Search Results (39)

Background: Diphtheria is an acute infectious disease caused by Corynebacterium diphtheriae. Despite several worldwide outbreaks, it is now considered a rare disease by industrialized countries. Clinical manifestations usually account for oropharyngeal lesions, but rare cases of systemic involvement (mainly endocarditis) have been described among non-toxigenic strains. Case description: We report the case of a patient who experienced septic shock, disseminated intravascular coagulation and multiorgan failure due to Corynebacterium diphtheriae infection. The pathogen was further characterized as a highly toxigenic strain. Infective endocarditis with mitral and aortic valve vegetations led to early multiorgan septic embolization. Major stroke, liver function impairment, heart failure and acute kidney injury were the main findings. Unlike the typical forms of infection caused by this pathogen, there was no evidence of airway or skin involvement. Furthermore, apart from hemocultures, none of the other investigations (pharyngeal swabs, bronchoalveolar lavages, urine culture) ever tested positive for the bacteria. Conclusions: The report we present describes a case of C. diphtheriae infection with many atypical characteristics: (i) lack of any pathognomonic signs or symptoms; (ii) extensive endocarditic process (very uncommon for toxigenic strains); (iii) early septic emboli development, with rapid evolution to multiorgan failure; (iv) detection of disseminated intravascular coagulation. Despite disseminated intravascular coagulation being a known complication of septic shock, regardless of the etiological agent, according to our literature research, this is the second known case driven by C. diphtheriae infection in an adult. Full article

Background and Clinical Significance: Corynebacterium striatum is an emerging multidrug-resistant pathogen increasingly implicated in infections among immunocompromised patients and patients with indwelling medical devices. Case Presentation: We report the probable first case of pseudomembranous inflammation associated with C. striatum infection in a 53-year-old male with an implanted left ventricular assist device (LVAD) awaiting heart transplantation. The patient experienced recurrent episodes of C. striatum bacteremia despite multiple courses of targeted antibiotic therapy, including vancomycin, linezolid, tedizolid, teicoplanin, and dalbavancin. During urgent heart transplantation, pseudomembranous tissue surrounding the LVAD driveline was observed, and cultures confirmed C. striatum device infection. Histopathological analysis revealed necrotic elements and Gram-positive organisms consistent with pseudomembranous inflammation. Conclusions: The case describes the diagnosis and treatment of this rare infection, highlighting the pathogenic potential of C. striatum, its role in device-related infections, and the histopathological evidence of pseudomembrane formation. Full article

Background: Corynebacterium ulcerans is an emerging zoonotic pathogen capable of cau-sing diphtheria-like infections in humans. Objectives: we report, for the first time in Brazil, the detection and phenotypic/genomic characterization of three atoxigenic ST-339 strains isolated from domestic animals, including one with a ciprofloxacin resistance profile linked to double GyrA mutations (S89L, D93G). Methods: species identification was performed by MALDI-TOF MS, followed by in vitro antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analyses to predict virulence determinants, antimicrobial resistance genes, CRISPR–Cas systems, mobile genetic elements, and in silico structural analysis as well as phylogenetic reconstruction. Results: whole-genome sequencing confirmed species identity, revealed high genetic similarity, and identified distinct phylogenetic subclades, suggesting potential international dissemination. Genomic analyses showed conserved virulence determinants, such as incomplete pilus clusters, iron acquisition systems, and the pld gene, with the absence of the tox gene. Molecular modeling and dynamics simulations indicated that GyrA mutations disrupt critical ciprofloxacin–magnesium–water interactions, reducing binding stability. Mobile genetic elements, prophages, and CRISPR–Cas systems underscored the genomic plasticity of these isolates. Conclusions: these findings document a little-studied antimicrobial resistance mechanism in zoonotic C. ulcerans, highlighting the need for strengthened surveillance and further research on virulence and resistance, even in ato-xigenic strains. Full article

