Parietal composition of Lichtheimia corymbifera: Differences between spore and germ tube stages and host-pathogen interactions.

The molecular composition and structural organization of the cell wall of filamentous fungi underlie the ability of the host to identify them as pathogens. Although the organization of the fungal cell wall, composed of 90% polysaccharides, is similar from one fungus to another, small variations condition their ability to trigger pattern recognition receptors. Because the incidence of mucormycosis, an emerging life-threatening infection caused by the species of the order Mucorales is increasing worldwide, the precise composition of the cell wall of two strains of Lichtheimia corymbifera was investigated in the early growth stages of germination (spores and germ-tubes) using trimethylsilylation and confocal microscopy. This study also characterizes the response of THP-1 cells to Mucorales. The study identified the presence of uncommon monosaccharides (fucose, galactose, and glucuronic acid) whose respective proportions vary according to the germination stage, revealing early parietal reorganization. Immunofluorescence studies confirmed the exposure of ß-glucan on the surface of swollen spores and germ-tubes. Both spores and germ-tubes of L. corymbifera promoted an early and strong pro-inflammatory response, through TLR-2. Our results show the singularity of the cell wall of the order Mucorales, opening perspectives for the development of specific diagnostic biomarkers.

Lichtheimia corymbifera is a causative agent of mucormycosis, an emerging invasive fungal infection. Deciphering cell wall composition can lead to the identification of a polysaccharide epitope, which could be used as a biomarker, useful for the diagnosis of mucormycosis.

The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis.

Invasive mucormycosis (IM) is a life-threatening infection caused by the fungal order Mucorales, its diagnosis is often delayed, and mortality rates range from 40-80% due to its rapid progression. Individuals suffering from hematological malignancies, diabetes mellitus, organ transplantations, and most recently COVID-19 are particularly susceptible to infection by Mucorales. Given the increase in the occurrence of these diseases, mucormycosis has emerged as one of the most common fungal infections in the last years. However, little is known about the host immune response to Mucorales. Therefore, we characterized the interaction among L. corymbifera-one of the most common causative agents of IM-and human monocytes, which are specialized phagocytes that play an instrumental role in the modulation of the inflammatory response against several pathogenic fungi. This study covered four relevant aspects of the host-pathogen interaction: i) The recognition of L. corymbifera by human monocytes. ii) The intracellular fate of L. corymbifera. iii) The inflammatory response by human monocytes against the most common causative agents of mucormycosis. iv) The main activated Pattern-Recognition Receptors (PRRs) inflammatory signaling cascades in response to L. corymbifera. Here, we demonstrate that L. corymbifera exhibits resistance to intracellular killing over 24 hours, does not germinate, and inflicts minimal damage to the host cell. Nonetheless, viable fungal spores of L. corymbifera induced early production of the pro-inflammatory cytokine IL-1ß, and late release of TNF-α and IL-6 by human monocytes. Moreover, we revealed that IL-1ß production predominantly depends on Toll-like receptors (TLRs) priming, especially via TLR4, while TNF-α is secreted via C-type lectin receptors (CTLs), and IL-6 is produced by synergistic activation of TLRs and CTLs. All these signaling pathways lead to the activation of NF-kB, a transcription factor that not only regulates the inflammatory response but also the apoptotic fate of monocytes during infection with L. corymbifera. Collectively, our findings provide new insights into the host-pathogen interactions, which may serve for future therapies to enhance the host inflammatory response to L. corymbifera.

Structure prediction and function characterization of WC-2 proteins in Blakeslea trispora.

