UNDERSTANDING THE ROLE OF FUNGI IN THE LARGER ECOSYSTEM: ANTIMICROBIAL RESISTANCE OF FUNGAL PATHOGENS

Bramante S, Di Michele S, Conti F, Rosati M. Understanding the role of fungi in the larger ecosystem: antimicrobial resistance of fungal pathogens. International Journal of Infection. 2024;8(1):20-23.

S. Bramante¹, S. Di Michele², F. Conti¹ and M. Rosati^1*

¹ Department of Gynaecology and Obstetrics, Pescara Civil Hospital, Italy;
² Division of Gynaecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy.

*Correspondence to:
Maurizio Rosati
Department of Obstetrics and Gynecology
Spirito Santo Hospital,
Pescara, Italy.
e-mail: maurizio.rosati18@outlook.com

Received: 01 February, 2024 Accepted: 26 April, 2024

ISSN 1972-6945 [online] Copyright 2024 © by Biolife-publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

ABSTRACT

Fungal spores are responsible for both seasonal and perennial allergic symptoms. Due to an increase in the use of broad-spectrum antifungals, antimicrobial resistance, including antifungal resistance, is a major concern in medical microbiology. Candida auris is a yeast that survives very well in the environment, and is a newcomer to the pathogenic world. The identified gene sequence of C. auris has allowed for better understanding of its pathogenicity and resistance.  Despite the new treatments used in recent years, antifungal therapy is still limited, and therefore, the study, isolation, and resistance of fungi is very complex and requires more global attention to avoid future infections that are currently increasing.

KEYWORDS: Fungi, Candida, antimicrobial resistance, fungal pathogen, infection

INTRODUCTION

Fungi need moisture to grow and flower and stagnate when the soil dries up. When the fungi stop growing and become dry, the wind carries their spores to different areas, where the spores remain above the ground and can survive for years. In this way, fungi spread from warm to cold places. Research has shown that fungal spores can become airborne at any time in dirty environments, causing particular susceptibility in exposed populations (1). Dusty and humid environments may indicate the presence of spores in the air where they can persist like other atmospheric particulates (2).

Fungal infection can present with diverse symptoms that affect different parts of the body and range in severity (Table I). Individuals affected by fungi are often unaware of the tests for detection, as there is a lack of awareness about the diseases that the spores can cause, and the symptoms can be confused with other infections, as often happens in the diagnosis of respiratory diseases such as pneumonia (3).

Table I. Possible complications from fungal infection.

Patients often resort to antibiotics, which is not useful or necessary because these drugs are utilized for bacterial infections and not for fungi (4). In these situations, the use of antibiotics can often favor the growth of fungi (5).

The peak of spore circulation occurs around mid-summer and then decreases in the winter period with the first frost. Spores are also transported by dry air that peaks in the early afternoon in conditions of low humidity, circulating Alternaria, Cladosporium, and Epinococcum species. The spores transported by humid air peak in the early hours of dawn when there is a high percentage of humidity, and these include ascospores, the sexual spores of Ascomycetes, and basidium spools (6).

Alternaria is the most common genus of fungi in places with dry and hot climates (7). It is commonly found in soil or on seeds and plants. This fungus produces a type of mold that is prevalent in southern Europe, which grows on decaying fruit and vegetables in particularly humid environments characterized by a temperature that varies between 18 and 32 degrees Celsius and a humidity rate greater than 65%. Alternaria commonly releases its spores on walls, carpets, and soil. Several studies have shown associations between Alternaria and severe asthma, conjunctivitis, rhinitis, and dermatitis (8). Sensitivity to Alternaria is considered a risk factor for severe asthma attacks and asthmatic epidemics (9).

Cladosporium is the most widespread spore in temperate regions and is the most commonly found fungus in outdoor environments where it is found on dead plants or vegetal substances (10).

Aspergillus is a genus that includes about 200 molds that is often isolated from house dust but is also found in compost piles and dead vegetation (11). The species belonging to this genus are strongly aerobic and grow in almost all oxygen-rich environments. Many species develop on starchy foods, especially if not vacuum-packed, such as cereals and potatoes. Several species also show the phenomenon of oligotrophy, meaning that they can grow in environments that are poor or even devoid of essential nutrients, such as Aspergillus niger, which can grow on damp walls (12). Aspergillus fumigatus and Aspergillus clavatus are the main species capable of causing allergies (13).

Penicillium is found in soil, food, cereals, and house dust. It grows in the water of old damaged buildings, on walls, and in decaying fabrics where it presents as a greenish color (14).

Exposure to allergens plays a significant role in the morbidity of asthma and can promote allergic sensitization in genetically susceptible individuals (15). It can therefore be confirmed that environmental factors play just as important a role as genetic factors in the development of asthma. An effective environmental allergen remediation must include a global approach that aims to prevent exposure to all allergens to which the subject is sensitized. A global prevention plan must also include a significant commitment from public health agencies (16). The current challenge is to find effective public health interventions capable of reducing the impact of atopic diseases.

People who spend a lot of time outside in dusty environments should be vaccinated against that particular fungus to stay uninfected (17). However, there are no vaccines available for any fungal disease to date. There are medications to treat fungi, but patients are often misdiagnosed (18). Fungal vaccines are currently being tested in many laboratories and have so far attracted much enthusiasm as they have produced a positive immune reaction in the body (19).

