Arushothy Revathy, Bahari Norazlah, Manoharan Punitha, Mohd Ali Mohammad Ridhuan, Rosli Siti Nur Zawani, Samsuddin Nazirah, Che Unik Nur Sulhi Ilani, Amran Fairuz, Mohd Tap Ratna, Hashim Rohaidah, Nathan Sheila
Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam, Selangor, Malaysia; Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.
Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam, Selangor, Malaysia; Microbiology Unit, Department of Pathology, Hospital Selayang, Selangor, Malaysia.
Infect Genet Evol. 2025 Sep;133:105788. doi: 10.1016/j.meegid.2025.105788. Epub 2025 Jun 17.
Melioidosis, which is endemic in Malaysia, is caused by Burkholderia pseudomallei and has an elevated risk of mortality. This study reports a case of fatal melioidosis involving an adolescent, where the B. pseudomallei variant causing the infection was traced to the environment based on whole genome sequencing (WGS) analysis.
Burkholderia pseudomallei was isolated from an adolescent patient with no known risk factors, who developed fatal community-acquired pneumonia and sepsis. Further investigation and environment sampling were performed to identify the route of infection. Genomic characterization of both clinical and environmental B. pseudomallei isolates was performed to establish genetic relatedness, assess phylogenomic relationships, and identify virulence and antimicrobial resistance genes.
Genomic pairwise SNP distance analysis suggests a shared common ancestor between the patient and environmental isolates. Nevertheless, the identification of the novel sequence type ST1901 in both supports the hypothesis of environmental acquisition from a local source. Further analysis identified strain-specific genes that confirmed the strain's regional specificity and virulence. The patient succumbed to the infection despite the isolate being susceptible to the antimicrobials used for melioidosis, and the lack of correlation with antimicrobial resistance gene mutations suggests that treatment failure was not due to resistance. The fatal outcome may have resulted from a delay in initiating effective treatment, leading to the disease progression.
This study highlights the effectiveness of WGS in tracing B. pseudomallei infections, which could guide improved diagnostics to enhance melioidosis patient management and treatment outcomes.
类鼻疽在马来西亚为地方病，由类鼻疽伯克霍尔德菌引起，致死风险较高。本研究报告了一例涉及青少年的致命类鼻疽病例，通过全基因组测序（WGS）分析，追踪到引起感染的类鼻疽伯克霍尔德菌变种来源于环境。
从一名无已知风险因素、患致命社区获得性肺炎和败血症的青少年患者中分离出类鼻疽伯克霍尔德菌。进行了进一步调查和环境采样以确定感染途径。对临床和环境来源的类鼻疽伯克霍尔德菌分离株进行基因组特征分析，以建立遗传相关性、评估系统发育关系并鉴定毒力和抗微生物耐药基因。
基因组成对单核苷酸多态性（SNP）距离分析表明患者和环境分离株之间有共同的祖先。然而，两者中均鉴定出新型序列类型ST1901，这支持了从本地环境获得感染的假说。进一步分析确定了菌株特异性基因，证实了该菌株的区域特异性和毒力。尽管分离株对用于治疗类鼻疽的抗菌药物敏感，但患者仍死于感染，且与抗微生物耐药基因突变缺乏相关性，这表明治疗失败并非由于耐药。致命结局可能是由于开始有效治疗延迟，导致疾病进展。
本研究强调了WGS在追踪类鼻疽伯克霍尔德菌感染方面的有效性，这可为改进诊断提供指导以加强类鼻疽患者的管理和治疗效果。
