Interactions of Both Pathogenic and Nonpathogenic CUG Clade Candida Species with Macrophages Share a Conserved Transcriptional Landscape

Common Cause ◽

Content Type ◽

Life Threatening ◽

Transcriptional Landscape

Candidiasis is a major fungal infection by Candida species, causing life-threatening invasive disease in immunocompromised patients. C. albicans , which is adapted to commensalism of human mucosae, is the most common cause. While several other species cause infection, most are less prevalent or less virulent.

Efficacy of Liposomal Amphotericin B and Posaconazole in Intratracheal Models of Murine Mucormycosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00313-13 ◽

2013 ◽

Vol 57 (7) ◽

pp. 3340-3347 ◽

Cited By ~ 33

Author(s):

Guanpingsheng Luo ◽

Teclegiorgis Gebremariam ◽

Hongkyu Lee ◽

Samuel W. French ◽

Nathan P. Wiederhold ◽

...

Keyword(s):

Fungal Infection ◽

Amphotericin B ◽

Liposomal Amphotericin ◽

Intratracheal Instillation ◽

Cortisone Acetate ◽

Liposomal Amphotericin B ◽

Content Type ◽

Pulmonary Mucormycosis ◽

ABSTRACTMucormycosis is a life-threatening fungal infection almost uniformly affecting diabetics in ketoacidosis or other forms of acidosis and/or immunocompromised patients. Inhalation ofMucoralesspores provides the most common natural route of entry into the host. In this study, we developed an intratracheal instillation model of pulmonary mucormycosis that hematogenously disseminates into other organs using diabetic ketoacidotic (DKA) or cyclophosphamide-cortisone acetate-treated mice. Various degrees of lethality were achieved for the DKA or cyclophosphamide-cortisone acetate-treated mice when infected with different clinical isolates ofMucorales. In both DKA and cyclophosphamide-cortisone acetate models, liposomal amphotericin B (LAmB) or posaconazole (POS) treatments were effective in improving survival, reducing lungs and brain fungal burdens, and histologically resolving the infection compared with placebo. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies, and evaluate drug efficacies against life-threateningMucoralesinfections.

Pulmonary Mucormycosis: An Emerging Infection

Case Reports in Pulmonology ◽

10.1155/2012/120809 ◽

2012 ◽

Vol 2012 ◽

pp. 1-3 ◽

Cited By ~ 4

Author(s):

Mohammed Muqeetadnan ◽

Ambreen Rahman ◽

Syed Amer ◽

Salman Nusrat ◽

Syed Hassan ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fungal Infection ◽

Diabetic Patient ◽

Patient Survival ◽

Early Recognition ◽

Delay In Diagnosis ◽

Pulmonary Mucormycosis ◽

Aggressive Management ◽

Mucormycosis is a rare, but emerging, life-threatening, rapidly progressive, angioinvasive fungal infection that usually occurs in immunocompromised patients. We present a case of pulmonary mucormycosis in a diabetic patient who was on chronic steroid therapy for ulcerative colitis. Early recognition of this diagnosis, along with aggressive management, is critical to effective therapy and patient survival. The delay in diagnosis of this rapidly progressive infection can result in mortality.

Pseudomonas aeruginosa AlgU Contributes to Posttranscriptional Activity by IncreasingrsmAExpression in amucA22Strain

Journal of Bacteriology ◽

10.1128/jb.00133-16 ◽

2016 ◽

Vol 198 (13) ◽

pp. 1812-1826 ◽

Cited By ~ 11

Author(s):

Sean D. Stacey ◽

Christopher L. Pritchett

Keyword(s):

