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1.
Vopr Virusol ; 68(2): 152-160, 2023 05 18.
Article in Russian | MEDLINE | ID: covidwho-20242884

ABSTRACT

INTRODUCTION: The COVID-19 pandemic combined with seasonal epidemics of respiratory viral diseases requires targeted antiviral prophylaxis with restorative and immunostimulant drugs. The compounds of natural origin are low-toxic, but active against several viruses at the same time. One of the most famous compounds is Inonotus obliquus aqueous extract. The fruit body of basidial fungus I. obliquus is called Chaga mushroom. The aim of the work ‒ was to study the antiviral activity of I. obliquus aqueous extract against the SARS-CoV-2 virus in vivo. MATERIALS AND METHODS: Antiviral activity of I. obliquus aqueous extract sample (#20-17) was analyzed against strain of SARS-CoV-2 Omicron ВА.5.2 virus. The experiments were carried out in BALB/c inbred mice. The SARS-CoV-2 viral load was measured using quantitative real-time PCR combined with reverse transcription. The severity of lung tissue damage was assessed by histological methods. RESULTS: The peak values of the viral load in murine lung tissues were determined 72 hours after intranasal inoculation at dose of 2,85 lg TCID50. The quantitative real-time PCR testing has shown a significant decrease in the viral load compared to the control group by 4,65 lg copies/ml and 5,72 lg copies/ml in the lung tissue and nasal cavity samples, respectively. Histological methods revealed that the decrease in the number and frequency of observed pathomorphological changes in murine lung tissues depended on the introduction of the compound under study. CONCLUSION: The results obtained indicate the possibility of using basidial fungus Inonotus obliquus aqueous extract as a preventive agent against circulating variants of SARS-CoV-2 virus.


Subject(s)
Basidiomycota , COVID-19 , Coronaviridae , Severe acute respiratory syndrome-related coronavirus , Humans , Mice , Animals , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Mice, Inbred BALB C , Pandemics , Fungi
2.
Int J Mol Sci ; 24(10)2023 May 18.
Article in English | MEDLINE | ID: covidwho-20235991

ABSTRACT

A new series of 4-((7-methoxyquinolin-4-yl) amino)-N-(substituted) benzenesulfonamide 3(a-s) was synthesized via the reaction of 4-chloro-7-methoxyquinoline 1 with various sulfa drugs. The structural elucidation was verified based on spectroscopic data analysis. All the target compounds were screened for their antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and unicellular fungi. The results revealed that compound 3l has the highest effect on most tested bacterial and unicellular fungal strains. The highest effect of compound 3l was observed against E. coli and C. albicans with MIC = 7.812 and 31.125 µg/mL, respectively. Compounds 3c and 3d showed broad-spectrum antimicrobial activity, but the activity was lower than that of 3l. The antibiofilm activity of compound 3l was measured against different pathogenic microbes isolated from the urinary tract. Compound 3l could achieve biofilm extension at its adhesion strength. After adding 10.0 µg/mL of compound 3l, the highest percentage was 94.60% for E. coli, 91.74% for P. aeruginosa, and 98.03% for C. neoformans. Moreover, in the protein leakage assay, the quantity of cellular protein discharged from E. coli was 180.25 µg/mL after treatment with 1.0 mg/mL of compound 3l, which explains the creation of holes in the cell membrane of E. coli and proves compound 3l's antibacterial and antibiofilm properties. Additionally, in silico ADME prediction analyses of compounds 3c, 3d, and 3l revealed promising results, indicating the presence of drug-like properties.


Subject(s)
Anti-Infective Agents , Urinary Tract Infections , Escherichia coli , Structure-Activity Relationship , Microbial Sensitivity Tests , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Sulfanilamide/pharmacology , Sulfonamides/pharmacology , Fungi , Biofilms
3.
Korean J Gastroenterol ; 81(5): 221-225, 2023 05 25.
Article in English | MEDLINE | ID: covidwho-20232586

