scholarly journals Oral Candidiasis: A Disease of Opportunity

2020 ◽  
Vol 6 (1) ◽  
pp. 15 ◽  
Author(s):  
Taissa Vila ◽  
Ahmed S. Sultan ◽  
Daniel Montelongo-Jauregui ◽  
Mary Ann Jabra-Rizk
Keyword(s):  
Immune Response ◽  
Oral Cavity ◽  
Oral Mucosa ◽  
Virulence Factors ◽  
Proteolytic Enzymes ◽  
Oral Candidiasis ◽  
Host Susceptibility ◽  
Initial Growth ◽  
Denture Stomatitis ◽  
Wide Range

Oral candidiasis, commonly referred to as “thrush,” is an opportunistic fungal infection that commonly affects the oral mucosa. The main causative agent, Candida albicans, is a highly versatile commensal organism that is well adapted to its human host; however, changes in the host microenvironment can promote the transition from one of commensalism to pathogen. This transition is heavily reliant on an impressive repertoire of virulence factors, most notably cell surface adhesins, proteolytic enzymes, morphologic switching, and the development of drug resistance. In the oral cavity, the co-adhesion of C. albicans with bacteria is crucial for its persistence, and a wide range of synergistic interactions with various oral species were described to enhance colonization in the host. As a frequent colonizer of the oral mucosa, the host immune response in the oral cavity is oriented toward a more tolerogenic state and, therefore, local innate immune defenses play a central role in maintaining Candida in its commensal state. Specifically, in addition to preventing Candida adherence to epithelial cells, saliva is enriched with anti-candidal peptides, considered to be part of the host innate immunity. The T helper 17 (Th17)-type adaptive immune response is mainly involved in mucosal host defenses, controlling initial growth of Candida and inhibiting subsequent tissue invasion. Animal models, most notably the mouse model of oropharyngeal candidiasis and the rat model of denture stomatitis, are instrumental in our understanding of Candida virulence factors and the factors leading to host susceptibility to infections. Given the continuing rise in development of resistance to the limited number of traditional antifungal agents, novel therapeutic strategies are directed toward identifying bioactive compounds that target pathogenic mechanisms to prevent C. albicans transition from harmless commensal to pathogen.

scholarly journals PREVENTION OF CANDIDIASIS IN PATIENTS USING REMOVABLE DENTURES

2022 ◽  
Author(s):  
Andrey SEVBITOV ◽  
◽  
Aleksey DOROFEEV ◽  
Sergey MIRONOV ◽  
Samer AL-KHOURY ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Oral Mucosa ◽  
Oral Candidiasis ◽  
Age Groups ◽  
Local Immunity ◽  
Thermal Insulating ◽  
Removable Plate ◽  
Orthopedic Care ◽  
Oral Tissue ◽  
Receptor Apparatus

Despite innovations in orthopedic dentistry, removable dentures belong to the most popular orthopedic care category. Removable dentures are combined stimuli that affect the mucous membrane and neuro-receptor apparatus. Acrylic plastic prostheses, widely used in prosthetic dentistry, have a negative side mechanical, chemical-toxic, sensitizing, and thermal insulating effect on oral tissue and prosthetic impression area. This is often complicated by a violation of the biocenosis of the oral cavity, the growth of pathogenic microflora that releases toxins, especially an increase in the number of yeast colonies that irritate the oral mucosa and prosthetic stomatitis. It was observed 100 patients with oral candidiasis of various age groups from 45 to 65 years. Of these, 60 patients with removable plate prostheses; 40 patients with partially removable prostheses. Chronic forms of candidiasis were diagnosed in 40 patients and with exacerbation of chronic forms of candidiasis in 60 people. The number of untreated carious cavities and poor hygienic condition of the oral cavity directly affects the severity of candidiasis. Acute forms of candidiasis were observed mainly in patients with high DMF and PMA indices. The severity of candidiasis depends on the degree and duration of wearing dentures and hygienic conditions - the most severe forms of invasive candidiasis were observed in the presence of removable plate prostheses, the complete absence of teeth, and the use of a prosthesis for more than 10-15 years. A combined lesion of the oral mucosa and the red border of the lips was observed mainly in patients older than 60 years. The presence of candidiasis in the oral cavity in patients with removable plate prostheses leads to a statistically significant change in the indicators of local immunity of the oral cavity: an increase in the concentration of serum IgG and IgA and the values of the coefficient of the balance of local immunity factors.