DISCUSSION

Continuous antimicrobic treatment of infections leads to an increase in antimicrobial resistance for both bacteria and fungi (20). The threat of antifungal resistance is a major global health concern. The World Health Organization (WHO) has published the first list of fungal “priority pathogens,” a catalogue of 19 fungi that pose a risk to public health, including Candida auris (21).

Resistance has been reported in both Candida species and Aspergillus and Trichophyton molds (22). This is due to an increase in the use of broad-spectrum antifungals, especially in hospitals and in environments where antifungals are frequently used, such as in agriculture. New diagnostic methods and treatment options for the emergence of resistant fungal pathogens (such as C. auris, Azole-resistant and Aspergillus species) should be studied more thoroughly (23).

C. auris is a yeast that survives very well in the environment and is a newcomer to the pathogenic world (C. auris is so named because it was first identified in 2009 in the ear of a Japanese woman). C. auris infection can be acquired in the hospital, is difficult to eradicate, and is also more resistant to disinfectants than other fungi. Due to their level of resistance, Candida species, including C. auris, require prompt treatment (24).

In recent years, the Centre for Disease Control (CDC) has reported that there has been a significant increase in fungal resistance to Candida species that has caused thousands of deaths in the United States (25). C. auris cases have increased exponentially in the last two years.

Fungi isolated from non-sterile bodies are often non-pathogenic. Yeasts are part of the human microbiome and their presence in the body is considered normal, especially in the gastrointestinal and genitourinary tracts. Yeasts can also be found in the upper respiratory tract but are rarely associated with influenza. Molds are not associated with the human microbiota; however, they are ubiquitous in nature and may play a pathological role (26).

Fungal spores can be isolated from affected respiratory tracts and grown in cultures for further study (27). They can be grown on agar plates during or before incubation, where antifungal-resistant can also be tested. Most laboratories are able to identify most yeasts. However, C. auris is difficult to routinely identify in many clinical tests (28). In fact, morphological and biochemical tests alone are not able to identify C. auris. Molecular and mass spectroscopy tests are the only reliable ones. The entire gene sequence identified has allowed to evaluate the photogenetic of the isolated material causing the infections. Invasive infections of Candida species are often associated with antifungal resistance; this is very important (29).

Some molecular microarray panels have been approved by the FDA and are used in many laboratories. These can rapidly and accurately detect commonly resistant yeast such as C. glabrata, C. krusei and most importantly, C. auris (30). However, with these microarray panels, no resistant markers were found. Pathogen identification is important because it allows for targeted antifungal therapy. Some kits allow the processing of blood cultures to create pellets of microorganisms that can be analyzed and identified rapidly. The accuracy of the methods used depends on the quality of the protein extracted and the instrument utilized. Note that these tests can identify Candida species associated with resistance, but they cannot detect resistance genes or provide data regarding antimicrobial susceptibility (31).

C. auris normally colonizes the skin and mucocutaneous tissue and swab analysis is done from the axilla and inguinal region. Often, patients with C. auris are asymptomatic if the skin infection is superficial, but they are predisposed to a more invasive infectious disease (32).

There are several types of screening, but the molecular test is very accurate and fast, and therefore, saves time. There are also other tests available that can identify not only C. auris, but also other potentially antimicrobial-resistant organisms including other Candida species. Mold diagnostic laboratories still rely on morphological characteristics. This process can take several weeks, depending on the growth characteristics of the organism being tested. Some tests for filamentous mold can shorten the identification time and often provide more informative details, such as species level determination, than morphological characteristics alone (33).

Mold diagnoses are non-invasive, as the spores of these organisms often do not infect blood (Fusarium species are an exception). In the case of Fusarium infection, diagnosis is made by collecting cultures of blood samples, but these have a low yield of detecting the invasive infectious fungus. The presence of specific fungal antigens in blood and body fluids may be useful in certain clinical cases. In the last 5 years, there has been an increase in genomic studies to identify invasive mold infections in high-risk patients, but specificity, cost and time limit the development of metagenomics (34).

The detection of resistance in mold isolates is often determined by the susceptibility of invasive tests or by the recruitment of treated resistant infections. The use of polymerase chain reaction (PCR) on formalin-fixed, paraffin-embedded tissues may be useful for rapid identification of invasive mold infections. Common resistance mechanisms can be identified with PCR (35).

C. auris is a multidrug-resistant isolate that has been identified globally. This strain is difficult to treat because it is resistant to various classes of anti-fungal therapy (36). Some of these strains also show resistance to anti-metabolite classes. There are 4 classes of C. auris, each possessing a different resistance (37).

For example, Azole resistance seems to be associated with the ERG11 and CDR1 genetic mutation (38). The ERG11 mutation is a member of the cytochrome P450 family and causes structural alterations and a decrease in the binding affinity of the enzyme with Azole (39). However, there are other mutations associated with Azole resistance. In the last 10 years, several novel anti-fungal agents have been discovered for the treatment of highly resistant fungi, but in many cases, the treatment is still limited.

CONCLUSIONS

The increase in antimicrobial resistance of fungal pathogens, including C. auris, is a global concern. Rapid and accurate identification of fungi is essential for the therapy of infections. The use of molecular methods for identification has replaced the now obsolete morphological method which is slow and less accurate. The new anti-fungal agents can provide more specific treatments for current and future invasive infections caused by highly resistant mold and yeast.

Conflict of interest

The authors declare that they have no conflict of interest.

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