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Pathogens
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Opportunistic Fungal Infections
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Opportunistic Fungal Infections

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Fungal Pathogens".

Deadline for manuscript submissions: closed (1 July 2023) | Viewed by 21195

Special Issue Editors

Dr. María Guadalupe Frías-De-León

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Guest Editor
Hospital Regional de Alta Especialidad de Ixtapaluca, Carretera Federal México-Puebla Km. 34.5, Pueblo de Zoquiapan, Ixtapaluca 56530, Mexico
Interests: Candida; molecular diagnosis; antifungal resistance; opportunistic fungi
Special Issues, Collections and Topics in MDPI journals
Dr. María del Rocío Reyes Montes

E-Mail Website
Guest Editor
Departamento de Microbiología-Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico
Interests: molecular epidemiology; molecular diagnostic; molecular markers; aspergillosis; coccidioidomicosis; dermatophytosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The frequency of opportunistic mycoses is increasing due to the increase in the susceptible population. Among the predisposing factors for the development of these fungal infections is immunosuppression that is associated with extensive surgeries, organ transplants, antineoplastic chemotherapy, parenteral nutrition, treatment with broad-spectrum antibiotics or steroids, among others. Some species of the genera Candida, Aspergillus, Cryptococcus, Mucor, and Pneumocystis carinii, are responsible for this, according to the etiology of opportunistic infections. The mortality rate of these fungal infections is high and is associated, in part, with late diagnosis, which leads to the inadequate treatment of patients. Although considerable progress has been made in both diagnosis and treatment, opportunistic fungal infections will result in significant problems, such as antifungal resistance and the appearance of new species that pose the challenge of establishing a specific diagnosis that allows the prognosis of the patient to be improved. The aim of this Special Issue, “Opportunistic Fungal Infections”, is to show the current state of the tools for diagnosis, treatment, and prevention as well as aspects of the epidemiology and pathogenesis of these fungi, mainly the virulence factors of opportunistic fungal infections. Therefore, we recommend the submission of original research articles, case studies or brief reports, and reviews as well as opinion pieces on these points.

Dr. María Guadalupe Frías-De-León
Dr. María del Rocío Reyes Montes
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • opportunistic mycosis
  • virulence factors
  • molecular diagnosis
  • antifungal treatment
  • antifungal resistance

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Published Papers (7 papers)