Pseudomonas Aeruginosa ◽

Biofilm Formation ◽

Laboratory Strain ◽

Chronic Infections ◽

Rnase Protection ◽

Content Type ◽

Mutant Strains ◽

Life Threatening ◽

Severe Infections

ABSTRACTPseudomonas aeruginosathrives in multiple environments and is capable of causing life-threatening infections in immunocompromised patients. RsmA is a posttranscriptional regulator that controls virulence factor production and biofilm formation. In this study, we investigated the expression and activity ofrsmAand the protein that it encodes, RsmA, inP. aeruginosamucAmutant strains, which are common in chronic infections. We determined that AlgU regulates a previously unknownrsmApromoter inP. aeruginosa. Western blot analysis confirmed that AlgU controlsrsmAexpression in both a laboratory strain and a clinical isolate. RNase protection assays confirmed the presence of tworsmAtranscripts and suggest that RpoS and AlgU regulatersmAexpression. Due to the increased amounts of RsmA inmucAmutant strains, a translational leader fusion of the RsmA target,tssA1, was constructed and tested inmucA,algU,retS,gacA, andrsmAmutant backgrounds to examine posttranscriptional activity. From these studies, we determined that RsmA is active inmucA22mutants, suggesting a role for RsmA inmucAmutant strains. Taken together, we have demonstrated that AlgU controlsrsmAtranscription and is responsible for RsmA activity inmucAmutant strains. We propose that RsmA is active inP. aeruginosamucAmutant strains and that RsmA also plays a role in chronic infections.IMPORTANCEP. aeruginosacauses severe infections in immunocompromised patients. The posttranscriptional regulator RsmA is known to control virulence and biofilm formation. We identify a newrsmApromoter and determine that AlgU is important in the control ofrsmAexpression. MutantmucAstrains that are considered mucoid were used to confirm increasedrsmAexpression from the AlgU promoter. We demonstrate, for the first time, that there is RsmA activity in mucoidP. aeruginosastrains. Our work suggests that RsmA may play a role during chronic infections as well as acute infections.

Extracellular Vesicles from Aspergillus flavus Induce M1 Polarization In Vitro

mSphere ◽

10.1128/msphere.00190-20 ◽

2020 ◽

Vol 5 (3) ◽

Cited By ~ 5

Author(s):

Verônica S. Brauer ◽

André M. Pessoni ◽

Tamires A. Bitencourt ◽

Renato G. de Paula ◽

Liliana de Oliveira Rocha ◽

...

Keyword(s):

Fungal Infection ◽

Extracellular Vesicles ◽

Aspergillus Flavus ◽

Crucial Role ◽

Galleria Mellonella ◽

Biologically Active ◽

Common Cause ◽

Content Type ◽

M1 Macrophage

ABSTRACT Aspergillus flavus, a ubiquitous and saprophytic fungus, is the second most common cause of aspergillosis worldwide. Several mechanisms contribute to the establishment of the fungal infection. Extracellular vesicles (EVs) have been described as “virulence factor delivery bags” in several fungal species, demonstrating a crucial role during the infection. In this study, we evaluated production of A. flavus EVs and their immunomodulatory functions. We verified that A. flavus EVs induce macrophages to produce inflammatory mediators, such as nitric oxide, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-1β. Furthermore, the A. flavus EVs enhance phagocytosis and killing by macrophages and induce M1 macrophage polarization in vitro. In addition, a prior inoculation of A. flavus EVs in Galleria mellonella larvae resulted in a protective effect against the fungal infection. Our findings suggest that A. flavus EVs are biologically active and affect the interaction between A. flavus and host immune cells, priming the innate immune system to eliminate the fungal infection. Collectively, our results suggest that A. flavus EVs play a crucial role in aspergillosis. IMPORTANCE Immunocompromised patients are susceptible to several fungal infections. The genus Aspergillus can cause increased morbidity and mortality. Developing new therapies is essential to understand the fungal biology mechanisms. Fungal EVs carry important virulence factors, thus playing pivotal roles in fungal pathophysiology. No study to date has reported EV production by Aspergillus flavus, a fungus considered to be the second most common cause of aspergillosis and relevant food contaminator found worldwide. In this study, we produced A. flavus EVs and evaluated the in vitro immunomodulatory effects of EVs on bone marrow-derived macrophages (BMDMs) and in vivo effects in a Galleria mellonella model.