ABSTRACT

Gastrointestinal mucormycosis is a rare disease with a significant mortality rate, even when promptly diagnosed and treated. An unusual complication was observed in India during the second wave of coronavirus disease 2019 (COVID-19). Two incidences of gastric mucormycosis were found. A 53-year-old male patient with a history of COVID-19 one month earlier came into the intensive care unit. After admission, the patient developed hematemesis, which was initially treated with blood transfusions and digital subtraction angiography embolization. Esophagogastroduodenoscopy (EGD) revealed a large ulcer with a clot in the stomach. During an exploratory laparotomy, the proximal stomach was necrotic. Histopathological examination confirmed mucormycosis. The patient was started on antifungals, but despite rigorous therapy, the patient died on the tenth postoperative day. Another patient, an 82-year-old male with a history of COVID-19, arrived with hematemesis two weeks earlier and was treated conservatively. EGD revealed a large white-based ulcer with abundant slough along the larger curvature of the body. Mucormycosis was verified by biopsy. He was treated with amphotericin B and isavuconazole. He was discharged after two weeks in a stable condition. Despite quick detection and aggressive treatment, the prognosis is poor. In the second case, prompt diagnosis and treatment saved the patient's life.


Subject(s)
COVID-19 , Mucormycosis , Male , Humans , Middle Aged , Aged, 80 and over , Hematemesis/etiology , Mucormycosis/complications , Mucormycosis/diagnosis , Ulcer , COVID-19/complications , Fungi
4.
Front Cell Infect Microbiol ; 13: 1162721, 2023.
Article in English | MEDLINE | ID: covidwho-2312110

ABSTRACT

Background: Antimicrobial resistance is a serious threat to public health globally. It is a slower-moving pandemic than COVID-19, so we are fast running out of treatment options. Purpose: Thus, this study was designed to search for an alternative biomaterial with broad-spectrum activity for the treatment of multidrug-resistant (MDR) bacterial and fungal pathogen-related infections. Methods: We isolated Streptomyces species from soil samples and identified the most active strains with antimicrobial activity. The culture filtrates of active species were purified, and the bioactive metabolite extracts were identified by thin-layer chromatography (TLC), preparative high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentrations (MICs) of the bioactive metabolites against MDR bacteria and fungi were determined using the broth microdilution method. Results: Preliminary screening revealed that Streptomyces misakiensis and S. coeruleorubidus exhibited antimicrobial potential. The MIC50 and MIC90 of S. misakiensis antibacterial bioactive metabolite (ursolic acid methyl ester) and antifungal metabolite (tetradecamethylcycloheptasiloxane) against all tested bacteria and fungi were 0.5 µg/ml and 1 µg/mL, respectively, versus S. coeruleorubidus metabolites: thiocarbamic acid, N,N-dimethyl, S-1,3-diphenyl-2-butenyl ester against bacteria (MIC50: 2 µg/ml and MIC90: 4 µg/mL) and fungi (MIC50: 4 µg/ml and MIC90: 8 µg/mL). Ursolic acid methyl ester was active against ciprofloxacin-resistant strains of Streptococcus pyogenes, S. agalactiae, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovars, colistin-resistant Aeromonas hydrophila and K. pneumoniae, and vancomycin-resistant Staphylococcus aureus. Tetradecamethylcycloheptasiloxane was active against azole- and amphotericin B-resistant Candida albicans, Cryptococcus neoformans, C. gattii, Aspergillus flavus, A. niger, and A. fumigatus. Ursolic acid methyl ester was applied in vivo for treating S. aureus septicemia and K. pneumoniae pneumonia models in mice. In the septicemia model, the ursolic acid methyl ester-treated group had a significant 4.00 and 3.98 log CFU/g decrease (P < 0.05) in liver and spleen tissue compared to the infected, untreated control group. Lung tissue in the pneumonia model showed a 2.20 log CFU/g significant decrease in the ursolic acid methyl ester-treated group in comparison to the control group. The haematological and biochemical markers in the ursolic acid methyl ester-treated group did not change in a statistically significant way. Moreover, no abnormalities were found in the histopathology of the liver, kidneys, lungs, and spleen of ursolic acid methyl ester-treated mice in comparison with the control group. Conclusion: S. misakiensis metabolite extracts are broad-spectrum antimicrobial biomaterials that can be further investigated for the potential against MDR pathogen infections. Hence, it opens up new horizons for exploring alternative drugs for current and reemerging diseases.