scholarly journals Candida albicans—The Virulence Factors and Clinical Manifestations of Infection

2021 ◽  
Vol 7 (2) ◽  
pp. 79
Author(s):  
Jasminka Talapko ◽  
Martina Juzbašić ◽  
Tatjana Matijević ◽  
Emina Pustijanac ◽  
Sanja Bekić ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Oral Candidiasis ◽  
Clinical Manifestations ◽  
The Body ◽  
Host Immune System ◽  
Normal Flora ◽  
Virulence Traits ◽  
Organ Systems ◽  
Wide Range

Candida albicans is a common commensal fungus that colonizes the oropharyngeal cavity, gastrointestinal and vaginal tract, and healthy individuals’ skin. In 50% of the population, C. albicans is part of the normal flora of the microbiota. The various clinical manifestations of Candida species range from localized, superficial mucocutaneous disorders to invasive diseases that involve multiple organ systems and are life-threatening. From systemic and local to hereditary and environmental, diverse factors lead to disturbances in Candida’s normal homeostasis, resulting in a transition from normal flora to pathogenic and opportunistic infections. The transition in the pathophysiology of the onset and progression of infection is also influenced by Candida’s virulence traits that lead to the development of candidiasis. Oral candidiasis has a wide range of clinical manifestations, divided into primary and secondary candidiasis. The main supply of C. albicans in the body is located in the gastrointestinal tract, and the development of infections occurs due to dysbiosis of the residential microbiota, immune dysfunction, and damage to the muco-intestinal barrier. The presence of C. albicans in the blood is associated with candidemia–invasive Candida infections. The commensal relationship exists as long as there is a balance between the host immune system and the virulence factors of C. albicans. This paper presents the virulence traits of Candida albicans and clinical manifestations of specific candidiasis.

scholarly journals Secretory immune status of oral cavity in the patients with Сandida-associated denture stomatitis

2021 ◽  
Vol 23 (3) ◽  
pp. 577-584
Author(s):  
M. E. Malyshev ◽  
A. K. Iordanishvili ◽  
P. A. Mushegyan ◽  
T. G. Khabirova
Keyword(s):  
Candida Albicans ◽  
Oral Cavity ◽  
Antimicrobial Peptides ◽  
Oral Mucosa ◽  
Immunoglobulin A ◽  
Interleukin 4 ◽  
Secretory Immunoglobulin A ◽  
Denture Stomatitis ◽  
Age Related ◽  
Secretory Immunoglobulin

Age-related changes in the oral mucosa immunity, including decreased contents of secretory immunoglobulins and antimicrobial peptides in saliva, along with changed balance of pro- and antiinflammatory cytokines, care risks for development of purulent-inflammatory or allergic diseases of the oral cavity. For example, denture stomatitis (DS) caused by Candida albicans occurs in about 30—70% of denture users. The purpose of this study was to assess the secretory immune state of oral mucous membranes in the patients with Candida-associated denture stomatitis. We examined 42 elderly patients (61-72 years old) with one-piece acrylic dentures for at least, 6 months (15 men and 27 women). Based on clinical and microbiological studies, the patients were divided into a group with DS (n = 24) and a group without DS (n = 18). The contents of secretory immunoglobulin A (sIgA) and proinflammatory cytokines was determined, i.e., interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNFα), and anti-inflammatory cytokines, e.g., receptor antagonist of interleukin-1 (RAIL), interleukin-4 (IL-4), interleukin-10 (IL-10), as well as antimicrobial peptides (cathelicidin LL-37, lactoferrin and alphadefensins 1-3 (HNP1-3). The sIgA levels in the salivary fluid of patients with DS (0.92 (0.80-1.26) g/l) were significantly lower (p < 0.05) than in patients without stomatitis (1.71 (1.23-2,13) g/l). In the group with advanced DS, a significant increase of IL-1β levels in saliva was observed, along with simultaneous decrease of IL-8 concentrations, compared to the other group, without differences in TNFα and IL-6 concentrations. Increased contents of IL-10 in saliva was also noted. It was shown that the concentrations of cathelicidin LL-37 in saliva of the DS patients was increased two-fold, whereas the contents of neutrophil-derived alpha-defensins (HNP 1-3) was decreased. Conclusions: The development of inflammation in denture stomatitis caused by usage of removable acrylic dentures associated with Candida albicans infection is characterized by functional insufficiency of the secretory immunity of the oral mucosa associated with decreased amounts of secretory immunoglobulin A and antimicrobial peptides of neutrophilic origin. Low levels of alpha-defensins may suggest a decrease in the functional activity of neutrophils in the elderly, thus leading to higher susceptibility to fungal infection of oral cavity.

