Publikationsdatenbank

Transfer and structural alterations of resistance plasmids carrying carbapenemase-encoding genes in a broiler chicken infection model (2020)

Art

Hochschulschrift

Autor

Hadziabdic, Sead (WE 10)

Quelle

Berlin: Mensch und Buch Verlag, 2020 — vi, 132 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/28558

Kontakt

Institut für Tier- und Umwelthygiene

Robert-von-Ostertag-Str. 7-13
14169 Berlin
+49 30 838 51845
tierhygiene@vetmed.fu-berlin.de

Abstract / Zusammenfassung

The antimicrobial resistance remains an important threat to the public and animal health. The current trends of antimicrobial resistance reveal an alarming and ongoing dissemination of associated genes to different bacteria. With the aim of preserving important antimicrobials for human treatment, certain antimicrobial classes, such as carbapenems are categorized as critically important antimicrobials and are not licensed for use in foodproducing animals. However, in recent years, reports of carbapenemase-producing bacteria in livestock animals started to emerge. In Germany, several studies reported detection of carbapenemase-producing enterobacteria in wild birds, livestock, meat and seafood products. An important observation was association of New Delhi Metallo (NDM-1) and Verona Integron Metallo (VIM-1) carbapenemases to different Salmonella serovars, suggesting their role as reservoirs of these carbapenemases. Motivated by the detection of carbapenemase-producing Salmonella serovars in a wild bird and poultry production, in this doctoral thesis scenarios of avian native NDM-1-producing Salmonella enterica subsp. enterica serovar (S.) Corvallis and VIM-1-producing S. Infantis entering a broiler flock were investigated. The aim of the in vivo studies was to understand behavior of these strains and their plasmids in the absence of antibiotic pressure. Particular focus was on the in vivo spread and stability of carbapenemase-encoding blaNDM-1-carrying plasmids belonging to the incompatibility group A/C2 (IncA/C2) and blaVIM-1-carrying plasmids belonging to group HI2 (IncHI2). The insight into transfer and structural alteration of plasmids was obtained by an in-depth molecular analysis with S1-pulsed-field gel electrophoresis plasmid profiling and subsequent short and long-read whole genome sequencing analysis. The in vivo studies showed that in a scenario of NDM-1-producing S. Corvallis entering a broiler flock, the blaNDM-1-carrying IncA/C2 plasmid disseminates to different gut enterobacteria, such as Escherichia (E.) coli and Klebsiella (K.) pneumoniae, in the absence of antibiotic pressure. The acquisition of this plasmid was not restricted to a particular E. coli clone, as this plasmid was detected in different E. coli ST-types and a K. pneumoniae strain. The blaNDM-1-carrying IncA/C2 plasmid remained detected in donor and E. coli strains until the end of trial, revealing stable persistence of this plasmid also in new hosts. Although less frequent in contrast to gut enterobacteria, acquisition of the blaNDM-1-carrying IncA/C2 plasmid in broiler-associated S. Paratyphi B (dTartrate-positive) and S. Infantis strains was detected. Acquisition of the blaVIM-1-carrying IncHI2 plasmid was not detected in other bacteria during the course of in vivo study. As for the in vivo stability of blaNDM-1-carrying IncA/C2 and blaVIM-1-carrying IncHI2 plasmid, stable persistence of these plasmids in their native hosts was observed. In the case of blaNDM-1-carrying IncA/C2 plasmid a smaller (~10 kb) and larger (~70 kb) structural deletion was identified, along with formation of a newly emerged blaNDM-1-carrying IncA/C2-IncHI2 multireplicon megaplasmid. Despite structural alterations, the blaNDM-1 gene was maintained in these variants of the blaNDM-1-carrying IncA/C2 plasmid. In the selection of blaVIM-1-carrying IncHI2 plasmids, from donor reisolates, smaller (~10 kb) structural deletions were observed. In conclusion, the in vivo broiler chicken infection studies revealed stable persistence of the blaNDM-1-carrying IncA/C2 and blaVIM-1-carrying IncHI2 plasmids, despite sporadic structural alterations, in their hosts in a scenario of entry into a broiler flock. As for blaNDM-1-carrying IncA/C2 plasmid, a worrying observation is the rapid and broad dissemination of the blaNDM-1-carrying IncA/C2 plasmid to gut enterobacteria and Salmonella recipients in the absence of selective pressure. Although here primarily investigating the behavior of NDM-1-producing S. Corvallis and VIM-1-producing S. Infantis strains, the results can serve as a model for the potential dissemination of other MDR-encoding broad host range plasmids in a broiler flock. Therefore, important preventive measure should be achieved to avoid such bacteria entering a broiler flock, as their entrance could lead to the spread of MDR-encoding plasmids even in the absence of antibiotic pressure.