Infectious diseases poses a growing public health challenge. The COVID-19 pandemic has further emphasized the urgent need for rapid, accessible diagnostics. This study presents the development of an integrated, flexible point-of-care (POC) diagnostic system for the rapid detection of Corynebacterium diphtheriae, the pathogen responsible for diphtheria. The system comprises a microfluidic polymerase chain reaction (micro-PCR) device and an electrochemical DNA biosensor, both fabricated on flexible substrates. The micro-PCR platform offers rapid DNA amplification overcoming the time limitations of conventional thermocyclers. The biosensor utilizes specific molecular recognition and an electrochemical transducer to detect the amplified DNA fragment, providing a clear and direct indication of the pathogen’s presence. The combined system demonstrates the effective amplification and detection of a gene fragment from a toxic strain of C. diphtheriae, chosen due to its increasing incidence. The design leverages lab-on-a-chip (LOC) and microfluidic technologies to minimize reagent use, reduce cost, and support portability. Key challenges in microsystem design—such as flow control, material selection, and reagent compatibility—were addressed through optimized fabrication techniques and system integration. This work highlights the feasibility of using flexible, integrated microfluidic and biosensor platforms for the rapid, on-site detection of infectious agents. The modular and scalable nature of the system suggests potential for adaptation to a wide range of pathogens, supporting broader applications in global health diagnostics. The approach provides a promising foundation for next-generation POC diagnostic tools. Full article

Diphtheria is a severely infectious and deadly bacterial disease with Corynebacterium diphtheriae as the causative agent. Since the COVID-19 pandemic, contagious diseases such as diphtheria have re-emerged due to disruptions in routine childhood immunization programs worldwide. Nigeria is witnessing a significant increase in diphtheria outbreaks likely due to an inadequate health care system and insufficient public enlightenment campaign. This paper presents a mathematical epidemic diphtheria model in Nigeria, which includes a public enlightenment campaign to assess its positive impact on the prevalence of the disease. The mathematical analysis of the model reveals two equilibrium points: the diphtheria infection-free equilibrium and the endemic equilibrium. These equilibrium points are shown to be stable globally asymptotically if ${\mathcal{R}}_c<1$ and ${\mathcal{R}}_c>1$, respectively. The model was fit using the confirmed diphtheria cases data of Kano State from January to December 2023. Sensitivity analysis indicates that the transmission rate and recovery rate of asymptomatic peopleare crucial parameters to be considered in developing effective strategies for diphtheria control and prevention. This analysis also reveals that the implementation of a high-level public enlightenment campaign and its high efficacy effectively reduce the prevalence of diphtheria. Finally, numerical simulations show that combining the public enlightenment campaign and isolating infected individuals is the best strategy to contain the spread of diphtheria. Full article

Background/Objectives: Despite a significant reduction in diphtheria incidence and mortality due to vaccination, antitoxin therapy and antibiotic treatments, a concerning resurgence is occurring in Europe. Resistance to penicillins and macrolides is emerging, resulting in a growing challenge for diphtheria management. This retrospective study aims to evaluate and compare antibiotic susceptibilities of both toxigenic Corynebacterium diphtheriae and C. ulcerans. Methods: Susceptibilities were assessed using broth microdilution—the gold standard—disk diffusion and the gradient method, and analyzed on the basis of the EUCAST breakpoint tables for the interpretation of MICs and zone diameters. Antimicrobial resistance genes and mutations were detected by analyzing whole-genome sequences (WGS). Results: A small number of C. diphtheriae isolates were resistant to the first-choice antimicrobial classes, penicillins and macrolides, while higher resistance rates were observed for ciprofloxacin (29%), tetracycline (38%) and trimethoprim-sulfamethoxazole (SXT, 85%). A good correlation was found with resistance genes and mutations detected by WGS. C. ulcerans isolates were susceptible to all tested antibiotics, except clindamycin, to which this species is naturally resistant, and a few ciprofloxacin resistances not confirmed by WGS. Diffusion techniques were found to be acceptable alternatives, but false susceptible results were detected for ciprofloxacin and tetracycline by disk diffusion and ciprofloxacin and SXT by gradient diffusion. Conclusions: Penicillins and macrolides remain the first-choice antibiotics for the treatment of diphtheria. However, antimicrobial susceptibility testing is needed for all toxigenic C. diphtheriae and C. ulcerans isolates, as resistance is emerging. Antimicrobial susceptibility testing should not be limited to penicillins and macrolides, but be extended to other antibiotics. When WGS is performed for epidemiological purposes, resistance genes and mutations should be looked for. Full article