Subject(s)
Anti-Infective Agents , COVID-19 , Methicillin-Resistant Staphylococcus aureus , Pneumonia , Sepsis , Mice , Animals , Staphylococcus aureus , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/pharmacology , Bacteria , Fungi , Microbial Sensitivity Tests , Pneumonia/drug therapy , Klebsiella pneumoniae , Sepsis/drug therapy
5.
Int J Antimicrob Agents ; 62(1): 106846, 2023 07.
Article in English | MEDLINE | ID: covidwho-2315903

ABSTRACT

The COVID-19 pandemic has highlighted the detrimental effect of secondary pathogens in patients with a primary viral insult. In addition to superinfections with bacterial pathogens, invasive fungal infections were increasingly reported. The diagnosis of pulmonary fungal infections has always been challenging; however, it became even more problematic in the setting of COVID-19, particularly regarding the interpretation of radiological findings and mycology test results in patients with these infections. Moreover, prolonged hospitalization in ICU, coupled with underlying host factors. such as preexisting immunosuppression, use of immunomodulatory agents, and pulmonary compromise, caused additional vulnerability to fungal infections in this patient population. In addition, the heavy workload, redeployment of untrained staff, and inconsistent supply of gloves, gowns, and masks during the COVID-19 outbreak made it harder for healthcare workers to strictly adhere to preventive measures for infection control. Taken together, these factors favored patient-to-patient spread of fungal infections, such as those caused by Candida auris, or environment-to-patient transmission, including nosocomial aspergillosis. As fungal infections were associated with increased morbidity and mortality, empirical treatment was overly used and abused in COVID-19-infected patients, potentially contributing to increased resistance in fungal pathogens. The aim of this paper was to focus on essential elements of antifungal stewardship in COVID-19 for three fungal infections, COVID-19-associated candidemia (CAC), -pulmonary aspergillosis (CAPA), and -mucormycosis (CAM).


Subject(s)
COVID-19 , Candidemia , Humans , Antifungal Agents/therapeutic use , COVID-19/epidemiology , Pandemics , Candidemia/drug therapy , Fungi
6.
Cent Eur J Public Health ; 31(1): 63-68, 2023 03.
Article in English | MEDLINE | ID: covidwho-2315403

ABSTRACT

OBJECTIVES: Indoor air toxicity is of major public health concern due to the increase in humidity-induced indoor mould exposure and associated health changes. The objective is to present evidence for the causality of health threats and indoor mould exposure. METHODS: PubMed search on the following keywords: dampness, mould, indoor air quality, public health, dampness, and mould hypersensitivity syndrome, sick building syndrome, and building-related illness as well as information from the health authorities of Bavaria and North Rhine-Westphalia, the Center of Disease Control (CDC), World Health Organisation (WHO), and guidelines of professional societies. RESULTS: The guidelines of professional societies published in 2017 are decisive for the assessment of the impact of mould pollution caused by moisture damage on human health and for official regulations in Germany. Until 2017, a causal connection between moisture damage and mould exposure could usually only be established for pulmonary diseases. The health risk of fungal components is apparent as documented in the fungal priority pathogens list (FPPL) of the WHO. Since 2017, studies, especially in Scandinavia, have proved causality between moisture and mould exposure not only for pulmonary diseases but also for extrapulmonary diseases and symptoms. This was made possible by new test methods for determining the toxicity of fungal components in indoor air. Environmental medical syndromes, e.g., dampness and mould hypersensitivity syndrome (DMHS), sick building syndrome (SBS), building-related symptoms (BRS), and building-related illness (BRI), and fungal pathogens, e.g., Aspergillus fumigatus, pose a major threat to public health. CONCLUSION: There is evidence for the causality of moisture-induced indoor moulds and severe health threats in these buildings. According to these findings, it is no longer justifiable to ignore or trivialize the mould contamination induced by moisture damage and its effects on pulmonary and extrapulmonary diseases. The health and economic implications of these attitudes are clear.


Subject(s)
Air Pollution, Indoor , Lung Diseases , Sick Building Syndrome , Surgeons , Humans , Air Pollution, Indoor/adverse effects , Air Pollution, Indoor/analysis , Fungi , Humidity
7.
J Antimicrob Chemother ; 77(Suppl_2): ii21-ii34, 2022 11 25.
Article in English | MEDLINE | ID: covidwho-2315379

