Long Haiyan, Zhao Feifei, Feng Yu, Zong Zhiyong
Center of Infectious Diseases, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, China.
Center for Pathogen Research, West China Hospital, Sichuan University, Chengdu, China.
J Antimicrob Chemother. 2025 Jan 3;80(1):178-181. doi: 10.1093/jac/dkae393.
Escherichia coli producing metallo-β-lactamases with penicillin-binding protein 3 (PBP3) insertions have reduced susceptibility to aztreonam-avibactam and cefiderocol. Here, we analysed high-quality E. coli genomes for PBP3 insertions.
E. coli genomes (n = 167 518) were retrieved from EnteroBase with CheckM2 for quality control, fastANI for species confirmation, multi-locus sequencing typing for sequence type (ST) determination and AMRFinderPlus for resistance gene identification. For PBP3 insertion analysis, we used Prokka for predicting coding sequences, BLAST+ for comparing resulted protein sequences and SnpEff for annotating variants.
Among the included 159 341 genomes, PBP3 insertions with 11 variants were found in 2.01% (n = 3198). The predominant variant is a duplication of 334-337 amino acids (aa) (94.75%, n = 3030), comprising YRIN (65.92%, n = 2108) and its single-aa-variant YRIK (28.83%, n = 922), followed by a similar PYRI duplication of 333-336 (4.16%, n = 133). The less common ones are a TIPY duplication of 331-334 (n = 24) and its single-aa-variant TVPY's duplication: TVVPY (n = 1), TVPYTVPY (n = 1) and TVPYPVPY (n = 1). Rare duplications include VGDR of 106-109 (n = 3), ANALNIPL of 114-121 (n = 3), AL of 567-568 (n = 1) and TG of 584-585 (n = 1). Insertion variants were detected across 62 countries on six continents, primarily in human samples, and associated with 85 STs, concentrated in high-risk clones ST410 (29.18%, n = 1923), ST167 (23.40%, n = 1740) and ST405 (10.56%, n = 1334), with 83.32% (n = 2218) encoding metallo-β-lactamase NDM.
Global spread of E. coli harbouring PBP3 insertion, often with NDM β-lactamase, high-risk ST410, ST167 and ST405 clones and various hosts, underscores the escalating antimicrobial resistance crisis and the urgency for a 'One Health' strategy.
产生金属β-内酰胺酶且青霉素结合蛋白3（PBP3）插入的大肠埃希菌对氨曲南-阿维巴坦和头孢地尔的敏感性降低。在此，我们分析了高质量大肠埃希菌基因组中的PBP3插入情况。
从EnteroBase检索大肠埃希菌基因组（n = 167518），使用CheckM2进行质量控制，fastANI进行菌种确认，多位点测序分型确定序列类型（ST），并使用AMRFinderPlus鉴定耐药基因。对于PBP3插入分析，我们使用Prokka预测编码序列，BLAST+比较所得蛋白质序列，并使用SnpEff注释变异。
在所纳入的159341个基因组中，发现2.01%（n = 3198）存在11种变异的PBP3插入。主要变异是334 - 337个氨基酸（aa）的重复（94.75%，n = 3030），包括YRIN（65.92%，n = 2108）及其单氨基酸变异体YRIK（28.83%，n = 922），其次是333 - 336的类似PYRI重复（4.16%，n = 133）。较不常见的是331 - 334的TIPY重复（n = 24）及其单氨基酸变异体TVPY的重复：TVVPY（n = 1）、TVPYTVPY（n = 1）和TVPYPVPY（n = 1）。罕见重复包括106 - 109的VGDR（n = 3）、114 - 121的ANALNIPL（n = 3）、567 - 568的AL（n = 1）和584 - 585的TG（n = 1）。插入变异在六大洲的62个国家被检测到，主要存在于人类样本中，并与85种ST相关，集中在高危克隆ST410（29.18%，n = 1923）、ST167（23.40%，n = 1740）和ST405（10.56%，n = 1334），其中83.32%（n = 2218）编码金属β-内酰胺酶NDM。
携带PBP3插入（通常伴有NDMβ-内酰胺酶）、高危ST410、ST167和ST405克隆以及各种宿主类型的大肠埃希菌在全球范围内传播，凸显了抗菌药物耐药危机的不断升级以及“同一健康”战略的紧迫性。