scholarly journals Virulence factors of Candida species from the oral mucosa and prostheses of elderly people from a riverside community in the Amazon state, Brazil

2019 ◽  
Vol 48 ◽  
Author(s):  
Daniela Marinho da SILVA ◽  
Thayana Cruz de SOUZA ◽  
Carol Falcão de Carvalho ALENCAR ◽  
Ingrid da Silva de SOUZA ◽  
Maria Fulgência Costa Lima BANDEIRA ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Elderly People ◽  
Oral Mucosa ◽  
Virulence Factors ◽  
The Elderly ◽  
Oral Microbiota ◽  
Exact Test ◽  
Significant Difference ◽  
Chi Squared ◽  
Amazonas State

Abstract Introduction Candida albicans is the yeast most commonly affecting the oral cavity, sometimes causing infection. However, several factors may be associated with the onset of candidiasis, which may be related not only to the hygiene and health of individuals, but also to the pathogenicity of these microorganisms. Objective To evaluate the virulence factors of Candida yeasts isolated from the oral mucosa of elderly people living in the “Comunidade Lago do Limão”, municipality of Iranduba, Amazonas state, Brazil. Material and method Testes were performed to assess the production of urease, proteinase, phospholipase and hemolysin. Statistical analysis used the Fisher's exact test and the Chi-squared test. Result Prevalence of non-albicans species was observed. As for virulence factors, all isolates were negative ureases, and there was prevalence of very strong proteinase production, whereas most isolates did not produce this enzyme in the phospholipase test. All yeasts analyzed presented hemolysin production, with grade IV hemolysis as the most prevalent. There was no statistically significant difference between the virulence of isolates from the oral cavity and the prostheses of the elderly analyzed. Conclusion Several virulence factors may present with high intensity in the presence of oral microbiota changes. In addition, non-albicans species present number of virulence factors similar to that of C. albicans, with high pathogenicity. This study allows a better analysis of candidiasis prevention strategies aiming to promote improvement in the health and quality of life for the elderly.

scholarly journals Epidemiology of oral mucosal lesions in Slovenia

2018 ◽  
Vol 52 (3) ◽  
pp. 263-266 ◽  
Author(s):  
Andrej Aleksander Kansky ◽  
Vojko Didanovic ◽  
Tadej Dovsak ◽  
Bozana Loncar Brzak ◽  
Ivica Pelivan ◽  
...  
Keyword(s):  
Oral Health ◽  
Oral Cavity ◽  
Oral Mucosa ◽  
Malignant Tumors ◽  
Epidemiological Data ◽  
Denture Stomatitis ◽  
Linea Alba ◽  
Screening Programs ◽  
Oral Mucosal Lesions ◽  
Mucosal Lesions

Abstract Background Among the diseases of oral mucosa, malignant tumors are the most dangerous, but not the most common lesions that might appear in the oral cavity. Since most of the studies are focused on the detection of cancer in the oral cavity, we were interested in detecting the frequency of benign changes of the oral mucosa in Slovene population. Oral mucosal lesions are important pointer of oral health and quality of life, especially in elderly. The prevalence of oral mucosal lesions, together with information on the risk habits associated with oral health, such as tobacco and alcohol use, can help in planning future oral health studies and screening programs. Patients and methods Survey upon oral mucosal lesions was conducted during the national project for oral cancer screening in spring 2017 in the Slovenia in which more than 50% of dentists participated and 2395 patients (904 men and 1491 women) were included. Results Clinical examination, which was conducted according to the WHO standards revealed that 645 patients (27%) had oral mucosal lesions. The ten most common oral lesions detected were fibroma, gingivitis, Fordyce spots, white coated tongue, cheek biting, linea alba, denture stomatitis, geographic tongue, recurrent aphthous ulcerations and lichen planus. Conclusions Overall, these epidemiological data suggest need for specific health policies for prevention, diagnosis and treatment of oral mucosal lesions.

scholarly journals Yeast-Host Interactions: Anadenanthera colubrina Modulates Virulence Factors of C. albicans and Inflammatory Response In Vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Carolina Medeiros de Almeida Maia ◽  
Silvana Pasetto ◽  
Cassiano Francisco Weege Nonaka ◽  
Edja Maria Melo de Brito Costa ◽  
Ramiro Mendonça Murata
Keyword(s):  
Immune Response ◽  
Antifungal Activity ◽  
Virulence Factors ◽  
Fungal Infections ◽  
Oral Candidiasis ◽  
Host Immune Response ◽  
Host Cells ◽  
Broth Microdilution Method ◽  
Cytokines Secretion

