scholarly journals Corynebacterium diphtheriae: Diphtheria Toxin, the tox Operon, and Its Regulation by Fe2+ Activation of apo-DtxR

2019 ◽  
Vol 7 (4) ◽  
Author(s):  
Sadiya Parveen ◽  
William R. Bishai ◽  
John R. Murphy
Keyword(s):  
Diphtheria Toxin ◽  
Corynebacterium Diphtheriae

scholarly journals Induction and Resuscitation of Viable but Nonculturable Corynebacterium diphtheriae

2021 ◽  
Vol 9 (5) ◽  
pp. 927
Author(s):  
Takashi Hamabata ◽  
Mitsutoshi Senoh ◽  
Masaaki Iwaki ◽  
Ayae Nishiyama ◽  
Akihiko Yamamoto ◽  
...  
Keyword(s):  
Low Temperatures ◽  
Diphtheria Toxin ◽  
Pathogenic Bacteria ◽  
Corynebacterium Diphtheriae ◽  
Human Pathogen ◽  
Vbnc State ◽  
Viable But Nonculturable ◽  
Environmental Survival ◽  
Reverse Transcription Quantitative Pcr ◽  
Morphological Differences

Many pathogenic bacteria, including Escherichia coli and Vibrio cholerae, can become viable but nonculturable (VBNC) following exposure to specific stress conditions. Corynebacterium diphtheriae, a known human pathogen causing diphtheria, has not previously been shown to enter the VBNC state. Here, we report that C. diphtheriae can become VBNC when exposed to low temperatures. Morphological differences in culturable and VBNC C. diphtheriae were examined using scanning electron microscopy. Culturable cells presented with a typical rod-shape, whereas VBNC cells showed a distorted shape with an expanded center. Cells could be transitioned from VBNC to culturable following treatment with catalase. This was further evaluated via RNA sequence-based transcriptomic analysis and reverse-transcription quantitative PCR of culturable, VBNC, and resuscitated VBNC cells following catalase treatment. As expected, many genes showed different behavior by resuscitation. The expression of both the diphtheria toxin and the repressor of diphtheria toxin genes remained largely unchanged under all four conditions (culturable, VBNC, VBNC after the addition of catalase, and resuscitated cells). This is the first study to demonstrate that C. diphtheriae can enter a VBNC state and that it can be rescued from this state via the addition of catalase. This study helps to expand our general understanding of VBNC, the pathogenicity of VBNC C. diphtheriae, and its environmental survival strategy.

scholarly journals Diphtheria in two pregnant in the context of the epidemic in Venezuela

2021 ◽  
Vol 129 (3) ◽  
Author(s):  
Ana Carvajal ◽  
Silvana Vielma ◽  
Carballo Martín ◽  
Pedro José Quijada ◽  
José Manuel Barboza ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Diphtheria Toxin ◽  
Human Subjects ◽  
Corynebacterium Diphtheriae ◽  
Acute Infectious Disease

Diphtheria is an acute infectious disease caused by the bacterium Corynebacterium diphtheriae that encodes diphtheria toxin (DT) in susceptible human subjects during an outbreak. Venezuela has experienced a widespread resurgence of diphtheria since early 2016.

scholarly journals Population genomics and antimicrobial resistance in Corynebacterium diphtheriae

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Melanie Hennart ◽  
Leonardo G. Panunzi ◽  
Carla Rodrigues ◽  
Quentin Gaday ◽  
Sarah L. Baines ◽  
...  
Keyword(s):  
Soviet Union ◽  
Antimicrobial Resistance ◽  
Diphtheria Toxin ◽  
Population Genomics ◽  
Bacterial Species ◽  
Toxin Production ◽  
Multidrug Resistant ◽  
Corynebacterium Diphtheriae ◽  
Toxin Gene ◽  
Phylogenetic Structure

Abstract Background Corynebacterium diphtheriae, the agent of diphtheria, is a genetically diverse bacterial species. Although antimicrobial resistance has emerged against several drugs including first-line penicillin, the genomic determinants and population dynamics of resistance are largely unknown for this neglected human pathogen. Methods Here, we analyzed the associations of antimicrobial susceptibility phenotypes, diphtheria toxin production, and genomic features in C. diphtheriae. We used 247 strains collected over several decades in multiple world regions, including the 163 clinical isolates collected prospectively from 2008 to 2017 in France mainland and overseas territories. Results Phylogenetic analysis revealed multiple deep-branching sublineages, grouped into a Mitis lineage strongly associated with diphtheria toxin production and a largely toxin gene-negative Gravis lineage with few toxin-producing isolates including the 1990s ex-Soviet Union outbreak strain. The distribution of susceptibility phenotypes allowed proposing ecological cutoffs for most of the 19 agents tested, thereby defining acquired antimicrobial resistance. Penicillin resistance was found in 17.2% of prospective isolates. Seventeen (10.4%) prospective isolates were multidrug-resistant (≥ 3 antimicrobial categories), including four isolates resistant to penicillin and macrolides. Homologous recombination was frequent (r/m = 5), and horizontal gene transfer contributed to the emergence of antimicrobial resistance in multiple sublineages. Genome-wide association mapping uncovered genetic factors of resistance, including an accessory penicillin-binding protein (PBP2m) located in diverse genomic contexts. Gene pbp2m is widespread in other Corynebacterium species, and its expression in C. glutamicum demonstrated its effect against several beta-lactams. A novel 73-kb C. diphtheriae multiresistance plasmid was discovered. Conclusions This work uncovers the dynamics of antimicrobial resistance in C. diphtheriae in the context of phylogenetic structure, biovar, and diphtheria toxin production and provides a blueprint to analyze re-emerging diphtheria.

