Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006849 (oral candidiasis)
1,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histatins are a family of histidine-rich, cationic peptides composed of up to 38 amino acids. They are secreted by the salivary glands of humans and some subhuman primates and are thought to be part of the host defence system in the oral cavity. Histatins exhibit in vitro activity against both bacteria and yeast, common to other antimicrobial peptides. Because of these activities, histatin-based peptides could play an important role in the treatment and prevention of infectious diseases. A 12 amino acid amidated fragment of histatin 5, designated P-113, has been identified as the smallest fragment that retains antimicrobial activity comparable to the parent compound. Animal studies and human clinical trials showed that P-113 has potential in preventing the development of gingivitis, with no adverse side effects. Histatin peptides also could be used for other therapeutic applications in which the infection is localised and accessible via topical delivery, such as treatment of candidiasis (thrush) and mucositis in the oral cavity, skin infections and treatment of lung infections afflicting cystic fibrosis patients.
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PMID:Histatin-derived peptides: potential agents to treat localised infections. 1598 35

Persisters are dormant variants of regular cells that form stochastically in microbial populations and are highly tolerant to antibiotics. High persister (hip) mutants of Pseudomonas aeruginosa are selected in patients with cystic fibrosis. Similarly, hip mutants of Candida albicans are selected in patients with an oral thrush biofilm. These observations suggest that persisters may be the main culprit responsible for the recalcitrance of chronic infectious disease to antimicrobial therapy. Screening knockout libraries has not produced mutants lacking persisters, indicating that dormancy mechanisms are redundant. Toxin/antitoxin (TA) modules are involved in persister formation in Escherichia coli. The SOS response leads to overexpression of the TisB toxin and persister formation. TisB is a membrane-acting peptide that apparently sends cells into dormancy by decreasing the proton motive force and ATP levels. Stress responses may act as general activators of persister formation. Proteins required for maintaining persisters may represent realistic targets for discovery of drugs capable of effectively treating chronic infections.
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PMID:Persister cells. 2052 88

Biofilms have been found to be involved in a wide variety of microbial infections in the body, by one estimate 80% of all infections. Infectious processes in which biofilms have been implicated include common problems such as urinary tract infections, catheter infections, middle-ear infections, sinusitis, formation of dental plaque, gingivitis, coating contact lenses, endocarditis, infections in cystic fibrosis, and infections of permanent indwelling devices such as joint prostheses and heart valves. Bacteria living in a biofilm usually have significantly different properties from free-floating bacteria of the same species, as the dense and protected environment of the film allows them to cooperate and interact in various ways. One benefit of this environment is increased resistance to detergents and antibiotics, as the dense extracellular matrix and the outer layer of cells protect the interior of the community. In some cases antibiotic resistance can be increased 1000-fold. Also, the biofilm bacteria excrete toxins that reversibly block important processes such as translation and protecting the cell from bactericidal antibiotics that are ineffective against inactive targets. In the head and neck area, biofilms are a major etiologic factor in periodontitis, wound infections, oral candidiasis, and sinus and ear infections. For the past several decades, photodynamic treatment has been reported in the literature to be effective in eradicating various microorganisms using different photosensitizers, different wavelengths of light, and different light sources. PDT has been further studied to demonstrate its effectiveness for the eradication of both Gram-negative and Gram-positive antibiotic-resistant bacteria. This chapter will focus on the use of PDT in the treatment of antibiotic-resistant biofilms, antibiotic-resistant wound infections, and azole-resistant oral candidiasis using methylene blue-based photodynamic therapy.
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PMID:Photodynamic therapy of bacterial and fungal biofilm infections. 2055 48

It is a given that new antibiotics are needed to combat drug-resistant pathogens. However, this is only a part of the need-we actually never had antibiotics capable of eradicating an infection. All pathogens produce a small subpopulation of dormant persister cells that are highly tolerant to killing by antibiotics. Once an antibiotic concentration drops, surviving persisters re-establish the population, causing a relapsing chronic infection. Persisters are especially significant when the pathogen is shielded from the immune system by biofilms, or in sites where the immune components are limited-in the nervous system, the stomach, or inside macrophages.Antibiotic treatment during a prolonged chronic infection of P. aeruginosa in the lungs of patients with cystic fibrosis selects for high-persister (hip) mutants. Similarly, treatment of oral thrush infection selects for hip mutants of C. albicans. These observations suggest a direct causality between persisters and recalcitrance of the disease. It appears that tolerance of persisters plays a leading role in chronic infections, while resistance is the leading cause of recalcitrance to therapy in acute infections. Studies of persister formation in E. coli show that mechanisms of dormancy are highly redundant. Isolation of persisters produced a transcriptome which suggests a dormant phenotype characterized by downregulation of energy-producing and biosynthetic functions. Toxin-antitoxin modules represent a major mechanism of persister formation. The RelE toxin causes dormancy by cleaving mRNA; the HipA toxin inhibits translation by phosphorylating elongation factor Ef-Tu, and the TisB toxin forms a membrane pore, leading to a decrease in pmf and ATP.
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PMID:Persister cells: molecular mechanisms related to antibiotic tolerance. 2309 May 99