Blakeslea trispora is known for its potential to produce an excess of carotenoids in mixed cultures of strains of opposite sex. The biosynthesis of ß-carotene in B. trispora is activated not only by sex hormone trisporic acid but also by light, especially blue light. In fungi, the most intensively investigated blue-light reception proteins are WC-1 and WC-2, and the two proteins form a transcription factor complex which is called WCC by their PAS domains. Notably, multiple genes similar to wc-1 and wc-2 have been identified and characterized in Phycomyces, Mucor, and Rhizopus. Here we report that there are four members of wc-2-like gene family in B. trispora genome: Btwc-2a, Btwc-2b, Btwc-2c, and Btwc-2d. When the mycelia were exposed to blue light, their transcription levels are regulated differentially. Except for BtWC-2b, which only has a PAS domain, the other three proteins contain both a PAS domain and a ZnF domain. BtWC-2a interacts with either BtWC-1a or BtWC-1c to form different photoreceptor complexes in yeast two-hybrid assays, which is the unique situation not yet described in other fungi. In addition, the protein-protein docking analysis by the predicted 3D structures showed that the two complexes are structurally different. These results suggested that WC proteins of B. trispora are still involved in light regulation by forming WCC and the regulation mechanism of the photobiology appears to be more complex.

Comparative immunopathogenesis in a murine model of inhalative infection with the mucormycetes Lichtheimia corymbifera and Rhizopus arrhizus.

Pathogenic mucormycetes induce diseases with considerable morbidity and mortality in immunocompromised patients. Virulence data comparing different Mucorales species and various underlying risk factors are limited. We therefore compared the pathogenesis of inhalative infection by Rhizopus (R.) arrhizus and Lichtheimia (L.) corymbifera in murine models for predominant risk factors for onset of infection. Mice with diabetes or treated with cyclophosphamide or cortisone acetate were challenged via the intranasal route with an isolate of R. arrhizus or L. corymbifera, respectively. Clinical, immunological and inflammation parameters as well as efficacy of posaconazole prophylaxis were monitored over 14 days. Whereas immunocompetent mice showed no clinical symptoms after mucormycete infection, mice treated with either cyclophosphamide (CP) or cortisone acetate (CA) were highly susceptible. Animals infected with the isolate of R. arrhizus showed prolonged survival and lower mortality, compared to those exposed to the L. corymbifera isolate. This lower virulence of R. arrhizus was risk factor-dependent, since diabetic mice died only after infection with Rhizopus, whereas all Lichtheimia-infected diabetic animals survived. Under posaconazole prophylaxis, both mucormycetes were able to establish breakthrough infections in CA- and CP-treated mice, but the course of infection was significantly delayed. Detailed analysis revealed that susceptibility of CA- and CP-treated mice could not be mimicked by exclusive lack or downmodulation of neutrophils, platelets or complement, but can be supposed to be the consequence of a broad immunosuppressive effect induced by the drugs. Both Lichtheimia corymbifera and Rhizopus arrhizus induce invasive mycoses in immunocompromised hosts after inhalative infection. Key parameters such as virulence and immunopathogenesis vary strongly according to fungal species and underlying risk group. Selected neutropenia is no sufficient risk factor for onset of inhalative mucormycosis.

Gongronella sp. w5 elevates Coprinopsis cinerea laccase production by carbon source syntrophism and secondary metabolite induction.

When sucrose was used as the carbon source, the Basidiomycete Coprinopsis cinerea showed poor growth and low laccase activity in pure culture, but greatly enhanced the level of laccase activity (>1800 U/L) during coculture with the Mucoromycete Gongronella sp. w5. As a result, the mechanism of laccase overproduction in coculture was investigated by starting from clarifying the function of sucrose. Results demonstrated that Gongronella sp. w5 in the coculture system hydrolyzed sucrose to glucose and fructose by an intracellular invertase. Fructose rather than glucose was supplied by Gongronella sp. w5  as the readily available carbon source for C. cinerea, and contributed to an alteration of its growth behavior and a basal laccase secretion of 110.6 ± 3.3 U/L. On the other hand, separating Gongronella sp. w5 of C. cinerea by transfer into dialysis tubes yielded the same level of laccase activity as without separation, indicating that enhanced laccase production probably resulted from the metabolites in the fermentation broth. Further investigation showed that the ethyl acetate-extracted metabolites generated by Gongronella sp. w5 induced C. cinerea laccase production. One of the laccase-inducing compounds namely p-hydroxybenzoic acid (HBA) was purified and identified from the extract. When using HBA as the inducer and fructose as the carbon source in monoculture, C. cinerea observed similar high laccase activity to that in coculture, and zymograms revealed the same expression of laccase Lcc9 as the main and Lcc1 and Lcc5 as the minor enzymes. Overall, our experiments verified that Gongronella sp. w5 elevates Coprinopsis cinerea laccase production by carbon source syntrophism and secondary metabolite induction.