scholarly journals Assessing the Genetic Diversity of Austrian Corynebacterium diphtheriae Clinical Isolates, 2011-2019

2020 ◽  
Author(s):  
Justine Schaeffer ◽  
Steliana Huhulescu ◽  
Anna Stoeger ◽  
Franz Allerberger ◽  
Werner Ruppitsch
Keyword(s):  
Genetic Diversity ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Resistance Genes ◽  
Diphtheria Toxin ◽  
Corynebacterium Diphtheriae ◽  
Toxin Gene ◽  
Whole Genome ◽  
Skin Infections ◽  
Antimicrobial Resistance Genes

Background: Diphtheria is a vaccine preventable disease with a high potential for re-emergence. One of its causative agent is Corynebacterium diphtheriae, some strains producing the diphtheria toxin. From 2011 to 2019, 57 clinical C. diphtheriae strains were isolated in Austria, either from the respiratory track or from skin infections. Objectives: The aim of the study was to investigate the genetic diversity of these C. diphtheriae isolates using whole genome sequencing. Methods: Isolates were characterized by genome wide comparison using single nucleotide polymorphism or core genome multilocus sequence typing, and by searching sequence data for antimicrobial resistance genes and genes involved in diphtheria toxin production. Results: Genetic diversity between the isolates was high, with no clear distribution over time or place. C. belfantii isolates were separated from other strains, and were strongly associated with respiratory infections (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. Diphtheria toxin gene with no non-synonymous mutation was found in three isolates only. Conclusion: This study showed that sequencing can provide valuable information complementing routine microbiological and epidemiological investigations. It allowed us to identify unknown clusters, evaluate antimicrobial resistances more broadly and support toxigenicity results obtained by PCR. For these reasons, C. diphtheriae surveillance could strongly benefit from the routine implementation of whole genome sequencing.

scholarly journals Construction and Characterization of Transposon Insertion Mutations in Corynebacterium diphtheriae That Affect Expression of the Diphtheria Toxin Repressor (DtxR)

2002 ◽  
Vol 184 (20) ◽  
pp. 5723-5732 ◽  
Author(s):  
Diana Marra Oram ◽  
Ana Avdalovic ◽  
Randall K. Holmes
Keyword(s):  
Oxidative Stress ◽  
Diphtheria Toxin ◽  
Corynebacterium Diphtheriae ◽  
Insertion Mutant ◽  
Toxin Gene ◽  
Wild Type ◽  
Transposon Insertion ◽  
Diphtheria Toxin Repressor ◽  
Mutant Strains

ABSTRACT Transcription of the bacteriophage-borne diphtheria toxin gene tox is negatively regulated, in response to intracellular Fe2+ concentration, by the chromosomally encoded diphtheria toxin repressor (DtxR). Due to a scarcity of tools, genetic analysis of Corynebacterium diphtheriae has primarily relied on analysis of chemically induced and spontaneously occurring mutants and on the results of experiments with C. diphtheriae genes cloned in Escherichia coli or analyzed in vitro. We modified a Tn5-based mutagenesis technique for use with C. diphtheriae, and we used it to construct the first transposon insertion libraries in the chromosome of this gram-positive pathogen. We isolated two insertions that affected expression of DtxR, one 121 bp upstream of dtxR and the other within an essential region of the dtxR coding sequence, indicating for the first time that dtxR is a dispensable gene in C. diphtheriae. Both mutant strains secrete diphtheria toxin when grown in medium containing sufficient iron to repress secretion of diphtheria toxin by wild-type C. diphtheriae. The upstream insertion mutant still produces DtxR in decreased amounts and regulates siderophore secretion in response to iron in a manner similar to its wild-type parent. The mutant containing the transposon insertion within dtxR does not produce DtxR and overproduces siderophore in the presence of iron. Differences in the ability of the two mutant strains to survive oxidative stress also indicated that the upstream insertion retained slight DtxR activity, whereas the insertion within dtxR abolished DtxR activity. This is the first evidence that DtxR plays a role in protecting the cell from oxidative stress.