Some Corynebacterium strains produce toxins that are similar to those produced by Corynebacterium diphtheriae, leading to human infections that are often transmitted through zoonotic diseases. A novel species, which is formerly classified as Corynebacterium ulcerans lineage II, was recently re-evaluated and renamed “Corynebacterium ramonii sp. nov.”. We isolated C. ramonii from a human skin ulcer in Japan in 2023 (KCU0303-001) and identified it as ST344 using a genomic analysis. In addition, C. ramonii KPHES-18084 (ST344) and six strains of C. ulcerans (ST337/ST1011) were isolated from the oral cavities of 7/208 rescued cats (3.4%). The human ulcer strain KCU0303-001 and the rescued cat strain KPHES-18084 were found to be ST344 and closely related clones by core-genome and pan-genome analyses, suggesting that ST344 may be endemic to both clinical and companion animals in Japan. In support of this finding, another clinical isolate of ST344 (TSU-28 strain) was reported in Japan in 2019. Although ST337 is the most common C. ulcerans infection, the second most recent clinical isolate of C. ramonii, ST344, might be increasing; therefore, further genomic surveillance is required to monitor C. ramonii and C. ulcerans infections. Full article

WHO (World Health Organization) reports from recent years warn about the growing number of antibiotic-resistant bacterial strains. Therefore, there is an urgent need to constantly search for new substances effective in the fight against microorganisms. Plants are a rich source of chemical compounds with antibacterial properties. These compounds, classified as secondary metabolites, may act independently or support the action of currently used antibiotics. Due to the large number of metabolites isolated from the plant kingdom and new plant species being studied, there is a need to develop new strategies/techniques or modifications of currently applied methods that can be used to select plant extracts or chemical compounds isolated from them that enter into positive, synergistic interactions with currently used antibiotics. One such method is the dual-disk synergy test (DDST). It involves the diffusion of active compounds in the agar environment and influencing the growth of microorganisms grown on it. The method was used to assess the interaction of extracts from the fruit and shoots of some cultivated varieties of Rubus idaeus and Rubus occidentalis with selected antibiotics. The research was conducted on strains of bacteria pathogenic to humans, including Staphylococcus aureus, Corynebacterium diphtheriae, Escherichia coli, Pseudomonas aeruginosa, Helicobacter pylori, and Candida albicans, showing synergy, antagonism, or lack of interaction of the tested substances—plant extract and antibiotic. As a result, it was found that the diffusion method is useful in screening tests to assess the impact of antibiotic–herbal substance interactions on Gram-positive and Gram-negative microorganisms. Full article

Diphtheria, a potentially life-threatening infectious disease, is primarily caused by the bacterium Corynebacterium diphtheriae. This pathogen induces a range of severe symptoms, including respiratory distress, cardiac arrhythmias, and, in extreme cases, fatal outcomes. This paper aim to unravel the transmission dynamics of diphtheria infection within the Caputo fractional derivatives framework, establishing the solutions’ existence and uniqueness. Through forward normalized sensitivity analysis, we scrutinize the key parameters influencing the basic reproduction number, a pivotal metric in understanding and controlling the spread of the disease. The results indicate that reducing the values of the interaction rate, transmission rate, and birth rate plays a key role in curtailing diphtheria transmission. Furthermore, employing an effective numerical tool, we present graphical representations that delineate the influence of various crucial model parameters on infection dynamics. Full article

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. Full article

Corynebacterium rouxii is one of the recently described species of the Corynebacterium diphtheriae complex. As this species can potentially infect different hosts and harbor the tox gene, producing diphtheria toxin, we present its first pangenomic analysis in this work. A total of fifteen genomes deposited in online databases were included. After confirming the taxonomic position of the isolates by genomic taxonomy, the genomes were submitted to genomic plasticity, gene synteny, and pangenome prediction analyses. In addition, virulence and antimicrobial resistance genes were investigated. Finally, epidemiological data were obtained through molecular typing, clustering, and phylogenetic analysis. Our data demonstrated genetic diversity within the species with low synteny. However, the gene content is extensively conserved, and the pangenome is composed of 2606 gene families, of which 1916 are in the core genome and 80 are related to unique genes. Prophages, insertion sequences, and genomic islands were found. A type I-E CRISPR-Cas system was also detected. Besides the tox gene, determinants involved in adhesion and iron acquisition and two putative antimicrobial resistance genes were predicted. These findings provide valuable insight about this species’ pathogenicity, evolution, and diversity. In the future, our data can contribute to different areas, including vaccinology and epidemiology. Full article