ABSTRACT

Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In particular, severe fungal infections are becoming increasingly common in ICUs, affecting people within and outside of traditional risk groups alike. This is exemplified by the emergence of severe viral pneumonia as a significant risk factor for invasive pulmonary aspergillosis, and the recognition of influenza-associated pulmonary aspergillosis and, more recently, COVID-19-associated pulmonary aspergillosis. The treatment landscape for haematological malignancies has changed considerably in recent years, and some recently introduced targeted agents, such as ibrutinib, are increasing the risk of invasive fungal infections. Consideration must also be given to the risk of drug-drug interactions between mould-active azoles and small-molecule kinase inhibitors. At the same time, infections caused by rare moulds and yeasts are increasing, and diagnosis continues to be challenging. There is growing concern about azole resistance among both moulds and yeasts, mandating continuous surveillance and personalized treatment strategies. It is anticipated that the epidemiology of fungal infections will continue to change and that new populations will be at risk. Early diagnosis and appropriate treatment remain the most important predictors of survival, and broad-spectrum antifungal agents will become increasingly important. Liposomal amphotericin B will remain an essential therapeutic agent in the armamentarium needed to manage future challenges, given its broad antifungal spectrum, low level of acquired resistance and limited potential for drug-drug interactions.


Subject(s)
COVID-19 Drug Treatment , Invasive Fungal Infections , Mycoses , Pulmonary Aspergillosis , Humans , Mycoses/drug therapy , Mycoses/epidemiology , Mycoses/diagnosis , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/epidemiology , Azoles/therapeutic use , Fungi , Pulmonary Aspergillosis/drug therapy
8.
Biosens Bioelectron ; 234: 115356, 2023 Aug 15.
Article in English | MEDLINE | ID: covidwho-2310195

ABSTRACT

The COVID-19 pandemic ignited massive research into the rapid detection of bioaerosols. In particular, nanotechnology-based detection strategies are proposed as alternatives because of issues in bioaerosol enrichment and lead time for molecular diagnostics; however, the practical implementation of such techniques is still unclear due to obstacles regarding the large research and development effort and investment for the validation. The use of adenosine triphosphate (ATP) bioluminescence (expressed as relative luminescence unit (RLU) per unit volume of air) of airborne particulate matter (PM) to determine the bacterial population as a representative of the total bioaerosols (viruses, bacteria, and fungi) has been raised frequently because of the high reponse speed, resolution, and compatibility with culture-based bioaerosol monitoring. On the other hand, additional engineering attempts are required to confer significance because of the size-classified (bioluminescence for different PM sizes) and specific (bioluminescence per unit PM mass) biological risks of air for providing proper interventions in the case of airborne transmission. In this study, disc-type impactors to cut-off aerosols larger than 1 µm, 2.5 µm, and 10 µm were designed and constructed to collect PM1, PM2.5, and PM10 on sampling swabs. This engineering enabled reliable size-classified bioluminescence signals using a commercial ATP luminometer after just 5 min of air intake. The simultaneous operations of a six-stage Andersen impactor and optical PM spectrometers were conducted to determine the correlations between the resulting RLU and colony forming unit (CFU; from the Andersen impactor) or PM mass concentration (deriving specific bioluminescence).


Subject(s)
Biosensing Techniques , COVID-19 , Humans , Adenosine Triphosphate/analysis , Pandemics , Air Microbiology , Biosensing Techniques/methods , COVID-19/diagnosis , Respiratory Aerosols and Droplets , Bacteria , Fungi , Environmental Monitoring/methods , Particle Size
9.
Molecules ; 28(8)2023 Apr 18.
Article in English | MEDLINE | ID: covidwho-2304471

ABSTRACT

This study aimed to assess the markers of chemical and microbiological contamination of the air at sport centers (e.g., the fitness center in Poland) including the determination of particulate matter, CO2, formaldehyde (DustTrak™ DRX Aerosol Monitor; Multi-functional Air Quality Detector), volatile organic compound (VOC) concentration (headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry), the number of microorganisms in the air (culture methods), and microbial biodiversity (high-throughput sequencing on the Illumina platform). Additionally the number of microorganisms and the presence of SARS-CoV-2 (PCR) on the surfaces was determined. Total particle concentration varied between 0.0445 mg m-3 and 0.0841 mg m-3 with the dominance (99.65-99.99%) of the PM2.5 fraction. The CO2 concentration ranged from 800 ppm to 2198 ppm, while the formaldehyde concentration was from 0.005 mg/m3 to 0.049 mg m-3. A total of 84 VOCs were identified in the air collected from the gym. Phenol, D-limonene, toluene, and 2-ethyl-1-hexanol dominated in the air at the tested facilities. The average daily number of bacteria was 7.17 × 102 CFU m-3-1.68 × 103 CFU m-3, while the number of fungi was 3.03 × 103 CFU m-3-7.34 × 103 CFU m-3. In total, 422 genera of bacteria and 408 genera of fungi representing 21 and 11 phyla, respectively, were detected in the gym. The most abundant bacteria and fungi (>1%) that belonged to the second and third groups of health hazards were: Escherichia-Shigella, Corynebacterium, Bacillus, Staphylococcus, Cladosporium, Aspergillus, and Penicillium. In addition, other species that may be allergenic (Epicoccum) or infectious (Acinetobacter, Sphingomonas, Sporobolomyces) were present in the air. Moreover, the SARS-CoV-2 virus was detected on surfaces in the gym. The monitoring proposal for the assessment of the air quality at a sport center includes the following markers: total particle concentration with the PM2.5 fraction, CO2 concentration, VOCs (phenol, toluene, and 2-ethyl-1-hexanol), and the number of bacteria and fungi.


