlec K, Daniel R, Sweeney MT, Murray RW, Watts JL, Schwarz S
- Integrative and conjugative elements (ICEs) conferring multi-resistance in bovine Pasteurella multocida and Mannheimia haemolytica. 7th International Conference on Antimicrobial Agents in Veterinary Medicine (AAVM) 16.-19.09.2014, Berlin, Germany
Michael GB, Eidam C, Sweeney MT, Murray RW, Poehlein A, Leimbach A, Liesegang H, Daniel R, Watts JL, Schwarz S, Kadlec K
- Structural variations in the resistance gene regions of the integrative and conjugative element ICEPmu1 from bovine Pasteurella multocida and Mannheimia haemolytica. 7th International Conference on Antimicrobial Agents in Veterinary Medicine (AAVM) 2014, 16.-19. September, Berlin, Germany
Michael GB, Sweeney MT, Murray RW, Watts JL, Schwarz S, Kadlec K
- Analysis and comparative genomics of ICEMh1, a novel integrative and conjugative element (ICE) of Mannheimia haemolytica. 4th ASM Conference on Antimicrobial Resistance in Zoonotic Bacteria and Foodborne Pathogens in Animals, Humans and the Environment, 08.-11.05.2015, Washington DC, USA
Eidam C, Poehlein A, Leimbach A, Michael GB, Liesegang H, Kadlec K, Daniel R, Sweeney MT, Murray RW, Watts JL, Schwarz S
- Analysis and comparative genomics of ICEMh1, a novel integrative and conjugative element (ICE) of Mannheimia haemolytica. J Antimicrob Chemother. 2015, 70:93-97
Eidam C, Poehlein A, Leimbach A, Michael GB, Kadlec K, Liesegang H, Daniel R, Sweeney MT, Murray RW, Watts JL, Schwarz S
(See online at https://doi.org/10.1093/jac/dku361) - A novel multiresistance integrative and conjugative element ICEPmu2 in a Pasteurella multocida isolate from Germany. Meeting of the Deutschen Veterinärmedizinischen Gesellschaft (DVG) Fachgruppe „Bakteriologie und Mykologie”, 31.08-02.09.2016, Jena. Germany
Kadlec K, Li J, Kaspar H, Shen Y, Wang Y, Schwarz S
- Identification of a novel multiresistance integrative and conjugative element ICEPmu2 in a bovine Pasteurella multocida isolate from Germany. 7th Symposium on Antimicrobial Resistance in Animals and the Environment (ARAE), 26.-28.06.2017, Braunschweig, Germany
Kadlec K, Li J, Michael GB, Kaspar H, Shen Y, Wang Y, Schwarz S
- Antimicrobial resistance in Pasteurellaceae of veterinary origin. Microbiol Spectr. 2018, 6(3)
Michael GB, Bossé JT, Schwarz S
(See online at https://doi.org/10.1128/microbiolspec.ARBA-0022-2017)