A seroepidemiological study was conducted in 2018 to assess diphtheria and tetanus antibodies in Guangzhou, China. Diphtheria and tetanus antibody concentrations were measured with an enzyme-linked immunosorbent assay. A total of 715 subjects were enrolled in the study. The overall diphtheria and tetanus toxoid IgG-specific antibody levels were 0.126 IU/mL (95% CI: 0.115, 0.137) and 0.210 IU/mL (95% CI: 0.185, 0.240), respectively; the overall positivity rate was 61.82% (95% CI: 58.14, 65.39) and 71.61% (95% CI: 68.3, 74.92), respectively. The diphtheria and tetanus antibody concentration was decreased by age and increased by doses. The geometric mean concentrations and positivity rate of diphtheria and tetanus antibodies were lowest and below the essential protection level in people over 14 years of age. Compared to children and adolescents, middle-aged people and the aged are at much higher risk of infection with Corynebacterium diphtheriae and Clostridium tetani. The current diphtheria and tetanus immunization schedule does not provide persistent protection after childhood. There is an urgent need to adjust the current immunization schedule. Full article

The pharmaceutical industry usually utilizes either hydrophobic or hydrophilic substances extracted from raw plant materials to prepare a final product. However, the waste products from the plant material still contain biologically active components with the opposite solubility. The aim of this study was to enhance the comprehensive usability of plant materials by developing a new no-waste extraction method for eucalypt leaves and by investigating the phytochemical and pharmacological properties of eucalypt extracts and their 3D-printed dosage forms. The present extraction method enabled us to prepare both hydrophobic soft extracts and hydrophilic (aqueous) dry extracts. We identified a total of 28 terpenes in the hydrophobic soft extract. In the hydrophilic dry extract, a total of 57 substances were identified, and 26 of them were successfully isolated. The eucalypt extracts studied showed significant antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Corynebacterium diphtheriae gravis, and Corynebacterium diphtheriae mitis. The anti-inflammatory activity of the dry extract was studied using a formalin-induced-edema model in mice. The maximum anti-exudative effect of the dry extract was 61.5% at a dose of 20 mg/kg. Composite gels of polyethylene oxide (PEO) and eucalypt extract were developed, and the key process parameters for semi-solid extrusion (SSE) 3D printing of such gels were verified. The SSE 3D-printed preparations of novel synergistically acting eucalypt extracts could have uses in antimicrobial and anti-inflammatory medicinal applications. Full article

This study aimed to evaluate the antibacterial, leishmanicidal, and cytotoxic potential of metabolites produced by bacteria isolated from rhizosphere soil samples. The bacterium was identified by genome sequencing as Streptomyces kronopolitis. A preliminary screening was carried out for the antimicrobial activity of S. kronopolitis, demonstrating activity against Staphylococcus aureus ATCC 6538, Corynebacterium diphtheriae ATCC 27010, C. diphtheriae ATCC 27012, and Mycobacterium abscessus, with inhibition halos of sizes 25, 36, 29, and 33 mm, respectively. To obtain secondary metabolites, the bacteria were subjected to submerged fermentation, and the metabolites were extracted using the liquid–liquid method with ethyl acetate. There was a similar MIC for M. abscessus and the two strains of C. diphtherium, reaching a concentration of 12.5 µg/mL, while that of S. aureus was 0.048 µg/mL. Assays for leishmanicidal activity and cytotoxicity against HEp-2 cells and red blood cells were performed. The metabolite showed an IC₅₀ of 9.0 ± 0.9 µg/mL and CC₅₀ of 221.2 ± 7.0 µg/mL. This metabolite does not have hemolytic activity and is more selective for parasites than for mammalian cells, with a selectivity index of 24.6. Thus, the studied metabolite may be a strong candidate for the development of less toxic drugs to treat diseases caused by pathogens. Full article

Within the genus Corynebacterium, six species are potential carriers of the tox gene, which encodes the highly potent diphtheria exotoxin: Corynebacterium diphtheriae, Corynebacterium belfantii, Corynebacterium rouxii, Corynebacterium ulcerans, Corynebacterium pseudotuberculosis and Corynebacterium silvaticum. Based on their potential to infect different host species and cause either human infections, zoonotic diseases or infections of economically important animals, these bacteria are of high scientific and economic interest and different research groups have carried out proteome analyses. These showed that especially the combination of MS-based proteomics with bioinformatic tools helped significantly to elucidate the functional aspects of corynebacterial genomes and to handle the genome and proteome complexity. The combination of proteomic and bioinformatic approaches was also used to discover new vaccine and drug targets. In addition, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been established as a fast and precise tool for the identification of these bacteria. Full article