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急性髓系白血病:一项针对非急性髓系白血病分离株的比较基因组研究。

in Acute Myeloid Leukemia: A Comparative Genomic Study Against Non-AML Isolates.

作者信息

McMahon Stephanie, Franklin Samantha, Batool Maliha, Sadasivan Nitya, Fatima Safa, Galloway-Peña Jessica

机构信息

Laboratory of Jessica Galloway-Peña, Interdisciplinary Genetics Program, Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843, USA.

出版信息

Pathogens. 2025 Jun 24;14(7):627. doi: 10.3390/pathogens14070627.

Abstract

Bloodstream infections (BSIs) are a major cause of morbidity and mortality in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. , typically a skin commensal, is increasingly recognized as a pathogen in these vulnerable individuals. This study investigated whether genomic differences exist between infectious and gastrointestinal colonizing isolates from AML patients and how these compare to colonizing and infectious isolates from other patient groups and biogeographic sites. We analyzed 114 isolates-44 from AML patients (23 infections, 21 GI colonizers) and 70 from public datasets (34 infections, 36 colonizers). Stool samples underwent 16S rRNA sequencing and culture to identify colonization, while bloodstream isolates were sequenced and compared. Genomic profiling using Roary, Scoary, Phyre2, and InterProScan revealed that infectious and GI-colonizing AML isolates were phylogenetically close but genomically distinct. Infectious isolates from AML patients were significantly enriched for resistance genes (e.g., , , , ) and the biofilm-associated gene . AML infectious isolates harbored more resistance genes and mobile elements than non-AML strains but lacked widespread classical virulence factors. These results suggest that pathogenicity in immunocompromised hosts is driven by genomic adaptability and antibiotic tolerance rather than traditional virulence mechanisms.

摘要

血流感染(BSIs)是接受诱导化疗的急性髓系白血病(AML)患者发病和死亡的主要原因。 ,通常是一种皮肤共生菌,在这些易感个体中越来越被认为是一种病原体。本研究调查了AML患者的感染性分离株和胃肠道定植分离株之间是否存在基因组差异,以及这些差异与其他患者群体和生物地理位点的定植和感染分离株相比如何。我们分析了114株分离株——44株来自AML患者(23例感染,21例胃肠道定植菌),70株来自公共数据集(34例感染,36例定植菌)。对粪便样本进行16S rRNA测序和培养以确定定植情况,同时对血流分离株进行测序和比较。使用Roary、Scoary、Phyre2和InterProScan进行基因组分析表明,AML患者的感染性分离株和胃肠道定植分离株在系统发育上相近,但在基因组上有差异。AML患者的感染性分离株显著富集耐药基因(如 、 、 、 )和生物膜相关基因 。AML感染性分离株比非AML菌株含有更多的耐药基因和移动元件,但缺乏广泛存在的经典毒力因子。这些结果表明,在免疫受损宿主中的致病性是由基因组适应性和抗生素耐受性驱动的,而不是传统的毒力机制。

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