Oral candidiasis is one of the most common fungal infections in humans. Its incidence has increased widely, as well as the antifungal resistance, demanding for the search for novel antifungal therapeutic agents. Anadenanthera colubrina (Vell.) Brenan is a plant species that has been proven to possess pharmacological effects, including antifungal and anti-inflammatory activities. This study evaluated in vitro the effects of standardized A. colubrina extract on virulence factors of Candida albicans and its regulation on immune response through C. albicans-host interaction. Antifungal activity was evaluated by Broth Microdilution Method against reference Candida strains (C. albicans, C. glabrata, C. tropicalis; C. dubliniensis). Anti-biofilm effect was performed on C. albicans mature biofilm and quantified by CFU/mL/g of biofilm dry weight. Proleotlytic enzymatic activities of proteinase and phospholipase were assessed by Azocasein and Phosphatidylcholine assays, respectively. Cytotoxicity effect was determined by Cell Titer Blue Viability Assay on Human Gingival Fibroblasts. Co-cultured model was used to analyze C. albicans coexisting with HGF by Scanning Electron Microscopy and fluorescence microscopies; gene expression was assessed by RT-PCR of C. albicans enzymes (SAP-1, PLB-1) and of host inflammatory cytokines (IL-6, IL-8, IL-1β, IL-10). Cytokines secretion was analysed by Luminex. The extract presented antifungal effect with MIC&lt;15.62 μg/ml against Candida strains. Biofilm and proteolytic activity were significant reduced at 312.4 μg/ml (20 × 15.62 μg/ml) extract concentration. Cell viability was maintained higher than 70% in concentrations up to 250 μg/ml (LD50 = 423.3 μg/ml). Co-culture microscopies demonstrated a substantial decreased in C. albicans growth and minimal toxicity against host cells. Gene expressions of SAP-1/PLB-1 were significantly down-regulated and host immune response was modulated by a significant decreased on IL-6 and IL-8 cytokines secretion. A. colubrina had antifungal activity on Candida strains, antibiofilm, and anti-proteolytic enzyme effects against C. albicans. Presented low cytotoxicity to the host cells and modulatory effects on the host immune response.

scholarly journals Perawatan Kandidiasis Pseuodomembran Akut dan Mukositis Oral pada Penderita Kanker Nasofaring yang Menerima Khemoterapi dan Radioterapi

2016 ◽  
Vol 19 (1) ◽  
pp. 182
Author(s):  
S. Supriatno ◽  
Goeno Subagyo
Keyword(s):  
Oral Cavity ◽  
Cancer Patient ◽  
Oral Mucosa ◽  
Clinical Examination ◽  
Oral Mucositis ◽  
Background Radiation ◽  
Oral Candidiasis ◽  
Tissue Destruction ◽  
Results Of Treatment ◽  
White Spots