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Research

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9 pages, 279 KiB  
Communication
Potential Inhibitory Effect of Miltefosine against Terbinafine-Resistant Trichophyton indotineae
by Iman Haghani, Javad Akhtari, Zahra Yahyazadeh, Amirreza Espahbodi, Firoozeh Kermani, Javad Javidnia, Mohammad Taghi Hedayati, Tahereh Shokohi, Hamid Badali, Ali Rezaei-Matehkolaei, Seyed Reza Aghili, Ahmed Al-Rawahi, Ahmed Al-Harrasi, Mahdi Abastabar and Abdullah M. S. Al-Hatmi
Pathogens 2023, 12(4), 606; https://doi.org/10.3390/pathogens12040606 - 17 Apr 2023
Cited by 8 | Viewed by 1862
Abstract
Several prolonged and significant outbreaks of dermatophytosis caused by Trichophyton indotineae, a new emerging terbinafine-resistant species, have been ongoing in India in recent years, and have since spread to various countries outside Asia. Miltefosine, an alkylphosphocholine, is the most recently approved drug [...] Read more.
Several prolonged and significant outbreaks of dermatophytosis caused by Trichophyton indotineae, a new emerging terbinafine-resistant species, have been ongoing in India in recent years, and have since spread to various countries outside Asia. Miltefosine, an alkylphosphocholine, is the most recently approved drug for the treatment of both visceral and cutaneous leishmaniasis. Miltefosine in vitro activity against terbinafine-resistant and susceptible T. mentagrophytes/T. interdigitale species complex, including T. indotineae, is limited. The current study aimed to assess miltefosine’s in vitro activity against dermatophyte isolates, which are the most common causes of dermatophytosis. Miltefosine, terbinafine, butenafine, tolnaftate, and itraconazole susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution methods (CLSI M38-A3) against 40 terbinafine-resistant T. indotineae isolates and 40 terbinafine-susceptible T. mentagrophytes/T. interdigitale species complex isolates. Miltefosine had MIC ranges of 0.063–0.5 µg/mL and 0.125–0.25 µg/mL against both terbinafine-resistant and susceptible isolates. In terbinafine-resistant isolates, the MIC50 and MIC90 were 0.125 µg/mL and 0.25 µg/mL, respectively, and 0.25 µg/mL in susceptible isolates. Miltefosine had statistically significant differences in MIC results when compared to other antifungal agents (p-value 0.05) in terbinafine-resistant strains. Accordingly, the findings suggest that miltefosine has a potential activity for treating infections caused by terbinafine-resistant T. indotineae. However, further studies are needed to determine how well this in vitro activity translates into in vivo efficacy. Full article
(This article belongs to the Special Issue Opportunistic Fungal Infections)
15 pages, 567 KiB  
Article
Uncovering the Yeast Diversity in the Female Genital Tract: An Exploration of Spatial Distribution and Antifungal Resistance
by Mariana Zagalo Fernandes, Cátia Filipa Caetano, Carlos Gaspar, Ana Sofia Oliveira, Rita Palmeira-de-Oliveira, José Martinez-de-Oliveira, Joana Rolo and Ana Palmeira-de-Oliveira
Pathogens 2023, 12(4), 595; https://doi.org/10.3390/pathogens12040595 - 14 Apr 2023
Cited by 5 | Viewed by 3621
Abstract
Candida albicans is the leading cause of vulvovaginal yeast infections; however, other species are becoming relevant in this niche. The spatial distribution of these fungi in the female genital tract remains poorly understood. In this study, swab samples were collected from 33 patients, [...] Read more.
Candida albicans is the leading cause of vulvovaginal yeast infections; however, other species are becoming relevant in this niche. The spatial distribution of these fungi in the female genital tract remains poorly understood. In this study, swab samples were collected from 33 patients, first from the anterior vulva and then from the upper third and right lateral wall of the vagina: 16 were with symptoms of vulvovaginal candidiasis and 17 were without characteristic symptoms; furthermore, the genus and species of each isolate were identified. In vitro susceptibility testing for fluconazole and clotrimazole was performed for all isolates. Candida albicans was the most common species (63.6%), followed by Rhodotorula spp. (51.5%), and then Candida parapsilosis (15.2%). Rhodotorula spp. and C. parapsilosis were more commonly associated with colonization, and C. albicans with infection. Rhodotorula spp. isolates presented a low susceptibility to fluconazole, with the MIC ranging from 32 to >64 µg/mL. Differences in susceptibility to fluconazole and clotrimazole between the pairs of vaginal and vulvar isolates were found for Candida albicans, Rhodotorula spp., and Nakaseomyces glabratus. The results suggest that different niches may impact the susceptibility profiles of the isolates, as well as their different clinical behaviors. Full article
(This article belongs to the Special Issue Opportunistic Fungal Infections)
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13 pages, 2562 KiB  
Article
Expression of Cytokine Profiles in Human THP-1 Cells during Phase Transition of Talaromyces marneffei
by Fangyi Shu, Patcharin Thammasit, Kritsada Pruksaphon, Joshua D. Nosanchuk and Sirida Youngchim
Pathogens 2022, 11(12), 1465; https://doi.org/10.3390/pathogens11121465 - 2 Dec 2022
Cited by 4 | Viewed by 2509
Abstract
Talaromyces marneffei, a dimorphic fungus, exhibits temperature-dependent growth, existing in a filamentous form at 25 °C and as a yeast at 37 °C. Several studies have highlighted the important roles of macrophages in defense against T. marneffei infection. However, the immune responses [...] Read more.
Talaromyces marneffei, a dimorphic fungus, exhibits temperature-dependent growth, existing in a filamentous form at 25 °C and as a yeast at 37 °C. Several studies have highlighted the important roles of macrophages in defense against T. marneffei infection. However, the immune responses to the interaction of macrophages with T. marneffei cells during phase transition require further investigation. This study reports the expression of cytokine profiles in human THP-1 cells during infection by T. marneffei. THP-1 cells were infected with T. marneffei conidia at different multiplicity of infections (MOIs). Surviving conidia transformed into yeasts after phagocytosis by macrophages, and the number of yeasts gradually increased over 36 h. The transcription and secretion levels of pro- and anti-inflammatory cytokines were examined at different times by qRT-PCR and ELISA. Transcription levels of IL-8, IL-12, IL-1β, and TNF-α increased significantly at 12 or 24 h and then slightly decreased at 36 h. In contrast, the transcription levels of IL-6, IL-10, and TGF-β gradually increased at all MOIs. The levels of IL-6 and IL-10 secretion corresponded to their levels of transcription. These results indicated that as the number of intracellular yeasts increased, the infected macrophages first underwent slight M1 polarization before shifting to M2 polarization. This polarization transition was confirmed by the fungicidal ability and the expression of macrophage surface markers. By inducing the M2-type polarization of macrophages, the intracellular T. marneffei cells can successfully evade the immune response. Our study provides a novel insight into the immune characterization during the transition of T. marneffei infection and could further contribute to possible diagnostic and therapeutic interventions for this infection. Full article
(This article belongs to the Special Issue Opportunistic Fungal Infections)
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Review