Subject(s)
Air Pollution, Indoor , COVID-19 , Mitosporic Fungi , Occupational Exposure , Occupational Exposure/analysis , Carbon Dioxide/analysis , Air Microbiology , COVID-19/epidemiology , SARS-CoV-2 , Respiratory Aerosols and Droplets , Fungi , Bacteria , Particulate Matter/analysis , Phenols/analysis , Air Pollution, Indoor/analysis , Environmental Monitoring
10.
ACS Appl Bio Mater ; 6(5): 1981-1991, 2023 05 15.
Article in English | MEDLINE | ID: covidwho-2296132

ABSTRACT

Numerous disinfection methods have been developed to reduce the transmission of infectious diseases that threaten human health. However, it still remains elusively challenging to develop eco-friendly and cost-effective methods that deactivate a wide range of pathogens, from viruses to bacteria and fungi, without doing any harm to humans or the environment. Herein we report a natural spraying protocol, based on a water-dispersible supramolecular sol of nature-derived tannic acid (TA) and Fe3+, which is easy-to-use and low-cost. Our formulation effectively deactivates viruses (influenza A viruses, SARS-CoV-2, and human rhinovirus) as well as suppressing the growth and spread of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Acinetobacter baumannii) and fungi (Pleurotus ostreatus and Trichophyton rubrum). Its versatile applicability in a real-life setting is also demonstrated against microorganisms present on the surfaces of common household items (e.g., air filter membranes, disposable face masks, kitchen sinks, mobile phones, refrigerators, and toilet seats).


Subject(s)
Anti-Infective Agents , COVID-19 , Viruses , Humans , Polyphenols/pharmacology , SARS-CoV-2 , COVID-19/prevention & control , Anti-Infective Agents/pharmacology , Disinfection/methods , Bacteria , Escherichia coli , Fungi
11.
Semin Immunol ; 66: 101728, 2023 03.
Article in English | MEDLINE | ID: covidwho-2262815

ABSTRACT

The respiratory tree maintains sterilizing immunity against human fungal pathogens. Humans inhale ubiquitous filamentous molds and geographically restricted dimorphic fungal pathogens that form small airborne conidia. In addition, pathogenic yeasts, exemplified by encapsulated Cryptococcus species, and Pneumocystis pose significant fungal threats to the lung. Classically, fungal pneumonia occurs in immune compromised individuals, specifically in patients with HIV/AIDS, in patients with hematologic malignancies, in organ transplant recipients, and in patients treated with corticosteroids and targeted biologics that impair fungal immune surveillance in the lung. The emergence of fungal co-infections during severe influenza and COVID-19 underscores the impairment of fungus-specific host defense pathways in the lung by respiratory viruses and by medical therapies to treat viral infections. Beyond life-threatening invasive syndromes, fungal antigen exposure can exacerbate allergenic disease in the lung. In this review, we discuss emerging principles of lung-specific antifungal immunity, integrate the contributions and cooperation of lung epithelial, innate immune, and adaptive immune cells to mucosal barrier immunity, and highlight the pathogenesis of fungal-associated allergenic disease. Improved understanding of fungus-specific immunity in the respiratory tree has paved the way to develop improved diagnostic, pre-emptive, therapeutic, and vaccine approaches for fungal diseases of the lung.