Latar belakang: Terapi radiasi merupakan metode primer perawatan pasien kanker leher dan kepala. Perubahan funsional dan kerusakan jaringan oral menyebabkan timbulnya mukositia oral yang diikuti dengan kandidiasis oral. Tujuan: Melaporkan efek samping perawatan khemoterapi dan radioterapi pada pasien kanker nasofaring yang terjadi di rongga mulut berupa kandidiasis pseudomembran akut dan mukositis oral serta penatalaksanaannya. Kasus: Seorang laki-laki, 69 tahun, datang ke Bagian Gigi dan Mulut RSUP Dr. Sardjito, atas rujukan dari instalasi Penyakit Dalam., RSUP Dr. Sardjito, dengan keluhan sakit untuk menelan makanan dan mulutnya banyak bercak-bercak putih. Keluhan dirasakan satu minggu setelah dilakukan khemoterapi ke-3 dan radioterapi ke-9. Pasien didiagnosa kanker nasofaring (NPC) dengan klasifikasi T2N3M0. Pemeriksaan klinik menunjukkan adanya lapisan putih pada mukosa lidah, pipi, palatum, dan mukosa bibir. Seluruh mukosa mulut berwarna merah tua dan terdapat anguler cheilitis di kedua sudut bibir. Pasien diklasifikasikan menderita mukositis oral derajat 1. Penatalaksanaan: Menghilangkan jaringan nekrotik dan debris dengan berkumur larutan perhidrol 3% dan pemberian medikasi termasuk tablet nistatin 500.000 IU, betadin kumur, dan larutan perhidrol 3% selama 1 minggu. Saat reevaluasi, pasien sudah dapat menelan dan makan yang sedikit keras tanpa ada rasa sakit lagi. Pemeriksaan klinis didapatkan bercak putih di lidah, palatum, pipi dan bibir sudah tidak ada. Warna mukosa oral telah normal, OHI dan kondisi umum baik dalam 1 minggu pasca perawatan. Kesimpulan: Perawatan kandidiasis dan mukositis oral akibat kemoradioterapi pada pasien kanker nasofaring telah berhasil dan kondisi oral membaik. Pasien dapat mengunyah dan menelan makanan tanpa ada rasa sakit, dan hasil pengobatan yang diberikan pada pasien sesuai dengan harapan operator. Background: Radiation therapy remains the primary method of treatment for patients with head and neck cancer. The tissue destruction and functional alterations in the oral cavity lead to the development of oral mucositis followed by oral candidiasis. Purpose: The aim of study was to report the side effect of chemotherapy and radiotherapy treatment of nasopharyng cancer patient included acute pseudomembran candidiasis and oral mucositis, and its treatment. Case: 69 year old man, came to dental clinic, Sardjito hospital, as refered from Internal Medicine department, Sardjito hospital, with complained painful for food swallowing and found white spots at oral cavity. Chief complaint was detected one week after third chemotherapy and nine radiotherapy treatments. Nasopharyng cancer was diagnosed with T2N3M0 clasifiacation. Clinical examination showed white spots at tongue, buccal, palatal and lip mucosa. All of oral mucosa coloured bright-red and anguler cheilitis appeared at both lip angle. Patient was clasified (by WHO) to have oral mucositis with level 1. Management: removal of necrotic tissue and debris using perhidrol 3% solution, and also medication by nistatin tablet 500.000 IU, betadin gargle, and perhidrol 3% solution for 1 week. In control, patient feeled comfortable while food swallowing and could eat a slightly hard food without pain. Clinical examination revealed that white spot at tongue, buccal, palatal and lip mucosa was disappeared. Normal colour was found at all of oral mucosa. Also, oral hygiene and general condition were good in 1 week post treatment. Conclusion: Treatment of acute pseudomembran candidiasis and oral mucositis caused by chemotherapy and radiotherapy of nasopharyng cancer patient was recovered. Patient could chew and swallow of food without painful, and results of treatment to this pastient gave us a satisfied.

scholarly journals PREVENTION OF CANDIDIASIS IN PATIENTS USING REMOVABLE DENTURES

2021 ◽  
Vol 29 (31) ◽  
pp. 43-53
Author(s):  
Andrey SEVBITOV ◽  
Aleksey DOROFEEV ◽  
Sergey MIRONOV ◽  
Samer AL-KHOURY ◽  
Anton TIMOSHIN
Keyword(s):  
Oral Cavity ◽  
Oral Mucosa ◽  
Oral Candidiasis ◽  
Age Groups ◽  
Local Immunity ◽  
Thermal Insulating ◽  
The World ◽  
Removable Plate ◽  
Orthopedic Care ◽  
Opportunistic Mycoses

Background: Despite innovations in orthopedic dentistry, the manufacture of removable dentures belongs to the most popular orthopedic care category. Removable dentures are combined stimuli that affect the mucous membrane and neuro-receptor apparatus. Acrylic plastic prostheses, widely used in prosthetic dentistry, have a negative side mechanical, chemical-toxic, sensitizing, and thermal insulating effect on oral tissue and prosthetic impression area. This is often complicated by a violation of the biocenosis of the oral cavity, the growth of pathogenic microflora that releases toxins, especially an increase in the number of yeast colonies that irritate the oral mucosa and prosthetic stomatitis. According to the WHO, one-fifth of the world s population suffers or has suffered various candidiasis forms at least once. The worldwide increase in the incidence of the disease is primarily related to the fact that this infection is opportunistic, more than half of the world s population is a carrier of fungi of this kind, i.e., in most cases, it is an endogenous infection, which makes candidiasis different from other opportunistic mycoses. Aims: The purpose of this study was to study the prevalence of candidiasis in patients using removable dentures and to evaluate the effectiveness and prevention of candidiasis treatment. Methods: 100 patients with oral candidiasis of various age groups from 45 to 65 years were observed. Of these, 60 patients with removable plate prostheses; 40 patients with partially removable prostheses. Results and Discussion: Chronic forms of candidiasis were diagnosed in 40 patients and with exacerbation of chronic forms of candidiasis-60 people. The number of untreated carious cavities and poor hygienic condition of the oral cavity directly affects the severity of candidiasis. Acute forms of candidiasis were observed mainly in patients with high DMF and PMA indices. The severity of candidiasis depends on the degree and duration of wearing dentures and hygienic conditions - the most severe forms of invasive candidiasis were observed in the presence of removable plate prostheses, the complete absence of teeth, and the use of a prosthesis for more than 10-15 years. A combined lesion of the oral mucosa and the red border of the lips was observed mainly in patients older than 60 years. Conclusions: The presence of candidiasis in the oral cavity in patients with removable plate prostheses leads to a statistically significant change in the indicators of local immunity of the oral cavity: an increase in the concentration of serum IgG and IgA and the values of the coefficient of the balance of local immunity factors.

