Immunisation and Vaccine Preventable Diseases Division, UK Health Security Agency, London, NW9 5EQ, UK.
Respiratory and Vaccine Preventable Bacteria Reference Unit, UK Health Security Agency, London, NW9 5EQ, UK.
J Med Microbiol. 2023 Jun;72(6). doi: 10.1099/jmm.0.001722.
Combination of PCR and Elek testing to identify toxigenic corynebacteria has revealed organisms described as non-toxigenic toxin-gene bearing (NTTB) or (i.e. PCR positive; Elek negative). These organisms carry part or all of , but are unable to express diphtheria toxin (DT) and present a challenge to clinical and public health case management. There are few data on the theoretical risk of NTTB reversion to toxigenicity. This unique cluster and subsequent epidemiologically linked isolates allowed the opportunity to determine any change in DT expression status. To characterize a cluster of infections due to NTTB in a skin clinic and subsequent cases in two household contacts. Epidemiological and microbiological investigations were carried out according to existing national guidance at the time. Susceptibility testing used gradient strips. The operon analysis and multi-locus sequence typing (MLST) was derived from whole-genome sequencing. Alignment of the operon and phylogenetic analyses were performed using clustalW, mega, the public core-genome MLST (cgMLST) scheme and an in-house bioinformatic single nucleotide polymorphism (SNP) typing pipeline. Isolates of NTTB were recovered from four cases (cases 1 to 4) with epidermolysis bullosa attending the clinic. Two further isolates were subsequently recovered from case 4, >18 months later, and from two household contacts (cases 5 and 6) after a further 18 months and 3.5 years, respectively. All eight strains were NTTB biovar mitis, belonged to the same sequence type (ST-336) with the same deletion in . Phylogenetic analysis showed relatively high diversity between the eight strains with 7-199 SNP and 3-109 cgMLST loci differences between them. The number of SNPs between the three isolates from case 4 and two household contacts (cases 5 and 6) was 44-70 with 28-38 cgMLST loci differences. We report a cluster of NTTB cases in a skin clinic and evidence of onward household transmission. We conclude the deletion in the was responsible for the non-expression of DT. There was no evidence of reversion to DT expression over the 6.5 year period studied. These data informed revision to guidance in the management of NTTB cases and their contacts in the UK.
聚合酶链反应（PCR）和 Elek 检测相结合，可鉴定产毒棒状杆菌，结果发现有些被描述为非产毒但带有毒素基因（NTTB）或（即 PCR 阳性；Elek 阴性）的生物体。这些生物体携带部分或全部，但无法表达白喉毒素（DT），给临床和公共卫生病例管理带来挑战。关于 NTTB 回复产毒性的理论风险的数据很少。这一独特的聚类和随后的流行病学相关分离株为确定 DT 表达状态的任何变化提供了机会。目的是确定皮肤诊所中由于 NTTB 引起的感染群集以及随后在两个家庭接触者中的病例。根据当时现有的国家指南进行了流行病学和微生物学调查。药敏试验采用梯度条。通过全基因组测序得出 操纵子分析和多位点序列分型（MLST）。使用 clustalW、mega、公共核心基因组 MLST（cgMLST）方案和内部生物信息单核苷酸多态性（SNP）分型管道对 操纵子进行比对和系统发育分析。从 4 例（病例 1 至 4）患有大疱性表皮松解症的患者中分离出 NTTB 。随后，在病例 4 中，在 >18 个月后，以及在病例 5 和 6 中，在另一个 18 个月和 3.5 年后，分别从病例 4 中分离出另外 2 株。所有 8 株均为 NTTB 生物型温和，属于相同的序列型（ST-336）， 中存在相同的缺失。系统发育分析显示，这 8 株之间的多样性相对较高，它们之间有 7-199 个 SNP 和 3-109 个 cgMLST 基因座差异。病例 4 中的 3 个分离株与两个家庭接触者（病例 5 和 6）之间的 SNP 数为 44-70，cgMLST 基因座差异为 28-38。我们报告了一个皮肤诊所中 NTTB 病例群集和家庭传播的证据。我们得出结论， 中的缺失导致 DT 无法表达。在研究的 6.5 年期间，没有证据表明 DT 表达恢复。这些数据为英国 NTTB 病例及其接触者的管理指南的修订提供了信息。
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