Synergistic effect of natural antifungal agents for postharvest diseases of blackberry fruits.

BACKGROUND: Blackberry postharvest diseases are caused by fungal pathogens, and treatment of fruits with edible, natural products could reduce the postharvest losses and contribute to food sustainability. Based on the hypothesis that inhibition of fungal pathogens will significantly extend the shelf-life of food products, the effects of natural antifungal agents on fungal pathogens were tested. RESULTS: Two pathogenic fungal isolates, Aspergillus japonicus and Gilbertella persicaria, from infected blackberry fruits were identified morphologically using scanning electron microscopy and confirmed by DNA sequence analysis. The inhibitory effects and synergistic action of natural antifungal agents against the two fungal isolates were investigated. The results obtained demonstrated that the natamycin, chitosan and ferulic acid exhibited significant antifungal activities against the tested strains based on the calculated minimum inhibitory concentration. The best antifungal activity was obtained using a combination of ferulic acid and natamycin, which generated a total synergistic effect on both tested strains with a fractional inhibitory concentration index of 0.281. Application of the selected agents on postharvest blackberry fruits reduced the rot ratio and weight loss and also increased fruit firmness. In addition, the shelf-life of fresh blackberry fruits was extended up to 12-15 days at 4 °C and 90 ± 5% relative humidity. CONCLUSION: The combined utilization of ferulic acid and natamycin showed synergistic antifungal activity against two pathogenic fungal isolates, and extended the shelf life of fresh blackberry fruits up to 12-15 days. © 2018 Society of Chemical Industry.

Occurrence and species distribution of pathogenic Mucorales in unselected soil samples from France.

Mucormycosis is a life-threatening invasive fungal disease that affects a variety of patient groups. Although Mucorales are mostly opportunistic pathogens originating from soil or decaying vegetation, there are currently few data on prevalence of this group of fungi in the environment. The aim of the present study was to assess the prevalence and diversity of species of Mucorales from soil samples collected in France. Two grams of soil were homogenized in sterile saline and plated on Sabouraud dextrose agar and RPMI agar supplemented with itraconazole or voriconazole. Both media contained chloramphenicol and gentamicin. The plates were incubated at 35 ± 2 °C and checked daily for fungal growth for a maximum of 7 d. Mucorales were subcultured for purity. Each isolate was identified phenotypically and molecular identification was performed by ITS sequencing. A total of 170 soil samples were analyzed. Forty-one isolates of Mucorales were retrieved from 38 culture-positive samples. Among the recovered isolates, 27 Rhizopus arrhizus, 11 Mucor circinelloides, one Lichtheimia corymbifera, one Rhizopus microsporus and one Cunninghamella bertholletiae were found. Positive soil samples came from cultivated fields but also from other types of soil such as flower beds. Mucorales were retrieved from samples obtained in different geographical regions of France. Voriconazole-containing medium improved the recovery of Mucorales compared with other media. The present study showed that pathogenic Mucorales are frequently recovered from soil samples in France. Species diversity should be further analyzed on a larger number of soil samples from different geographic areas in France and in other countries.

Gastrointestinal mucormycosis in a child with acute lymphoblastic leukemia: An uncommon but ominous complication.

Invasive fungal infections constitute a major cause of morbidity and mortality in children undergoing therapy for hematological malignancies. We report a 1-year-old boy who was receiving chemotherapy for acute lymphoblastic leukemia. His clinical course was complicated by a clinical syndrome consistent with neutropenic enterocolitis to which he succumbed. Histopathology of the surgically resected bowel revealed evidence of mucormycosis. Gastrointestinal mucormycosis is an unusual presentation which requires high degree of clinical suspicion and aggressive management.

The mucormycete-host interface.