scholarly journals Use of Proteins Identified through a Functional Genomic Screen To Develop a Protein Subunit Vaccine That Provides Significant Protection against Virulent Streptococcus suis in Pigs

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Susan L. Brockmeier ◽  
Crystal L. Loving ◽  
Tracy L. Nicholson ◽  
Jinhong Wang ◽  
Sarah E. Peters ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Trial ◽  
Streptococcus Suis ◽  
Protein Subunit ◽  
Content Type ◽  
Degree Of Protection ◽  
Wide Range ◽  
Associated Proteins ◽  
Clinical Protection ◽  
Cellular Immune

ABSTRACT Streptococcus suis is a bacterium that is commonly carried in the respiratory tract and that is also one of the most important invasive pathogens of swine, commonly causing meningitis, arthritis, and septicemia. Due to the existence of many serotypes and a wide range of immune evasion capabilities, efficacious vaccines are not readily available. The selection of S. suis protein candidates for inclusion in a vaccine was accomplished by identifying fitness genes through a functional genomics screen and selecting conserved predicted surface-associated proteins. Five candidate proteins were selected for evaluation in a vaccine trial and administered both intranasally and intramuscularly with one of two different adjuvant formulations. Clinical protection was evaluated by subsequent intranasal challenge with virulent S. suis . While subunit vaccination with the S. suis proteins induced IgG antibodies to each individual protein and a cellular immune response to the pool of proteins and provided substantial protection from challenge with virulent S. suis , the immune response elicited and the degree of protection were dependent on the parenteral adjuvant given. Subunit vaccination induced IgG reactive against different S. suis serotypes, indicating a potential for cross protection.

scholarly journals Individual Expression of Hepatitis A Virus 3C Protease Induces Ferroptosis in Human Cells In Vitro

2021 ◽  
Vol 22 (15) ◽  
pp. 7906
Author(s):  
Alexey A. Komissarov ◽  
Maria A. Karaseva ◽  
Marina P. Roschina ◽  
Andrey V. Shubin ◽  
Nataliya A. Lunina ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Proteolytic Enzymes ◽  
Morphological Changes ◽  
Human Cells ◽  
Mitochondrial Potential ◽  
3C Protease ◽  
Wide Range

Regulated cell death (RCD) is a fundamental process common to nearly all living beings and essential for the development and tissue homeostasis in animals and humans. A wide range of molecules can induce RCD, including a number of viral proteolytic enzymes. To date, numerous data indicate that picornaviral 3C proteases can induce RCD. In most reported cases, these proteases induce classical caspase-dependent apoptosis. In contrast, the human hepatitis A virus 3C protease (3Cpro) has recently been shown to cause caspase-independent cell death accompanied by previously undescribed features. Here, we expressed 3Cpro in HEK293, HeLa, and A549 human cell lines to characterize 3Cpro-induced cell death morphologically and biochemically using flow cytometry and fluorescence microscopy. We found that dead cells demonstrated necrosis-like morphological changes including permeabilization of the plasma membrane, loss of mitochondrial potential, as well as mitochondria and nuclei swelling. Additionally, we showed that 3Cpro-induced cell death was efficiently blocked by ferroptosis inhibitors and was accompanied by intense lipid peroxidation. Taken together, these results indicate that 3Cpro induces ferroptosis upon its individual expression in human cells. This is the first demonstration that a proteolytic enzyme can induce ferroptosis, the recently discovered and actively studied type of RCD.

Sign in / Sign up

Export Citation Format

Share Document