Polani Riccardo, De Francesco Alice, Tomolillo Dario, Artuso Irene, Equestre Michele, Trirocco Rita, Arcari Gabriele, Antonelli Guido, Villa Laura, Prosseda Gianni, Visca Paolo, Carattoli Alessandra
Emerg Infect Dis. 2025 Jan;31(1):123-124. doi: 10.3201/eid3101.241426.
Cefiderocol (FDC), a siderophore-cephalosporin conjugate, is the newest option for treating infection with carbapenem-resistant gram-negative bacteria. We identified a novel mechanism contributing to decreased FDC susceptibility in Klebsiella pneumoniae clinical isolates. The mechanism involves 2 coresident plasmids: pKpQIL, carrying variants of bla carbapenemase gene, and pKPN, carrying the ferric citrate transport (FEC) system. We observed increasing FDC MICs in an Escherichia coli model system carrying different natural pKpQIL plasmids, encoding different K. pneumoniae carbapenemase (KPC) variants, in combination with a conjugative low copy number vector carrying the fec gene cluster from pKPN. We observed transcriptional repression of fiu, cirA, fepA, and fhuA siderophore receptor genes in bla-fec-E. coli cells treated with ferric citrate. Screening of 27,793 K. pneumoniae whole-genome sequences revealed that the fec cluster occurs frequently in some globally distributed different KPC-producing K. pneumoniae clones (sequence types 258, 14, 45, and 512), contributing to reduced FDC susceptibility.
头孢地尔（FDC）是一种铁载体-头孢菌素缀合物，是治疗耐碳青霉烯革兰氏阴性菌感染的最新选择。我们发现了一种导致肺炎克雷伯菌临床分离株对FDC敏感性降低的新机制。该机制涉及两个共存质粒：携带碳青霉烯酶基因变体的pKpQIL和携带柠檬酸铁转运（FEC）系统的pKPN。我们在携带不同天然pKpQIL质粒（编码不同的肺炎克雷伯菌碳青霉烯酶（KPC）变体）的大肠杆菌模型系统中观察到FDC最低抑菌浓度（MIC）增加，该系统与携带来自pKPN的fec基因簇的接合型低拷贝数载体结合。我们观察到在用柠檬酸铁处理的bla-fec-大肠杆菌细胞中，fiu、cirA、fepA和fhuA铁载体受体基因的转录受到抑制。对27793个肺炎克雷伯菌全基因组序列的筛选显示，fec簇在一些全球分布的不同产KPC肺炎克雷伯菌克隆（序列类型258、14、45和512）中频繁出现，导致对FDC的敏感性降低。
