{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:12:02Z","timestamp":1782450722345,"version":"3.54.5"},"reference-count":55,"publisher":"Microbiology Society","issue":"6","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,29]]},"abstract":"\n Introduction.<\/jats:bold> Combination of PCR and Elek testing to identify toxigenic corynebacteria has revealed organisms described as non-toxigenic toxin-gene bearing (NTTB) \n \n Corynebacterium diphtheriae<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> or \n \n C. ulcerans<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> (i.e. PCR tox<\/jats:italic> positive; Elek negative). These organisms carry part or all of tox<\/jats:italic>, but are unable to express diphtheria toxin (DT) and present a challenge to clinical and public health case management.<\/jats:p>\n \n Gap analysis\/Hypothesis.<\/jats:bold> 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.<\/jats:p>\n \n Aim.<\/jats:bold> To characterize a cluster of infections due to NTTB in a skin clinic and subsequent cases in two household contacts.<\/jats:p>\n \n Methodology.<\/jats:bold> Epidemiological and microbiological investigations were carried out according to existing national guidance at the time. Susceptibility testing used gradient strips. The tox<\/jats:italic> operon analysis and multi-locus sequence typing (MLST) was derived from whole-genome sequencing. Alignment of the tox<\/jats:italic> operon and phylogenetic analyses were performed using clustalW, mega<\/jats:sc>, the public core-genome MLST (cgMLST) scheme and an in-house bioinformatic single nucleotide polymorphism (SNP) typing pipeline.<\/jats:p>\n \n Results.<\/jats:bold> Isolates of NTTB \n \n C. diphtheriae<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> 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\u2009months later, and from two household contacts (cases 5 and 6) after a further 18\u2009months and 3.5 years, respectively. All eight strains were NTTB \n \n C. diphtheriae<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> biovar mitis, belonged to the same sequence type (ST-336) with the same deletion in tox<\/jats:italic>. Phylogenetic analysis showed relatively high diversity between the eight strains with 7\u2013199 SNP and 3\u2013109 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\u201370 with 28\u201338 cgMLST loci differences.<\/jats:p>\n \n Conclusions.<\/jats:bold> We report a cluster of NTTB \n \n C. diphtheriae<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> cases in a skin clinic and evidence of onward household transmission. We conclude the deletion in the tox<\/jats:italic> 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.<\/jats:p>","DOI":"10.1099\/jmm.0.001722","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T16:16:38Z","timestamp":1688055398000},"source":"Crossref","is-referenced-by-count":7,"title":["Household transmission of non-toxigenic diphtheria toxin gene-bearing Corynebacterium diphtheriae following a cluster of cutaneous cases in a specialist outpatient setting"],"prefix":"10.1099","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4862-6507","authenticated-orcid":false,"given":"Norman K.","family":"Fry","sequence":"first","affiliation":[{"name":"Respiratory and Vaccine Preventable Bacteria Reference Unit, UK Health Security Agency, London, NW9 5EQ, UK"},{"name":"Immunisation and Vaccine Preventable Diseases Division, UK Health Security Agency, London, NW9 5EQ, 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