Laboratory Medicine Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, National Clinical Research Center for Infectious Diseases, Zhejiang University, NO.79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China.
BMC Genomics. 2024 Jan 2;25(1):2. doi: 10.1186/s12864-023-09904-2.
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.
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 (MIC) were also evaluated to confirm the mechanism of carbapenem resistance.
Seven groups of S. marcescens, each consisting of two strains, were collected from a hospital and displayed a shift in MIC 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 (obtaining group), while two groups (persisting group) increased the expression level of the bla. In contrast, isolates in the last group (missing group) did not carry the bla. All strains possessed multiple β-lactamase genes, including bla, bla, and bla. However, only in the missing group, the carbapenem-resistant strain lost an outer membrane protein-encoding gene, leading to increased bla expression compared to the carbapenem-susceptible strain.
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.
由于碳青霉烯类耐药菌在全球范围内的传播，其感染对人类健康构成了巨大威胁。在临床环境中，应对碳青霉烯类耐药的阴沟肠杆菌（CRSM）感染是一项重大挑战。本研究旨在通过探索碳青霉烯类耐药的转化机制，为控制 CRSM 感染提供策略。
我们使用全基因组测序（WGS）技术研究了 14 株阴沟肠杆菌体内碳青霉烯类耐药的机制。还评估了相关基因的表达水平和美罗培南的最小抑菌浓度（MIC），以确认碳青霉烯类耐药的机制。
从一家医院收集了七组每组由两株组成的阴沟肠杆菌，其 MIC 水平从低到高发生了转变。同源性分析表明，五组分离株与其余两组有显著差异。WGS 和实验证据表明，四组菌株通过获得 bla（获得组）而产生碳青霉烯类耐药性，而两组（持续组）增加了 bla 的表达水平。相比之下，最后一组（缺失组）分离株未携带 bla。所有菌株均携带多种β-内酰胺酶基因，包括 bla、bla 和 bla。然而，只有在缺失组中，碳青霉烯类耐药菌株失去了一个外膜蛋白编码基因，导致 bla 的表达水平高于碳青霉烯类敏感菌株。
研究结果表明，阴沟肠杆菌菌株在体内通过耐药进化而不是通过克隆替换产生了不同的碳青霉烯类耐药性。我们假设阴沟肠杆菌的碳青霉烯类耐药性是由具有独特机制的某些特定克隆类型引起的。
