The Roles of a Multidrug-Resistant Klebsiella pneumoniae High-Risk Clone and Its Resistance Plasmids on the Gastrointestinal Colonization and Host-Defense Effectors in the Gut

Stercz, Balázs and Domokos, Judit and Dunai, Zsuzsanna and Makra, Nóra and Juhász, János and Ostorházi, Eszter and Kocsis, Béla and Szabó, Dóra (2024) The Roles of a Multidrug-Resistant Klebsiella pneumoniae High-Risk Clone and Its Resistance Plasmids on the Gastrointestinal Colonization and Host-Defense Effectors in the Gut. ANTIBIOTICS, 13 (8). No.-698. ISSN 2079-6382

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Abstract

The asymptomatic gastrointestinal colonization of multidrug-resistant (MDR) bacteria can lead to difficult-to-treat infections. We investigated the role of host factors influencing colonization in an orogastrical murine infection model using a CTX-M-15- and OXA-162-producing Klebsiella pneumoniae ST15 (MDR-KP) strain, as well as Escherichia coli J53 (EC) and E. coli transconjugants with an IncFII(K) plasmid carrying CTX-M-15 (EC-CTXM), and with an IncL plasmid carrying OXA-162 (EC-OXA) genes. The fecal bacterial count in colony-forming unit/gram stool (CFU/g) was determined by cultivation, IgA and defensin levels by ELISA, and gut microbiota by 16S rRNA analysis. The CFU was the lowest in EC, followed by EC-OXA and EC-CTXM, and the highest in the MDR-KP group. The IgA level in feces increased in MDR-KP, EC-CTXM, and EC-OXA, and did not change in EC. The beta-defensin 3 level markedly increased in all groups, with the highest values in MDR-KP and EC-CTXM. Alpha-defensin-5 increased in all groups especially in EC. In microbiota, the Bacteroidota phylum was dominant in MDR-KP, EC-CTXM, and EC-OXA, whereas Proteobacteria was dominant in EC. The Muribaculaceae family was significantly more common in the MDR-KP and EC-OXA groups, while the Lachnospiraceae family was dominant in the EC group. While fecal IgA levels positively correlated with colonizing bacterial CFU, the alpha-defensin 5 levels inversely correlated with CFUs and IgA levels. The presence of the IncFII(K) plasmid induced beta-defensin 3 production. The amounts of the Muribaculaceae family members exhibited a correlation with the IncL plasmid. The detected amounts of the Lachnospiraceae family indicated the protective role against the high-risk clone and the resistance plasmids’ dissemination. Our results suggest that not only the MDR-KP clone itself but also the resistance plasmids play a primary role in the colonization rate in the gastrointestinal tract. Both the MDR-KP clone as well as the IncFII(K) and IncL resistance plasmids provide survival and colonization benefits in the gut.

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