Publikationsdatenbank

Comparative phenotypic and genotypic studies on LA-MRSA CC398 and CC9 of pigs from Germany and China (2023)

Art

Hochschulschrift

Autor

Krüger-Haker, Henrike (WE 7)

Quelle

Berlin, 2023 — XIV, 142 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/41877

Kontakt

Institut für Mikrobiologie und Tierseuchen

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51843 / 66949
mikrobiologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) are opportunistic zoonotic pathogens that have been globally recognized as a health threat in human and veterinary medicine. They are known for their common multiresistance to antimicrobial agents and may cause severe diseases although normally lacking major virulence factors. Colonized pigs and their related surroundings represent a considerable LA-MRSA reservoir. Due to their low host specificity, LA-MRSA isolates can easily cross species barriers. Therefore, persons with frequent (occupational) exposure to pigs have an increased risk of LA-MRSA colonization and/or infection and they may further transmit these isolates to contact persons and animals. The LA-MRSA prevalence differs geographically: Clonal Complex (CC) 398 dominates among pigs in Europe, Australia and the Americas, whereas CC9 is the most common lineage among pigs in Asia. This thesis revealed that differences in metabolic properties did most likely not play a key role in the development of the aforementioned two different epidemic porcine LA-MRSA clones in Germany and China, respectively. However, it was hypothesized that LA-MRSA CC398 might gradually replace the currently dominating CC9 lineage in China in the future because of many beneficial features that may enable preferential survival of the CC398 lineage under hostile environmental conditions or in the host. Possibly unfavorable metabolic variations and a lower growth rate of the Chinese LA-MRSA CC9 clone may be disadvantageous in niche adaptation and, thus, may support the replacement process. Consequently, the public health risk originating from porcine LA-MRSA might rise because of the increased pathogenicity of the CC398 lineage. Moreover, this thesis provided insight into population dynamics and molecular diversity of the epidemic porcine LA-MRSA CC398 lineage in Germany over 13 years in comparison with the porcine LA-MRSA CC9 lineage dominating in China. In general, both clones exhibited typical individual characteristics, but also some novel features. During comparison, similarities as well as distinct differences were recognized between the two lineages. The German CC398 isolates were widespread within Germany and largely reflected the pig density of the different regions. They displayed a wide molecular diversity and rather close phylogenetic relationships. An ongoing diversification was recognized over time. The CC398 and CC9 lineage both displayed a clear virulence potential, although genes coding for the major virulence factors Panton-Valentine leucocidin and toxic shock syndrome toxin-1 were not detected. Moreover, both lineages exhibited a great variety of AMR properties that mirrored the respective sales figures of veterinary antimicrobial agents in the two countries. The AMR profiles of the Chinese isolates were more extensive. In both lineages, AMR was largely associated with mobile genetic elements (MGEs), which can be transferred easily across strain, species or even genus boundaries via horizontal gene transfer (HGT). However, the German CC398 isolates displayed a greater variety of different MGEs, which points towards the easier integration of foreign genetic material. In addition, clonal and geographical correlations of molecular characteristics, virulence and resistance properties were more frequently observed among the LA-MRSA CC398 from Germany than temporal correlations. Furthermore, multiple novel MGEs were characterized in this thesis. A novel type V variant of the methicillin-resistance mediating SCCmec cassette was identified in a porcine LA-MRSA CC398 isolate from China. Homologies with other type V and XII elements indicate an ongoing evolution of SCCmec elements in LA-MRSA CC398 from pigs. Tn553 and Tn560 represent two new members of the Tn554 transposon family detected in Chinese LA-MRSA CC9 and CC398 isolates, respectively. Tn553 harbored a complete beta-lactam resistance mediating blaZ-blaR1-blaI beta-lactamase operon and preferred a different integration site than former Tn554-related transposons. Tn560 carried a multiresistance gene cluster comprising the spectinomycin resistance gene spcV, a novel spc variant that is most likely the product of a recombination between the related spc and spw genes, the pleuromutilin-lincosamide-streptogramin A resistance gene lsa(E) and the lincosamide resistance gene lnu(B). Plasmid pHKS3860 from a German porcine LA-MRSA CC398 isolate harbored the novel macrolide-lincosamide-streptogramin B resistance gene erm(54), cadmium, mercury and copper resistance genes, as well as an ica gene cluster for biofilm formation. As a consequence of such co-localizations on the same MGE, multiple resistance and/or virulence properties can be transferred in a single event. Even in the absence of a direct selection pressure, the risk for co-selection processes is increased. Finally, this thesis expanded the knowledge on the epidemic porcine LA-MRSA lineages in Germany and China. They represent a considerable AMR repository adding to the global health threat posed by AMR with HGT as major driver of rapid dissemination. Moreover, the understanding of genetic rearrangements in LA-MRSA and how these bacteria exchange genetic material has been improved. The diversity of LA-MRSA further increases and new emerging and possibly more virulent and/or resistant variants should be closely monitored. Due to the zoonotic potential and the risk of further spread among pig husbandries and into the human community, a full-scale LA-MRSA surveillance is vitally important.