The role of resistance plasmids influencing gastrointestinal colonization of multidrug resistant Klebsiella pneumoniae in murine model
Stercz Balázs
Pathological Sciences
Dr. Matolcsy András
SE Bőr-, Nemikórtani és Bőronkológiai Klinika előadóterme
2025-10-15 14:00:00
Mikroorganizmusok és anyagaik hatásainak molekuláris, celluláris és organizmus szintű vizsgálata
Dr. Szabó Dóra
Dr. Szabó Dóra
Dr. Urbán Edit
Dr. Földvári-Nagy Lászlóné Lenti Katalin
Dr. Hegyesi Hargita
Dr. Gecse Kinga
Dr. Csire Márta
Antimicrobial resistance (AMR) poses a critical global health challenge. Horizontal gene transfer (HGT) plays a key role in spreading resistance genes, such as those encoding β-lactamases. Multidrug resistant (MDR) bacteria can colonize asymptomatically the gastrointestinal tract, which is a multifactorial process influenced by host factors too. This study investigated the colonization dynamics of MDR K. pneumoniae, focusing on plasmid-mediated resistance and the host immune response.
The research utilized MDR K. pneumoniae ST15 harboring several plasmids including an IncFII(K) encoding blaCTX-M-15 and an IncL encoding blaOXA-162 (MDR-KP), its transconjugant E. coli strains harboring only one of the mentioned plasmids (EC-CTXM, EC-OXA) and a plasmid free E. coli strain (EC). Their resistance to antibiotics were investigated using broth microdilution. In murine model, following gastrointestinal colonization of mice fecal germ count, total IgA, murine β-defensin 3 (mBD3), murine α-defensin 5 (mAD5) were measured and 16S metagenomic analysis was carried out.
Colonization experiments revealed that resistance plasmid-carrying strains colonized the gastrointestinal tract more effectively than non-resistant strains, triggering stronger immune responses. The MDR group showed the highest bacterial colonization accompanied by elevated fecal IgA and defensin levels.
Carriage of plasmids both colonization efficiency and antimicrobial responses. MDR-KP and EC-CTXM strains strongly induced mBD3 and IgA production, while EC-OXA strain suppressed both mBD3 and mAD5, however IgA induction was strong. The non-resistant EC strain has a limited colonizing capacity and induced only mAD5. Microbiota composition analysis revealed dominance of Bacteroidota in MDR-associated groups and Firmicutes in non-resistant EC strain, with specific families like Muribaculaceae and Lachnospiraceae correlating with plasmid presence and colonization outcomes.
These findings highlight the dual role of high-risk MDR clones and resistance plasmids in gut colonization and immune modulation, demonstrating that resistance plasmids not only enhance bacterial survival but also shape immune responses. The results provide novel insights into the interplay between plasmids, host immunity, and microbiota, emphasizing the need for targeted strategies to combat AMR.
