A preliminary exploration on the mechanism of the carbapenem-resistance transformation of Serratia marcescens in vivo

Abstract

Abstract Background The infection of carbapenem-resistant organisms was a huge threat to human health due to their global spread. Dealing with a carbapenem-resistant Serratia marcescens (CRSM) infection poses a significant challenge in clinical settings. This study aims to provide insights into strategies for controlling CRSM infection by exploring the transformation mechanism of carbapenem-resistance. Methods We used whole genome sequencing (WGS) to investigate the mechanism of carbapenem resistance in 14 S. marcescens isolates in vivo. The expression level of related genes and the minimum inhibitory concentration of meropenem (MICMEM) were also evaluated to confirm the mechanism of carbapenem resistance. Results Seven groups of S. marcescens, each consisting of two strains, were collected from a hospital and displayed a shift in MICMEM from low to high levels. Homology analysis revealed that the isolates in five groups were significantly different from the remaining two. WGS and experimental evidence indicated that four groups of strains developed carbapenem resistance by acquiring the bla KPC (obtaining group), while two groups (persisting group) increased the expression level of the bla KPC. In contrast, isolates in the last group (missing group) did not carry the bla KPC. All strains possessed multiple β-lactamase genes, including bla CTX−M−14, bla SRT−1, and bla SRT−2. However, only in the missing group, the carbapenem-resistant strain lost an outer membrane protein-encoding gene, leading to increased bla CTX−M−14 expression compared to the carbapenem-susceptible strain. Conclusion The study findings suggest that S. marcescens strains developed diverse carbapenem resistance in vivo through the evolution of drug resistance, rather than through clone replacement. We hypothesize that carbapenem resistance in S. marcescens was due to certain clonal types with a distinct mechanism.

Keywords

• Serratia marcescens
• Carbapenem-resistance
• bla KPC