Corynebacterium hindlerae sp. nov., derived from a human granuloma, which forms black colonies and black halos on modified Tinsdale medium but is not closely related to Corynebacterium diphtheriae and related taxa

2021 ◽  
Vol 71 (8) ◽  
Author(s):  
Kathryn A. Bernard ◽  
Tamara Burdz ◽  
Ana Luisa Pacheco ◽  
Deborah Wiebe ◽  
Anne-Marie Bernier
Keyword(s):  
Diphtheria Toxin ◽  
Type Species ◽  
Corynebacterium Diphtheriae ◽  
Contact Tracing ◽  
Public Health Response ◽  
Potassium Tellurite ◽  
Content Type ◽  
Link Type ◽  
Corynebacterium Ulcerans ◽  
Health Response

Corynebacterium diphtheriae , Corynebacterium belfantii , Corynebacterium rouxii , Corynebacterium ulcerans , Corynebacterium pseudotuberculosis and Corynebacterium silvaticum are the only taxa from among ~121 Corynebacterium species deemed potentially able to harbour diphtheria tox genes. Subsequently tox-gene bearing species may potentially produce diphtheria toxin, which is linked to fatal respiratory distress if a pharyngeal pseudomembrane is formed or toxaemia develops in those unimmunized or under-immunized. Detection of diphtheria toxin-producing species may also invoke a public health response and contact tracing. Recovery of such species from the respiratory tract or other contaminated sources such as non-healing ulcerative wounds are expedited by use of differential and selective media such as modified Tinsdale medium (MTM). This medium is supplemented with potassium tellurite, which supresses most normal flora present in contaminated specimens, as well as l-cystine and thiosulphate. Most diphtheria-tox-gene bearing species grow well on MTM, producing black colonies with a black halo around each colony. This is due to an ability to produce cystinase in the presence of tellurite, cystine and thiosulphate, resulting in black tellurium deposits being observed in the agar. Other Corynebacterium species may/may not be able to grow at all in the presence of tellurite but if able to grow, will have small beige or brownish colonies which do not exhibit black halos. We describe here an unusual non-tox-gene-bearing isolate, NML 93-0612T, recovered from a human wrist granuloma, which produced black colonies with black halos on MTM agar but was otherwise distinguishable from Corynebacterium species which can bear tox genes. Distinctive features included its unusual colony morphology on MTM and sheep blood agar, by proteomic, biochemical and chemotaxonomic properties and by molecular methods. Its genome contained 2 680 694 bytes, a G+C content of 60.65 mol% with features consistent with the genus Corynebacterium and so represents a new species for which we propose the name Corynebacterium hindlerae sp. nov.

scholarly journals Respiratory Illness Caused by Corynebacterium diphtheriae and C. ulcerans, and Use of Diphtheria Antitoxin in the United States, 1996–2018

2020 ◽  
Author(s):  
John O Otshudiema ◽  
Anna M Acosta ◽  
Pamela K Cassiday ◽  
Stephen C Hadler ◽  
Susan Hariri ◽  
...  
Keyword(s):  
United States ◽  
Diphtheria Toxin ◽  
Healthcare Providers ◽  
Respiratory Illness ◽  
The United States ◽  
Corynebacterium Diphtheriae ◽  
Toxin Gene ◽  
Corynebacterium Ulcerans ◽  
Diphtheria Antitoxin ◽  
Control And Prevention

Abstract Background Respiratory diphtheria is a toxin-mediated disease caused by Corynebacterium diphtheriae. Diphtheria-like illness, clinically indistinguishable from diphtheria, is caused by Corynebacterium ulcerans, a zoonotic bacterium that can also produce diphtheria toxin. In the United States, respiratory diphtheria is nationally notifiable: specimens from suspected cases are submitted to the Centers for Disease Control and Prevention (CDC) for species and toxin confirmation, and diphtheria antitoxin (DAT) is obtained from CDC for treatment. We summarize the epidemiology of respiratory diphtheria and diphtheria-like illness and describe DAT use during 1996–2018 in the United States. Methods We described respiratory diphtheria cases reported to the National Notifiable Diseases Surveillance System (NNDSS) and C. ulcerans-related diphtheria-like illness identified through specimen submissions to CDC during 1996–2018. We reviewed DAT requests from 1997 to 2018. Results From 1996 to 2018, 14 respiratory diphtheria cases were reported to NNDSS. Among these 14 cases, 1 was toxigenic and 3 were nontoxigenic C. diphtheriae by culture and Elek, 6 were culture-negative but polymerase chain reaction (PCR)-positive for diphtheria toxin gene, 1 was culture-positive without further testing, and the remaining 3 were either not tested or tested negative. Five cases of respiratory diphtheria-like illness caused by toxigenic C. ulcerans were identified. DAT was requested by healthcare providers for 151 suspected diphtheria cases between 1997 and 2018, with an average of 11 requests per year from 1997 to 2007, and 3 per year from 2008 to 2018. Conclusions Respiratory diphtheria remains rare in the United States, and requests for DAT have declined. Incidental identification of C. ulcerans-related diphtheria-like illness suggests surveillance of this condition might be warranted.

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