Institute for Medical Microbiology and Hygiene, Austrian Agency for Health and Food Safety, Vienna, Austria
EUPHEM Fellowship, European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.
J Clin Microbiol. 2021 Feb 18;59(3). doi: 10.1128/JCM.02529-20.
Diphtheria is a vaccine-preventable disease with a high potential for reemergence. One of its causative agents is , with some strains producing diphtheria toxin. From 2011 to 2019, 57 clinical strains were isolated in Austria, either from the respiratory tract or from skin infections. The aim of this study was to investigate the genetic diversity of these isolates using whole-genome sequencing. Isolates were characterized by genome-wide comparisons using single nucleotide polymorphism analysis or core genome multilocus sequence typing and by searching sequence data for antimicrobial resistance genes and genes involved in diphtheria toxin production. The genetic diversity among the isolates was high, with no clear distribution over time or place. isolates were separated from other strains and were strongly associated with respiratory infections (odds ratio [OR] = 57). Two clusters, limited in time and space, were identified. Almost 40% of strains carried resistance genes against tetracycline or sulfonamides, mostly from skin infections. Microbiological tests showed that 55% of isolates were resistant to penicillin but did not carry genes conferring β-lactam resistance. A diphtheria toxin gene with no nonsynonymous mutation was found in three isolates only. This study showed that sequencing can provide valuable information complementing routine microbiological and epidemiological investigations. It allowed us to identify unknown clusters, evaluate antimicrobial resistance more broadly, and support toxigenicity results obtained by PCR. For these reasons, surveillance could strongly benefit from the routine implementation of whole-genome sequencing.
白喉是一种具有高度重现风险的可通过疫苗预防的疾病。其病原体之一是 ，某些菌株会产生白喉毒素。从 2011 年到 2019 年，奥地利从呼吸道或皮肤感染中分离出了 57 株临床 株。本研究旨在使用全基因组测序来研究这些 分离株的遗传多样性。通过全基因组比较、单核苷酸多态性分析或核心基因组多位点序列分型对分离株进行特征描述，并通过搜索序列数据来寻找抗菌药物耐药基因和白喉毒素产生相关基因。分离株之间的遗传多样性很高，没有明显的时间或地点分布。 分离株与其他菌株分离，与呼吸道感染密切相关（比值比 [OR] = 57）。确定了两个时间和空间均有限的聚类。近 40%的菌株对四环素或磺胺类药物具有耐药性，主要来自皮肤感染。微生物学测试显示，55%的分离株对青霉素耐药，但不携带β-内酰胺类耐药基因。仅在 3 株分离株中发现了一个无非同义突变的白喉毒素基因。本研究表明，测序可以提供有价值的信息，补充常规微生物学和流行病学调查。它使我们能够识别未知的聚类，更广泛地评估抗菌药物耐药性，并支持通过 PCR 获得的毒力结果。出于这些原因，监测工作可以从常规实施全基因组测序中受益匪浅。
