Point mutations sites in tox promoter/operator and diphtheria toxin repressor (DtxR) gene associated with the level of toxin production by Corynebacterium diphtheriae strains isolated in Belarus

Kolodkina, Valentina; Titov, L. P.; Sharapa, Tatyana; Drozhzhina, O. N.

doi:10.3103/s0891416807010041

Cited by 7 publications

(4 citation statements)

References 35 publications

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“…In diphtheria epidemic in Russia, it was found that base mutations at the tox operon in two of the 81 strains were not affecting the amino acid sequence of diphtheria toxin (Kolodkina et al 2007). The structural gene encoding diphtheria toxin, tox gene, is carried by corynebacteriophage but the regulation of the expression is maintained by the regulatory elements encoded by C. diphtheriae, namely dtxR.…”

Section: Introductionmentioning

confidence: 99%

Tengkawang cultivation model in community forest using agroforestry systems in West Kalimantan, Indonesia

et al. 2017

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Mulyastuti Y, Rahayu SI, Sunarno S, Santoso S, Wasito EB. 2017. Short Communication: Investigation of Diphtheria in Indonesia: dtxR and tox genes analysis of Corynebacterium diphtheriae collected from outbreaks. Biodiversitas 18: 784-787. Diphtheria outbreaks have sporadically occurred in Indonesia recently. It is suspected that toxin profile changes play an important role in vaccine efficacy and the occurrence of outbreaks. This study aimed to investigate the genetic changes of dtxR and tox genes in Corynebacterium diphtheria in Indonesia. Four C. diphtheriae toxigenic isolates circulating in current outbreak area were analyzed by comparing DNA sequences of their dtxR and tox genes to those of the PW8 vaccine strain. Among the four isolates, three point mutations were detected in dtxR gene while three other point mutations were detected in the tox gene. All six were silent mutations, suggesting that the diphtheria toxin is highly conserved at the amino acid sequence level, and indirectly indicating that the vaccine remains appropriate. Genetic variation in dtxR and tox genes of C. diphtheriae isolates from the recent outbreaks in Indonesia was detected.

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Section: Introductionmentioning

confidence: 99%

Tengkawang cultivation model in community forest using agroforestry systems in West Kalimantan, Indonesia

et al. 2017

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“…Variances of bacterial virulence that have been reported are mutations in the toxin promoter-operator region (tox PO) that affect toxin expression (19). The research of Kolodkina et al show that C. diphtheriae promoter/operator confirm that an increased level of toxin production by strains is determined by the mutation located in the 9-bp palindrome, which overlaps the -10 sequence of the promoter and the operator region (16).…”

Section: Discussionmentioning

confidence: 99%

“…Mutations and changes in the genetic structure of tox B allow the failure to recognize antibodies that cause diphtheria infection to persist even after vaccination (13)(14)(15). Mutations in the tox B gene can prevent the antitoxin from attaching and lead to failure of the neutralisation process, with eventual cell damage (16). It seems that complete vaccination does not guarantee protection against C. diphtheria infection.…”

Section: Introductionmentioning

confidence: 99%

Genetic characterization of diphtheria tox B to evaluate vaccine efficacy in Indonesia

Rosana

Lusiana

Yasmon

2022

IJM

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Background and Objectives: Blocking the attachment of diphtheria toxins to host cells through the intact receptor binding site (tox B) was the initial mechanism of action of the diphtheria vaccine. Diphtheria outbreaks in populations with good vaccination coverage can be caused by mutations or changes in the genetic structure of the tox B protein. The aim of this study was to characterize the Tox B protein produced by Corynebacterium diphtheriae isolated from 2018 to 2019 in patients in Jakarta who had already received the diphtheria vaccine. Materials and Methods: Of the 89 throat swab specimens of patients with a clinical diagnosis of diphtheria, 10 were posi- tive for diphtheria and toxin. PCR was used to amplify the tox B DNA fragment in the 10 positive isolates. DNA sequencing was conducted with overlapping primers and the DNA sequences were analysed by using SeqScape V2.7. Results: Of the 10 isolates, nine isolate showed a DNA mutation (G30A), but the mutation did not change the amino acid encoding arginin (silent mutation). Our findings indicate that the efficacy of the diphtheria vaccine used in Indonesia has not decreased because of mutations in the tox B genes not change the amino acid. Conclusion: Overall, there are no amino acid changes in the tox B protein, indicating that the outbreaks are not affected by mutation in tox B. Another possible mechanism – overexpression of the toxin – is likely responsible for causing diphtheria in patients who have a complete history of immunization in Indonesia.

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“…In consequence, the authors point to other factors that could have reduced the efficacy of the diphtheria vaccine used in Indonesia, for example, mutations in the toxin promoter/operator region ( tox PO) [ 99 ]. The results of the research by Kolodkina et al showed that the increase in the level of DT production is determined by the mutation located in the 9-bp palindrome, which overlaps the –10 sequence of the promoter and the operator region [ 104 ].…”

Section: Variations In the Nucleotide And Amino Acid Sequences Of Dtmentioning

confidence: 99%

Challenges of Diphtheria Toxin Detection

Prygiel,

Mosiej,

Polak

et al. 2024

Toxins

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Diphtheria toxin (DT) is the main virulence factor of Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Moreover, new Corynebacterium species with the potential to produce diphtheria toxin have also been described. Therefore, the detection of the toxin is the most important test in the microbiological diagnosis of diphtheria and other corynebacteria infections. Since the first demonstration in 1888 that DT is a major virulence factor of C. diphtheriae, responsible for the systemic manifestation of the disease, various methods for DT detection have been developed, but the diagnostic usefulness of most of them has not been confirmed on a sufficiently large group of samples. Despite substantial progress in the science and diagnostics of infectious diseases, the Elek test is still the basic recommended diagnostic test for DT detection. The challenge here is the poor availability of an antitoxin and declining experience even in reference laboratories due to the low prevalence of diphtheria in developed countries. However, recent and very promising assays have been developed with the potential for use as rapid point-of-care testing (POCT), such as ICS and LFIA for toxin detection, LAMP for tox gene detection, and biosensors for both.

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Point mutations sites in tox promoter/operator and diphtheria toxin repressor (DtxR) gene associated with the level of toxin production by Corynebacterium diphtheriae strains isolated in Belarus

Cited by 7 publications

References 35 publications

Tengkawang cultivation model in community forest using agroforestry systems in West Kalimantan, Indonesia

Tengkawang cultivation model in community forest using agroforestry systems in West Kalimantan, Indonesia

Genetic characterization of diphtheria tox B to evaluate vaccine efficacy in Indonesia

Challenges of Diphtheria Toxin Detection

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