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15 pages, 697 KiB  
Review
Addressing Microbial Resistance Worldwide: Challenges over Controlling Life-Threatening Fungal Infections
by Leonardo Martins-Santana, Caroline Patini Rezende, Antonio Rossi, Nilce Maria Martinez-Rossi and Fausto Almeida
Pathogens 2023, 12(2), 293; https://doi.org/10.3390/pathogens12020293 - 10 Feb 2023
Cited by 16 | Viewed by 3884
Abstract
Fungal infections are a serious global concern because of their ability to spread and colonize host tissues in immunocompromised individuals. Such infections have been frequently reported worldwide and are currently gaining clinical research relevance owing to their resistant character, representing a bottleneck in [...] Read more.
Fungal infections are a serious global concern because of their ability to spread and colonize host tissues in immunocompromised individuals. Such infections have been frequently reported worldwide and are currently gaining clinical research relevance owing to their resistant character, representing a bottleneck in treating affected people. Resistant fungi are an emergent public health threat. The upsurge of such pathogens has led to new research toward unraveling the destructive potential evoked by these species. Some fungi—grouped into Candida, Aspergillus, and Cryptococcus—are causative agents of severe and systemic infections. They are associated with high mortality rates and have recently been described as sources of coinfection in COVID-hospitalized patients. Despite the efforts to elucidate the challenges of colonization, dissemination, and infection severity, the immunopathogenesis of fungal diseases remains a pivotal characteristic in fungal burden elimination. The struggle between the host immune system and the physiological strategies of the fungi to maintain cellular viability is complex. In this brief review, we highlight the relevance of drug resistance phenotypes in fungi of clinical significance, taking into consideration their physiopathology and how the scientific community could orchestrate their efforts to avoid fungal infection dissemination and deaths. Full article
(This article belongs to the Special Issue Opportunistic Fungal Infections)
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13 pages, 516 KiB  
Review
Aspergillus-SARS-CoV-2 Coinfection: What Is Known?
by Carlos Alberto Castro-Fuentes, María del Rocío Reyes-Montes, María Guadalupe Frías-De-León, Omar E. Valencia-Ledezma, Gustavo Acosta-Altamirano and Esperanza Duarte-Escalante
Pathogens 2022, 11(11), 1227; https://doi.org/10.3390/pathogens11111227 - 25 Oct 2022
Cited by 7 | Viewed by 2688
Abstract
COVID-19-associated pulmonary aspergillosis (CAPA) has had a high incidence. In addition, it has been associated with prolonged hospital stays, as well as several predisposing risk factors, such as fungal factors (nosocomial organism, the size of the conidia, and the ability of the Aspergillus [...] Read more.
COVID-19-associated pulmonary aspergillosis (CAPA) has had a high incidence. In addition, it has been associated with prolonged hospital stays, as well as several predisposing risk factors, such as fungal factors (nosocomial organism, the size of the conidia, and the ability of the Aspergillus spp. of colonizing the respiratory tract), environmental factors (remodeling in hospitals, use of air conditioning and negative pressure in intensive care units), comorbidities, and immunosuppressive therapies. In addition to these factors, SARS-CoV-2 per se is associated with significant dysfunction of the patient’s immune system, involving both innate and acquired immunity, with reduced CD4+ and CD8+ T cell counts and cytokine storm. Therefore, this review aims to identify the factors influencing the fungus so that coinfection with SARS-CoV-2 can occur. In addition, we analyze the predisposing factors in the fungus, host, and the immune response alteration due to the pathogenicity of SARS-CoV-2 that causes the development of CAPA. Full article
(This article belongs to the Special Issue Opportunistic Fungal Infections)
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Other

