Table of Contents

Whole Allergen

m4 Mucor racemosus

m4 Mucor racemosus Scientific Information

Type:

Whole Allergen

Display Name:

Mucor racemosus

Allergen code:

Family:

Mucoraceae

Species:

Mucor racemosus

Route of Exposure:

Inhalation

Latin Name:

Mucor racemosus

WHO/ICD-11 code:

XN79P

(ICD-11 is currently under implementation by WHO and the ICD-11 codes displayed in the encyclopedia may not yet be available in all countries)

Summary

Mucor is a saprotrophic, ubiquitous microorganism found in the dung, plants or animal dead tissue/material, and employed as a food additive in some traditional cultures. Mucor genus has worldwide distribution. Mucor racemosus (M. racemosus) is an outdoor as well as an indoor mold. Its presence has been reported in homes, schools, hospitals, and water damaged buildings. M. racemosus thrives in environments with limited ventilation or sheltered from wind, high humidity, and poor light. Mucor species is characterized by columellate multi-spored sporangia. Inhalation of fungal spores is the primary route of exposure to the allergens, while ingestion of Mucor contaminated food may be the secondary route of exposure. M. racemosus induces mostly respiratory allergic reactions, such as asthma, allergic rhinitis, and sinusitis. Moreover, oral allergy symptoms and occasional anaphylaxis are reported. Occupational exposure to Mucor species may result in hypersensitivity pneumonitis and asthma among workers. The allergens of Mucor species have not yet been characterized. However, a detailed investigation of the cross-reactivity of Mucor with other mold species showed the presence of multiple common bands. Mucor hiemalis, a species related to M. racemosus, contains multiple IgE-binding proteins likely involved in cross-reactivity, but direct studies are lacking.

Allergen

Nature

Mucor is a huge fungal genus belonging to the order Mucorales currently consisting of more than 100 Mucor species (Mucor spp.). Mucor spp. are usually saprotrophs. They are ubiquitous microorganisms and frequently colonize various environments ranging from dungs and plant litters to plant and animal tissues. Some of the Mucor spp., such as M. indicus, M. ramosissimus, and some members of the M. circinelloides complex, but not M. racemosus, are thermotolerant (1), meaning they can grow at 37°C or above and cause fungal infection and mucormycosis. (1, 2).

M. racemosus is a facultatively anaerobic zygote fungi existing in both forms, mold and yeast. It grows either as a filamentous fungi or spherical yeasts in a vegetative manner (3). Under negative nutritional or environmental conditions, arthrospores are formed through septation of coenocytic hyphae and hyphal fragmentation. Growth and sporulation occur at 5-30^o Celsius with ideal growth and sporulation taking place at 20 to 25^o Celsius; no growth is reported at or above 37^o Celsius (2). It can grow at pH between 4 and 8 and has a water activity limit of 0.92 to 0.93. Mucor spp. needs fermentable hexose for growth. Further, the amount of hexose, partial pressure of CO_2, and source of nitrogen decide the existence in two different forms (dimorphism) in some of the Mucor spp. (2).

Several Mucor species show dimorphism, including M. racemosus, M. rouxi, M. bacilliformis, M. genevensis, and M. subtilissimus. They grow in the form of spherical multi-polar budding yeasts depending on certain environmental conditions (2)

Taxonomy

Mucor genus belongs to the order Mucorales (a phylogenetically ancient group of fungus) and phylum Zygomycota (1). This phylum consists of about 1000 species and the largest and most well-studied subphylum is Mucormycotina (3). The members of the phylum Zygomycota are characterized by sporangiospores (formed by asexual reproduction) that are air-borne. (1). The morphology of the sporangiospores, sporangia, columella, and sporangiophores are the distinguishing features among the members of order Mucorales (2).