Subject(s)
COVID-19 , Mycoses , Humans , Lung , Fungi , Immunity, Innate
12.
Trends Immunol ; 44(4): 305-318, 2023 04.
Article in English | MEDLINE | ID: covidwho-2279840

ABSTRACT

Invasive fungal infections are an increasing threat to human health. Of recent concern is the emergence of influenza- or SARS-CoV-2-virus-associated invasive fungal infections. Understanding acquired susceptibilities to fungi requires consideration of the collective and newly explored roles of adaptive, innate, and natural immunity. Neutrophils are known to provide host resistance, but new concepts are emerging that implicate innate antibodies, the actions of specialized B1 B cell subsets, and B cell-neutrophil crosstalk in mediating antifungal host resistance. Based on emerging evidence, we propose that virus infections impact on neutrophil and innate B cell resistance against fungi, leading to invasive infections. These concepts provide novel approaches to developing candidate therapeutics with the aim of restoring natural and humoral immunity and boosting neutrophil resistance against fungi.


Subject(s)
COVID-19 , Invasive Fungal Infections , Mycoses , Humans , SARS-CoV-2 , Fungi , Immunity, Innate
13.
Adv Sci (Weinh) ; 10(10): e2205781, 2023 04.
Article in English | MEDLINE | ID: covidwho-2279755

ABSTRACT

Invasive fungal infections are a growing public health threat. As fungi become increasingly resistant to existing drugs, new antifungals are urgently needed. Here, it is reported that 405-nm-visible-light-activated synthetic molecular machines (MMs) eliminate planktonic and biofilm fungal populations more effectively than conventional antifungals without resistance development. Mechanism-of-action studies show that MMs bind to fungal mitochondrial phospholipids. Upon visible light activation, rapid unidirectional drilling of MMs at ≈3 million cycles per second (MHz) results in mitochondrial dysfunction, calcium overload, and ultimately necrosis. Besides their direct antifungal effect, MMs synergize with conventional antifungals by impairing the activity of energy-dependent efflux pumps. Finally, MMs potentiate standard antifungals both in vivo and in an ex vivo porcine model of onychomycosis, reducing the fungal burden associated with infection.


Subject(s)
Antifungal Agents , Calcium , Animals , Swine , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Antifungal Agents/metabolism , Calcium/metabolism , Fungi/metabolism
14.
PLoS One ; 18(3): e0279118, 2023.
Article in English | MEDLINE | ID: covidwho-2269932

ABSTRACT

The Covid-19 associated mucormycosis (CAM) is an emerging disease affecting immunocompromised patients. Prevention of such infections using probiotics and their metabolites persist as effective therapeutic agents. Therefore, the present study emphasizes on assessment of their efficacy and safety. Samples from different sources like human milk, honey bee intestine, toddy, and dairy milk were collected, screened and characterized for potential probiotic lactic acid bacteria (LAB) and their metabolites to be used as effective antimicrobial agents to curtail CAM. Three isolates were selected based on probiotic properties and characterized as Lactobacillus pentosus BMOBR013, Lactobacillus pentosus BMOBR061 and Pediococcus acidilactici BMOBR041 by 16S rRNA sequencing and MALDI TOF-MS. The antimicrobial activity against standard bacterial pathogens showed ˃9 mm zone of inhibition. Furthermore, the antifungal activity of three isolates was tested against Aspergillus flavus MTCC 2788, Fusarium oxysporum, Candida albicans and Candida tropicalis where the results showed significant inhibition of each fungal strain. Further studies were carried out on lethal fungal pathogens like Rhizopus sp. and two Mucor sp. which are associated with post Covid-19 infection in immunosuppressed diabetic patients. Our studies on CAM inhibitory effect of LAB revealed the efficient inhibition against Rhizopus sp. and two Mucor sp. The cell free supernatants of three LAB showed varied inhibitory activity against these fungi. Following the antimicrobial activity, the antagonistic metabolite 3-Phenyllactic acid (PLA) in culture supernatant was quantified and characterized by HPLC and LC-MS using standard PLA (Sigma Aldrich). The isolate L. pentosus BMOBR013 produced highest PLA (0.441 g/L), followed by P. acidilactici BMOBR041 (0.294 g/L) and L. pentosus BMOBR061 (0.165 g/L). The minimum inhibitory concentration of HPLC eluted PLA on the Rhizopus sp. and two Mucor sp. was found to be 180 mg/ml which was further confirmed by inhibition of total mycelia under live cell imaging microscope.