InvasiveBacillus cereusInfection in a Renal Transplant Patient: A Case Report and Review

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2012/461020 ◽

2012 ◽

Vol 23 (4) ◽

pp. e109-e110 ◽

Cited By ~ 2

Author(s):

Susan John ◽

John Neary ◽

Christine H Lee

Keyword(s):

Case Report ◽

Renal Transplant ◽

Renal Transplant Patient ◽

Transplant Patient ◽

Food Poisoning ◽

Specific Treatment ◽

Gastrointestinal Diseases ◽

Invasive Disease ◽

Common Cause

Bacillus cereusis a common cause of gastrointestinal diseases. The majority of individuals withB cereus-related food poisoning recover without any specific treatment. It can, however, rarely cause invasive disease in immunocompromised patients.

COVID-19 Associated Rhino-Orbital Mucormycosis Complicated by Gangrenous and Bone Necrosis—A Case Report from Honduras

Vaccines ◽

10.3390/vaccines9080826 ◽

2021 ◽

Vol 9 (8) ◽

pp. 826

Author(s):

Elsa Yolanda Palou ◽

María Auxiliadora Ramos ◽

Emec Cherenfant ◽

Adoni Duarte ◽

Itzel Carolina Fuentes-Barahona ◽

...

Keyword(s):

Risk Factors ◽

Case Report ◽

Early Diagnosis ◽

Fungal Infection ◽

Invasive Fungal Infection ◽

Bone Necrosis ◽

Inappropriate Use ◽

Prompt Treatment ◽

Background: Mucormycosis is a life-threatening invasive fungal infection most commonly observed in immunocompromised patients. Throughout the COVID-19 pandemic, a growing number of Mucorales associated infections, now termed COVID-19 associated mucormycosis (CAM), have been reported. Despite an increase in fatality reports, no cases of rhino-orbital CAM complicated with gangrenous bone necrosis have been described in the literature to date. Case: A 56-year-old male with a recent COVID-19 diagnosis developed rhino-orbital mucormycosis after 22 days of treatment with dexamethasone. Cultures and histopathological assessment of tissue biopsy confirmed the diagnosis. The patient survived after treatment with amphotericin B. Conclusions: Mucormycosis is an invasive fungal infection affecting mostly immunocompromised patients. Along with the COVID-19 pandemic, the inappropriate use of steroids, in addition to concurrent risk factors, such as diabetes, has led to an increase in the occurrence of these devastating mycoses, leading to the development of severe presentations and complications, as observed in many cases. Early diagnosis and prompt treatment are crucial in order to avoid dissemination and fatal outcomes.

CRISPR-Mediated Transcriptional Repression in Toxoplasma gondii

mSphere ◽

10.1128/msphere.00474-21 ◽

2021 ◽

Author(s):

Benedikt M. Markus ◽

Elizabeth A. Boydston ◽

Sebastian Lourido

Keyword(s):

Toxoplasma Gondii ◽

Transcriptional Repression ◽

Functional Annotation ◽

Intracellular Parasite ◽

Content Type ◽

Fetal Abnormalities ◽

Health Implications ◽

Life Threatening ◽

Eye Lesions

Toxoplasma gondii is a ubiquitous intracellular parasite of humans and animals that causes life-threatening disease in immunocompromised patients, fetal abnormalities when contracted during gestation, and recurrent eye lesions in some patients. Despite its health implications, about half of the Toxoplasma genome still lacks functional annotation.

Detection of Pneumocystis jirovecii by Quantitative PCR To Differentiate Colonization and Pneumonia in Immunocompromised HIV-Positive and HIV-Negative Patients

Journal of Clinical Microbiology ◽

10.1128/jcm.03174-15 ◽

2016 ◽

Vol 54 (6) ◽

pp. 1487-1495 ◽

Cited By ~ 57

Author(s):

T. Fauchier ◽

L. Hasseine ◽

M. Gari-Toussaint ◽

V. Casanova ◽

P. M. Marty ◽

...

