The global dissemination of carbapenemase genes, particularly , poses a significant threat to public health. While research has mainly focused on strains with phenotypic resistance, the impact of silent resistance genes has been largely overlooked. This study documents the first instance of silent in a cluster of clonally related carbapenem-susceptible strains from a single patient. Despite initial effectiveness of carbapenem therapy, the patient experienced four recurrent lung infections over five months, indicating persistent infection. Genomic sequencing revealed all strains harbored on the epidemic IncX3 plasmid. A deletion within the upstream promoter region (P) of hindered its expression, resulting in phenotypic susceptibility to carbapenems. However, in vitro bactericidal assays and a mouse infection model showed that strains with silent exhibited significant tolerance to carbapenem-mediated killing. These findings demonstrate that silent can mediate both phenotypic susceptibility and antibiotic tolerance. In silico analysis of 1986 sequences showed that 1956 (98.5%) retained the original promoter P. Given that previous genomic sequencing typically targets carbapenem-resistant strains, accurately assessing the prevalence of silent remains challenging. This study highlights the hidden threat of silent resistance genes to clinical antimicrobial therapy and calls for enhanced clinical awareness and laboratory detection.

中文翻译：

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碳青霉烯类肺炎克雷伯菌中沉默 NDM-1 碳青霉烯酶基因的出现：临床意义和流行病学见解


尤其是碳青霉烯酶基因的全球传播对公众健康构成了重大威胁。虽然研究主要集中在具有表型抗性的菌株上，但沉默抗性基因的影响在很大程度上被忽视了。这项研究记录了来自单个患者的克隆相关碳青霉烯类敏感菌株群中的第一个沉默实例。尽管碳青霉烯类治疗最初有效，但该患者在五个月内经历了四次反复肺部感染，表明持续感染。基因组测序揭示了流行性 IncX3 质粒上携带的所有菌株。上游启动子区 (P) 内的缺失阻碍了其表达，导致对碳青霉烯类药物的表型敏感性。然而，体外杀菌试验和小鼠感染模型表明，沉默菌株对碳青霉烯介导的杀伤表现出显着的耐受性。这些发现表明沉默可以介导表型敏感性和抗生素耐受性。对 1986 序列的计算机分析表明 1956 (98.5%) 保留了原始启动子 P。鉴于之前的基因组测序通常针对碳青霉烯类耐药菌株，准确评估沉默的流行率仍然具有挑战性。这项研究强调了沉默耐药基因对临床抗菌治疗的潜在威胁，并呼吁加强临床意识和实验室检测。