Mucus forms a protective coating on wet epithelial surfaces throughout the body that houses the microbiota and plays a key role in host defense. Mucins, the primary structural components of mucus that creates its viscoelastic properties, are critical components of the gel layer that protect against invading pathogens. Altered mucin production has been implicated in diseases such as ulcerative colitis, asthma, and cystic fibrosis, which highlights the importance of mucins in maintaining homeostasis. Different types of mucins exist throughout the body in various locations such as the gastrointestinal tract, lungs, and female genital tract, but this review will focus on mucins in the oral cavity. Salivary mucin structure, localization within the oral cavity, and defense mechanisms will be discussed. These concepts will then be applied to present what is known about the protective function of mucins in oral diseases such as HIV/AIDS, oral candidiasis, and dental caries.
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PMID:Salivary mucins in host defense and disease prevention. 2670 Dec 74

We aimed to estimate for the first time the burden of fungal infections in Uruguay. Data on population characteristics and underlying conditions were extracted from the National Statistics Institute, the World Bank, national registries, and published articles. When no data existed, risk populations were used to estimate frequencies extrapolating from the literature. Population structure (inhabitants): total 3,444,006; 73% adults; 35% women younger than 50 years. Size of populations at risk (total cases per year): HIV infected 12,000; acute myeloid leukemia 126; hematopoietic stem cell transplantation 30; solid organ transplants 134; COPD 272,006; asthma in adults 223,431; cystic fibrosis in adults 48; tuberculosis 613; lung cancer 1400. Annual incidence estimations per 100,000: invasive aspergillosis, 22.4; candidemia, 16.4; Candida peritonitis, 3.7; Pneumocystis jirovecii pneumonia, 1.62; cryptococcosis, 0.75; severe asthma with fungal sensitization, 217; allergic bronchopulmonary aspergillosis, 165; recurrent Candida vaginitis, 6323; oral candidiasis, 74.5; and esophageal candidiasis, 25.7. Although some under and overestimations could have been made, we expect that at least 127,525 people suffer from serious fungal infections each year. Sporothrichosis, histoplasmosis, paracoccidioidomycosis, and dermatophytosis are known to be frequent but no data are available to make accurate estimations. Given the magnitude of the burden of fungal infections in Uruguay, efforts should be made to improve surveillance, strengthen laboratory diagnosis, and warrant access to first line antifungals.
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PMID:Estimating the Burden of Serious Fungal Infections in Uruguay. 2956 41

For the first time, we aimed to estimate the burden of serious fungal infections or diseases (SFD) and highlight national epidemiological features in Serbia. Data on population and underlining conditions were extracted from the Statistical Office of the Republic of Serbia, World Bank, the Institute of Public Health of Serbia, the World Health Organization, National reference laboratory for medical mycology, the national registries of Serbian professional societies, and relevant publications. The population structure/inhabitants in 2016 (not including the autonomous region Kosovo & Metohija) was 7,058,322; with 6,041,743 adults (85.6%). The populations at risk (total cases per year) were: HIV infected 2441; acute myeloid leukemia 212; stem cell transplantation 151; solid organ transplants 59; chronic obstructive pulmonary disease 250,302; adult asthmatics 311,806; adult cystic fibrosis 65; pulmonary tuberculosis 898; lung cancer 7260; intensive care unit admissions 19,821; and renal support 520. Annual fungal disease cases estimated are: candidemia 518; invasive aspergillosis 619; Candida peritonitis 187; Pneumocystis jirovecii pneumonia 62; cryptococcosis 5; mucormycosis or fusariosis 23; severe asthma with fungal sensitization 10,393; allergic bronchopulmonary aspergillosis 9094; chronic pulmonary aspergillosis 448, recurrent Candida vaginitis 135,303; oral candidiasis 208,489; esophageal candidiasis 173, fungal keratitis 70; tinea capitis 300; and onychomycosis 342,721. We expect that 156,825 people suffer from serious SFD each year (2221/100,000), and 409 dies annually. Additionally, the prevalence of superficial infections exceeds 1,008,995 cases (14,295/100,000). The first Rhinosporidium outbreak in Europe was associated with Serbian Silver Lake. The plant pathogen Fusarium seems to be emerging in Serbian pediatric haematooncology settings. Candida auris and endemic mycoses have not been observed to date. These general estimates provide a primer for further efforts to study fungal epidemiology in Serbia.
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PMID:Estimated Burden of Serious Fungal Diseases in Serbia. 2994 24