*Taxonomic tree of M. racemosus* (3, 4)**
Domain	Eukaryota
Kingdom	Fungi
Phylum	Zygomycota
Subphylum	Mucoromycotina
Class	Mucormycetes
Order	Mucorales
Family	Mucoraceae
Genus	Mucor
Species	M. racemosus

Tissue

Mucor spp. is characterized by columellate multi-spored sporangia with small rhizoids and stolons (2).

M. racemosus sporangia color ranges from gray to a brown, diameter up to 80 µm or even sometimes 90 µm. Sporangiophores have sympodial and monopodial branching with a diameter of up to 18 µm. They are 10 µm long, 7 µm wide with about 8 µm diameter and are either elliptical or sub-globose in shape. The central part of the spore producing body (columellae) are either oval, elliptical, cylindrical, sub-spherical or pyriform in shape. Chlamydospores are frequently found in cultures with colony height up to 45 mm (2).

Epidemiology

Worldwide distribution

Mucor sensitization was an early finding in European allergic asthmatic patients, albeit with differences in prevalence across various regions and as a function of the diagnostic material employed, with figures varying from 3 to 40% (4).

In a cross-sectional study in Egypt, 19.4% of 62 (n=12) allergic bronchial asthma and allergic rhinitis (AR) patients showed a positive skin prick test (SPT) to M. racemosus allergen (5).

A Chinese study of adult and pediatric asthmatic patients with IgE sensitization to Aspergillus fumigatus (n = 54) or allergic broncho-pulmonary aspergillosis (n = 18) showed frequent co-sensitization to other molds, including M. racemosus in 25% and 50% of these patients respectively (6).

The prevalence of IgE sensitization to Mucor spp. may be significant as early as preschool age. Indeed, a 12-year survey in Mexico City found a prevalence of 10.3% and 11.8% respectively of M. mucedo positive SPT among 7565 mold-sensitized children. Of note, among the 8794 children aged 2-18, addressed for asthma, AR, or atopic dermatitis (AD), and receiving SPT investigation, 86% demonstrated SPT sensitization to at least one mold, with A. fumigatus (17%) being the most prevalent (7).

The relative contribution of genuine co-sensitization and cross-reactivity was not addressed in these studies, leaving open the question of the pathophysiological role of Mucor spp. in allergic diseases.

Environmental Characteristics

Living environment

M. racemosus was identified about 140 years ago from soil samples. It is an outdoor as well as indoor mold, found in dust samples (8).

They can also grow on contaminated foods or decaying plants and animals. They prefer to grow more in an environment with limited ventilation, high humidity, poor light, and without wind, mostly found in kitchens, bathrooms, laundry rooms, and basements. The allergens of such indoor fungi are present in the air in all seasons (8, 9)

Mucor genus is ubiquitous in nature and can be isolated from different sources, such as processed and unprocessed foods (2), cockroaches (10), or the esparto fibers traditionally used by Spanish and North-African craftsmen (11).

Mucor spp. was found with a prevalence of 5.5% in a Turkish study conducted on 91 mold isolates obtained from 69 traditional cheese samples [18 kasar cheese, 22 civil cheese, 23 lor (whey curd), 6 tulum cheese] (12).

Worldwide distribution

Mucor spp. are found worldwide in outdoor and indoor air, e.g. of homes, schools, hospitals, and water damaged buildings (3, 13, 14). In the Northern part of Norway, Mucor was found inside homes and schools during winter. Mucor was reported to be found commonly in Istanbul (isolated from air samples) and rarely in the Netherlands. In Asia, Mucor species is commercially used in the biotechnology industry for the production of food and beverages (4).

Route of Exposure

Main

The primary route of exposure to Mucor spp. allergen is the inhalation of fungal spores (9).

Secondary

Another route of exposure is oral i.e. ingestion of Mucor contaminated food (4). Penetration of the fungus, belonging to the order Mucorales, across damaged epithelium or a wound (surgical site, trauma) is also reported (15).