Keyword(s):

Hiv Infection ◽

Quantitative Pcr ◽

Pneumocystis Jirovecii ◽

Hiv Positive ◽

Infection Status ◽

Content Type ◽

Fungal Burden ◽

Life Threatening ◽

Hiv Negative

Pneumocystisjiroveciipneumonia (PCP) is an acute and life-threatening lung disease caused by the fungusPneumocystis jirovecii. The presentation of PCP in HIV-positive patients is well-known and consists of a triad of dyspnea, fever, and cough, whereas the presentation of PCP in HIV-negative patients is atypical and consists of a sudden outbreak, O2desaturation, and a rapid lethal outcome without therapy. Despite the availability of direct and indirect identification methods, the diagnosis of PCP remains difficult. The cycle threshold (CT) values obtained by quantitative PCR (qPCR) allow estimation of the fungal burden. The more elevated that the fungal burden is, the higher the probability that the diagnosis is pneumonia. The purposes of the present study were to evaluate theCTvalues to differentiate colonization and pneumonia in a population of immunocompromised patients overall and patients stratified on the basis of their HIV infection status. Testing of bronchoalveolar lavage (BAL) fluid samples from the whole population of qPCR-positive patients showed a meanCTvalue for patients with PCP of 28 (95% confidence interval [CI], 26 to 30) and a meanCTvalue for colonized patients of 35 (95% CI, 34 to 36) (P< 10−3). For the subgroup of HIV-positive patients, we demonstrated that aCTvalue below 27 excluded colonization and aCTvalue above 30 excluded PCP with a specificity of 100% and a sensitivity of 80%, respectively. In the subgroup of HIV-negative patients, we demonstrated that aCTvalue below 31 excluded colonization and aCTvalue above 35 excluded PCP with a specificity of 80% and a sensitivity of 80%, respectively. Thus, qPCR of BAL fluid samples is an important tool for the differentiation of colonization and pneumonia inP. jirovecii-infected immunocompromised patients and patients stratified on the basis of HIV infection status with differentCTvalues.

Genome Sequence for Candida albicans Clinical Oral Isolate 529L

Microbiology Resource Announcements ◽

10.1128/mra.00554-19 ◽

2019 ◽

Vol 8 (25) ◽

Cited By ~ 3

Author(s):

Christina A. Cuomo ◽

Saranna Fanning ◽

Sharvari Gujja ◽

Qiandong Zeng ◽

Julian R. Naglik ◽

...

Keyword(s):

Candida Albicans ◽

Fungal Infection ◽

Genome Sequence ◽

Sequence Assembly ◽

Genetic Studies ◽

Common Cause ◽

Content Type ◽

Genome Sequence Assembly

The diploid heterozygous yeast Candida albicans is the most common cause of fungal infection. Here, we report the genome sequence assembly of the clinical oral isolate 529L. As this isolate grows as a commensal, this genome will serve as a reference for experimental and genetic studies of mucosal colonization.

Unraveling Caspofungin Resistance in Cryptococcus neoformans

mBio ◽

10.1128/mbio.00156-21 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Nicolas Papon ◽

Gustavo H. Goldman

Keyword(s):

Cell Wall ◽

Cryptococcus Neoformans ◽

Posttranscriptional Regulation ◽

Fungal Infections ◽

Cell Wall Biosynthesis ◽

Efficient Treatment ◽

Content Type ◽

Great Hope ◽

ABSTRACT Cryptococcus neoformans is a basidiomycetous yeast responsible for hundreds of thousands of deaths a year and is particularly threatening in immunocompromised patients. There are few families of antifungals that are available to fight fungal infections, and the unique efficient treatment for the most deadly cerebral forms of cryptococcosis is based on a combination of 5-fluorocytosine and amphotericin B. The toxicities of both compounds are elevated, and more therapeutic options are urgently needed for better management of life-threatening cryptococcosis. The newest class of antifungals, i.e., echinocandins, has initially led to great hope. Unfortunately, C. neoformans was rapidly confirmed to be naturally resistant to these molecules, notably caspofungin. In this respect, we discuss here the recent key findings of the Panepinto research group published in mBio (M. C. Kalem et al., mBio 12:e03225-20, 2021, https://doi:10.1128/mBio.03225-20) that provide an unprecedented view of how C. neoformans regulates caspofungin resistance through a complex posttranscriptional regulation of cell wall biosynthesis genes.