Jump to: Research, Review

25 pages, 1394 KiB  
Systematic Review
Lomentospora prolificans Disseminated Infections: A Systematic Review of Reported Cases
by Afroditi Konsoula, Aris P. Agouridis, Lamprini Markaki, Constantinos Tsioutis and Nikolaos Spernovasilis
Pathogens 2023, 12(1), 67; https://doi.org/10.3390/pathogens12010067 - 31 Dec 2022
Cited by 8 | Viewed by 3693
Abstract
Background: Lomentospora prolificans, a rare, highly virulent filamentous fungus with high rates of intrinsic resistance to antifungals, has been associated with different types of infections in immunocompromised as well as immunocompetent individuals. Objective: To systematically address all relevant evidence regarding L. prolificans [...] Read more.
Background: Lomentospora prolificans, a rare, highly virulent filamentous fungus with high rates of intrinsic resistance to antifungals, has been associated with different types of infections in immunocompromised as well as immunocompetent individuals. Objective: To systematically address all relevant evidence regarding L. prolificans disseminated infections in the literature. Methods: We searched Medline via PubMed and Scopus databases through July 2022. We performed a qualitative synthesis of published articles reporting disseminated infections from L. prolificans in humans. Results: A total of 87 studies describing 142 cases were included in our systematic review. The pathogen was most frequently reported in disseminated infections in Spain (n = 47), Australia (n = 33), the USA (n = 21), and Germany (n = 10). Among 142 reported cases, 48.5% were males. Underlying conditions identified for the majority of patients included malignancy (72.5%), hemopoietic stem cell transplantation (23.2%), solid organ transplantation (16%), and AIDS (2%). Lungs, central nervous system, skin, eyes, heart and bones/joints were the most commonly affected organs. Neutropenia was recorded in 52% of patients. The mortality rate was as high as 87.3%. Conclusions: To the best of our knowledge, this is the first systematic review conducted on disseminated infections due to this rare microorganism. Physicians should be aware that L. prolificans can cause a diversity of infections with high mortality and primarily affects immunocompromised and neutropenic patients. Full article
(This article belongs to the Special Issue Opportunistic Fungal Infections)
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7 pages, 567 KiB  
Case Report
Late Diagnosis of Disseminated Sporothrix brasiliensis Infection with Bone Marrow Involvement in an HIV-Negative Patient
by Vanessa Caroline Randi Magalhães, Salene Angelini Colombo, Gustavo José Cota Freitas, Alexandre Sampaio Moura, Flávia Cardoso Lopez Vieira, Ana Cláudia Lyon, Maria Isabel Azevedo, Nalu Teixeira de Aguiar Peres and Daniel Assis Santos
Pathogens 2022, 11(12), 1516; https://doi.org/10.3390/pathogens11121516 - 10 Dec 2022
Cited by 3 | Viewed by 1857
Abstract
Sporotrichosis is a fungal disease that causes symptoms similar to those of other infectious and non-infectious diseases, making diagnosis difficult and challenging. Here, we report a case of an HIV-negative patient presenting disseminated sporotrichosis with widespread cutaneous lesions mimicking pyoderma gangrenosum, with bone [...] Read more.
Sporotrichosis is a fungal disease that causes symptoms similar to those of other infectious and non-infectious diseases, making diagnosis difficult and challenging. Here, we report a case of an HIV-negative patient presenting disseminated sporotrichosis with widespread cutaneous lesions mimicking pyoderma gangrenosum, with bone marrow infection, pancytopenia, and hemophagocytic syndrome. However, all the clinical manifestations and a bacterial coinfection delayed the request for a fungal diagnosis. Therefore, sporotrichosis should always be investigated in patients from endemic areas presenting with widespread cutaneous lesions associated with pancytopenia. Full article
(This article belongs to the Special Issue Opportunistic Fungal Infections)
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