Subject(s)
Anti-Infective Agents , COVID-19 , Lactobacillales , Mucormycosis , Probiotics , Humans , Animals , Bees/genetics , Mucormycosis/drug therapy , RNA, Ribosomal, 16S/genetics , Lactobacillales/genetics , Fungi/genetics , Probiotics/pharmacology , Polyesters
15.
Emerg Infect Dis ; 28(10): 2091-2095, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2287570

ABSTRACT

We report Mycetohabitans rhizoxinica bacteremia in a 65-year-old woman in California, USA, who was undergoing chimeric antigen receptor T-cell therapy for multiple myeloma. Acute brain infarction and pneumonia developed; Rhizopus microsporus mold was isolated from tracheal suction. Whole-genome sequencing confirmed bacteria in blood as genetically identical to endofungal bacteria inside the mold.


Subject(s)
Bacteremia , Burkholderia , Mucormycosis , Receptors, Chimeric Antigen , Respiratory Tract Infections , Aged , Burkholderiaceae , Fungi , Humans , Mucormycosis/diagnosis , Rhizopus/genetics , Symbiosis
16.
Annu Rev Immunol ; 40: 121-141, 2022 04 26.
Article in English | MEDLINE | ID: covidwho-2253906

ABSTRACT

Invasive fungal diseases are rare in individuals with intact immunity. This, together with the fact that there are only a few species that account for most mycotic diseases, implies a remarkable natural resistance to pathogenic fungi. Mammalian immunity to fungi rests on two pillars, powerful immune mechanisms and elevated temperatures that create a thermal restriction zone for most fungal species. Conditions associated with increased susceptibility generally reflect major disturbances of immune function involving both the cellular and humoral innate and adaptive arms, which implies considerable redundancy in host defense mechanisms against fungi. In general, tissue fungal invasion is controlled through either neutrophil or granulomatous inflammation, depending on the fungal species. Neutrophils are critical against Candida spp. and Aspergillus spp. while macrophages are essential for controlling mycoses due to Cryptococcus spp., Histoplasma spp., and other fungi. The increasing number of immunocompromised patients together with climate change could significantly increase the prevalence of fungal diseases.


Subject(s)
Mycoses , Animals , Fungi , Humans , Immunity, Innate , Immunocompromised Host , Macrophages , Mammals
17.
Nat Rev Microbiol ; 21(4): 211-212, 2023 04.
Article in English | MEDLINE | ID: covidwho-2259266
18.
J Microbiol Immunol Infect ; 56(3): 442-454, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2241580

ABSTRACT

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.


Subject(s)
COVID-19 , Mucormycosis , Pulmonary Aspergillosis , Humans , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Pandemics , COVID-19/complications , Fungi
19.
J Med Microbiol ; 72(2)2023 Feb.
Article in English | MEDLINE | ID: covidwho-2241170

ABSTRACT

Introduction. Mucormycosis is a severe angio-invasive fungal infection caused by mucormycetes, a group of fungi that are ubiquitous in the environment. The incidence of mucormycosis has been surging rapidly due to the global corona virus disease 2019 (COVID-19) pandemic.Gap Statement. The complete picture of the causative fungi associated with mucormycosis and their phylogenetic relationships are not well defined.Aim. This meta-analysis aimed to collate all confirmed fungal pathogens that cause mucormycosis, and assess their taxonomic relationships.Methodology. All types of articles in the PubMed database that report fungi as a cause of mucormycosis were reviewed. We summarized the fungal morphological characteristic up to the genus level. The internal transcribed spacer (ITS) nucleotide sequences of these fungi were retrieved from the National Center for Biotechnology Information (NCBI) and UNITE databases whenever available, and multiple sequence analysis was conducted using Clustal W. The phylogenetic tree was constructed using mega version 7.Results. Forty-seven fungal species were identified as pathogens causing mucormycosis in humans. Thirty-two fungal species were phylogenetically grouped into three clades, and it was evident that the ITS sequences have well-conserved regions in all clades, especially from the 400th to 500th base pairs.Conclusion. The findings of this work contribute to the descriptive data for fungi that cause mucormycosis, emphasizing the need for robust phylogenetic approaches when identifying clinical isolates from infected patients.


Subject(s)
COVID-19 , Mucormycosis , Humans , Phylogeny , Fungi , DNA, Ribosomal Spacer/genetics , DNA, Fungal/genetics , DNA, Fungal/analysis
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