Clinical Relevance

Allergic rhinitis (AR) and and rhinosinusitis

M. racemosus may induce immunoglobulin E (IgE)-mediated sensitization and allergic reactions in asthmatic, allergic sinusitis, and AR patients (3, 16). Exposure and sensitization to Mucor spp. may lead to AR or worsen the condition (17). Mucor was found to be a common fungal genus associated with AR (18).

A study in Egypt found 6.4% of 94 patients with AR showing positive SPT to M. racemosus (5).

Hypersensitivity to mold is involved in chronic rhinosinusitis, with Mucor hypersensitivity known to cause allergic fungal rhinosinusitis. Lin et al. (2005) presented a case of 39-year-old Chinese male patient having a 10-year history of nasal congestion, a foul smell and occasional yellowish discharge. Histopathology showed fungal elements. Extensive investigation of fungal-induced sensitization evidenced high-level of monosensitization to M. racemosus, with no IgE binding to other mold species. The final diagnosis was Mucor induced sinus mycetoma in relation to immediate hypersensitivity to Mucor (19).

The association of fungi with the occurrence of nasal polyposis was studied in 190 patients with polyposis compared to 190 healthy individuals without chronic rhinosinusitis or nasal polyposis. M. racemosus positive SPT were found in 5.8% patients and 0.5% control individuals. IgE to M. racemosus was found in 1.8% of 170 patients but in no controls. Further, polyp samples from 138 patients and nasal secretions of 30 controls were cultured. Mucorales was found to be one of the common fungal species (9.8%) in the nasal cultures of 81 fungal positive patients; however, not detected in 18 positive controls (18).

Asthma

M. racemosus has been reported to induce sensitization in some individuals, as shown by skin-prick and provocation tests. It can also trigger allergen-induced exacerbation of asthma and rhinitis (3, 16).

A study in Egypt found 7.5% of 80 patients with allergic bronchial asthma showing positive SPT to M. racemosus (5).

Mucor species contaminated esparto grass (Poaceae family) fibers found in the Mediterranean region may induce occupational asthma or hypersensitivity pneumonitis in exposed workers. A case of a 30-year old man developing occupational asthma on exposure to esparto fibers contaminated with Mucor species had been reported, confirmed by positive Mucor SPT, detectable specific serum IgE against M. racemosus and a positive challenge test (4, 11)

Oral allergy symptoms and Anaphylaxis

In Central and Southern Europe, flavor-enhancing molds are commonly added to traditional foods such as dry sausage, salami, Spanish ham, and French cheese. A case was reported of a 24-year-old man diagnosed with rhino-conjunctivitis and asthma due to allergy to pollen, mites, and mold. He had experienced 2 episodes of facial angioedema immediately after eating a few slices of dry sausage, which he had tolerated previously on many occasions. SPTs were positive for grass pollen, house dust mites, and molds (such as Alternaria alternata, Penicillium chrysogenum, M. racemosus, and Pullularia, Stemphylium, Helminthosporum, and Fusarium spp.), and negative for all the food allergens tested. Specific (s)IgE was positive for Alternaria alternata (58 kU/L), M. racemosus (2.67 kU/L), and Penicillium chrysogenum (3.03 kU/L). Penicillium and Mucor spp. were isolated from the sausage skin. The labial challenge test yielded a positive result, with the onset of angioedema of the lips, tongue, and uvula within 5 minutes. The diagnosis was facial angioedema after dry sausage ingestion due to IgE-mediated food allergy to Penicillium and Mucor spp. The patient was advised to avoid all products commonly contaminated with molds, such as dry, fermented sausages, Spanish ham, foie gras, and French cheeses such as Roquefort and Camembert (20).

Bennett et al. (2001) reported a case of fatal anaphylaxis and death of a 19-year-old male (with a history of multiple allergies to pets, molds, and penicillin) on ingestion of mold-contaminated pancake. He did not develop any cutaneous symptoms, but experienced bronchospasm immediately after eating several pancakes and died within an hour. Autopsy showed laryngeal edema, hyperinflated lungs, mucous plugging, and chronic asthma. The pancake mix was found to be contaminated with Mucor, Penicillium, Aspergillus, and Fusarium molds, which were considered as the probable cause of anaphylaxis. (21).

Other diseases

Hypersensitivity pneumonia

There are several reports of hypersensitivity pneumonia due to M. racemosus. In a 44-year-old male cork worker, suberosis due to Mucor spp. was reported. The patient complained of bronchial obstruction, which is a rare presentation of hypersensitivity pneumonitis (22). Also, a study in Shanghai showed 20 cases of hypersensitivity pneumonitis among school teachers who were exposed to sugarcane contaminated with Mucor (4).

Sensitive skin syndrome

A study by Keum et al. (2020) evaluated microbiome and mycobiome of sensitive skin syndrome (SS) in 42 Korean women of age 22-52 years. The study found that M. racemosus was the most abundant fungus in SS patients, and suggested a link between M. racemosus and skin sensitivity (16).

Mucor spp. infections

Thermotolerant Mucor spp., which do not include M. racemosus, can cause local and invasive infections, especially in immunocompromised hosts. Mucor spp., together with Aspergillus spp., are prominent causes of invasive fungal rhinosinusitis in such patients (4). Mucormycosis is an emerging invasive fungal infection caused by the members of Mucorales in immunosuppressed individuals (23). It is the 3^rd most common fungal infection that can invade blood vessels and result in death (1). Mucormycosis has diverse clinical manifestations; the most prominent features include infections in rhino-orbito-cerebral, pulmonary, cutaneous, disseminated and gastrointestinal regions (24). Its incidence is increasing (23).

Molecular Aspects

Allergenic molecules

Mucor species allergens have not yet been characterized till date (4, 8, 25).

Cross-reactivity

Recent studies on Mucor cross-reactivity are scarce. Unsurprisingly, a detailed investigation of the cross-reactivity of Mucor with other mold species showed the presence of multiple bands (26). Some of these bands were later identified and characterized as fungal allergens in Fusarium spp., with potentially broad cross-reactivity among fungi including Mucor (26, 27). Among Mucor spp., Mucor hiemalis, a species related to M. racemosus, containing multiple IgE-binding proteins is likely to be involved in cross-reactivity, but direct studies are lacking (26).

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Christian Fischer

Last reviewed: February 2021

References

Lebreton A, Corre E, Jany J-L, Brillet-Guéguen L, Pérez Arques C, Garre V, et al. Comparative genomics applied to Mucor species with different lifestyles. BMC Genomics. 2019;21.
Botha A, Botes A. Mucor. Encyclopedia of Food Microbiology2014. p. 834-40.
Levetin E, Horner WE, Scott JA, Environmental Allergens W. Taxonomy of Allergenic Fungi. J Allergy Clin Immunol Pract. 2016;4(3):375-85 e1.
Weber RW. Allergen of the month--mucor. Ann Allergy Asthma Immunol. 2015;115(2):A15.
Elamawy M, Khatab N, Ibrahim A, Refaat M, Farres M, Ali A. Prevalence of sensitization to mould and yeast allergens in Egyptian patients with respiratory allergy. Benha Medical Journal. 2017;34(2).
Luo W, Hu H, Wu Z, Wei N, Huang H, Zheng P, et al. Molecular allergen sensitization of Aspergillus fumigatus between allergic bronchopulmonary aspergillosis and A fumigatus-sensitized asthma in Guangzhou, Southern China. J Clin Lab Anal. 2020;34(10):e23448.
Fernandez-Soto R, Navarrete-Rodriguez EM, Del-Rio-Navarro BE, Sienra-Monge JJL, Meneses-Sanchez NA, Saucedo-Ramirez OJ. Fungal Allergy: Pattern of sensitization over the past 11 years. Allergol Immunopathol (Madr). 2018;46(6):557-64.
Chang C, Leung PSC, Todi S, Zadoorian L. Definition of Allergens: Inhalants, Food, and Insects Allergens. Allergy and Asthma2019. p. 1-58.
Zukiewicz-Sobczak WA. The role of fungi in allergic diseases. Postepy Dermatol Alergol. 2013;30(1):42-5.
Yoder JA, Glenn BD, Benoit JB, Zettler LW. The giant Madagascar hissing-cockroach (Gromphadorhina portentosa) as a source of antagonistic moulds: concerns arising from its use in a public setting. Mycoses. 2008;51(2):95-8.
Enríquez A, Fernández C, Jiménez A, Seoane E, Alcorta AR, Rodríguez J. Occupational asthma induced by Mucor species contaminating esparto fibers. J Investig Allergol Clin Immunol. 2011;21(3):251-2.
Erdoğan A, Gurses M, Turkoglu H, S.Sert. The Determination of Mould Flora of Some Turkish Cheese Types (Kasar, Civil, Lor, Tulum). Pakistan Journal of Biological Sciences. 2001.
Odebode A, Adekunle A, Stajich J, Adeonipekun P. Airborne fungi spores distribution in various locations in Lagos, Nigeria. Environ Monit Assess. 2020;192(2):87.
Reddy MK, Srinivas T. Mold Allergens in Indoor Play School Environment. Energy Procedia. 2017;109:27-33.
Walther G, Wagner L, Kurzai O. Outbreaks of Mucorales and the Species Involved. Mycopathologia. 2020;185(5):765-81.
Keum HL, Kim H, Kim HJ, Park T, Kim S, An S, et al. Structures of the Skin Microbiome and Mycobiome Depending on Skin Sensitivity. Microorganisms. 2020;8(7).
Kołodziejczyk K, Bozek A. Clinical Distinctness of Allergic Rhinitis in Patients with Allergy to Molds. Biomed Res Int. 2016;2016:3171594-.
Muñoz-Del-Castillo F, Jurado-Ramos A, Soler R, Fernández-Conde BL, Barasona MJ, Cantillo E, et al. Fungal sensitization in nasal polyposis. J Investig Allergol Clin Immunol. 2009;19(1):6-12.
Lin R, Aziz MS, Yoo-Bowne H. Maxillary Sinus Mycetoma Associated With Hypersensitivity To Mucor Racemosus. The Internet Journal of Dermatology. 2005;5.
Bobolea I, Barranco P, Jurado-Palomo J, Pedrosa M, Quirce S. Allergy to Dry Fermented Sausage. Journal of investigational allergology & clinical immunology : official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología. 2009;19:324-5.
Bennett AT, Collins KA. An unusual case of anaphylaxis. Mold in pancake mix. Am J Forensic Med Pathol. 2001;22(3):292-5.
Villar A, Muñoz X, Cruz M-J, Morell F. Hypersensitivity Pneumonitis Caused by Mucor Species in a Cork Worker. Archivos de bronconeumología. 2009;45:405-7.
Binder U, Maurer E, Lass-Flörl C. Mucormycosis--from the pathogens to the disease. Clin Microbiol Infect. 2014;20 Suppl 6:60-6.
Thornton CR, Wills OE. Immunodetection of fungal and oomycete pathogens: established and emerging threats to human health, animal welfare and global food security. Crit Rev Microbiol. 2015;41(1):27-51.
WHO/IUIS. Mucor racemosus- Allergen Nomenclature; Accessed on December 22, 2020. 2020.
Verma J, Sridhara S, Singh BP, Gangal SV. Studies on shared antigenic/allergenic components among fungi. Allergy. 1995;50(10):811-6.
Verma J, Singh BP, Sridhara S, Gaur SN, Arora N. Purification and characterization of a cross-reactive 45-kD major allergen of Fusarium solani. Int Arch Allergy Immunol. 2003;130(3):193-9.