Mucormycosis is a fungal infection with fulminant angioinvasion leading to high morbidity and mortality in susceptible individuals. The major predisposing conditions are uncontrolled diabetes, neutropenia, malignancies, receipt of a transplant and traumatic injury [1]. Over the past decade, mucormycosis has become an emerging fungal infection due to the increase in patient groups presenting with these pre-disposing conditions and our medical advances in diagnosing the infection [2-4]. Yet, we currently lack clinical interventions to treat mucormycosis effectively. This in turn is due to a lack of understanding of mucormycosis pathogenesis. Here, we discuss our current understanding of selected aspects of interactions at the mucormycete-host interface. We will highlight open questions that might guide future research directions for investigations into the pathogenesis of mucormycosis and potential innovative therapeutic approaches.

Mucorales spores induce a proinflammatory cytokine response in human mononuclear phagocytes and harbor no rodlet hydrophobins.

Mucormycoses are life-threatening infections in immunocompromised patients. This study characterizes the response of human mononuclear cells to different Mucorales and Ascomycota. PBMC, monocytes, and monocyte derived dendritic cells (moDCs) from healthy donors were stimulated with resting and germinated stages of Mucorales and Ascomycota. Cytokine response and expression of activation markers were studied. Both inactivated germ tubes and resting spores of Rhizopus arrhizus and other human pathogenic Mucorales species significantly stimulated mRNA synthesis and secretion of proinflammatory cytokines. Moreover, R. arrhizus spores induced the upregulation of co-stimulatory molecules on moDCs and a specific T-helper cell response. Removal of rodlet hydrophobins by hydrofluoric acid treatment of A. fumigatus conidia resulted in enhanced immunogenicity, whereas the cytokine response of PBMCs to dormant R. arrhizus spores was not influenced by hydrofluoric acid. Scanning electron micrographs of Mucorales spores did not exhibit any morphological correlates of rodlet hydrophobins. Taken together, this study revealed striking differences in the response of human mononuclear cells to resting stages of Ascomycota and Mucorales, which may be explained by absence of an immunoprotective hydrophobin layer in Mucorales spores.

Ketoacidosis alone does not predispose to mucormycosis by Lichtheimia in a murine pulmonary infection model.

Mucormycosis is a rare fungal infection; however, the number of cases increased during the last decades. The main risk factors are immunosuppression and uncontrolled diabetes mellitus. Although Lichtheimia species represent a common cause of mucormycosis in Europe, virulence and pathogenesis of this genus has not been investigated in detail yet. Using murine pulmonary infection models, we found that immunosuppression is essential for establishment of infection. The disease was characterized by necrosis, angioinvasion, thrombosis, and the lethal course of infection was associated with systemic activation of platelets. Furthermore, dissemination to internal organs was frequently observed. While the virulence potential of individual L. corymbifera and L. ramosa isolates differed, pathogenicity of both species was comparable. Although ketoacidosis promoted Rhizopus infection in mice, it did not predispose mice to infection with Lichtheimia in the absence of additional immunosuppression. This might partially explain the dominance of Rhizopus as cause of mucormycosis in countries with high prevalence of ketoacidotic patients.

Pathogenic nature of Syncephalastrum in Atta sexdens rubropilosa fungus gardens.

BACKGROUND: Leaf-cutter ants are considered to be a major herbivore and agricultural pest in the Neotropics. They are often controlled by environmentally persistent insecticides. Biological control using pathogenic fungi is regarded as an alternative for the management of these insects. Here, we assess whether the filamentous fungus Syncephalastrum sp. is a pathogenic microorganism responsible for a characteristic disease in fungus gardens. We also characterise the damage caused by this fungus by evaluating physiological and behavioural responses of Atta sexdens rubropilosa subcolonies infected with Syncephalastrum sp. RESULTS: Syncephalastrum sp. fulfils Koch's postulates characterising it as a pathogenic microorganism. Ant workers recognise the infection and remove contaminated fragments from the fungus garden. Syncephalastrum sp. infection causes an interruption of foraging activity, an increase in ant mortality, subcolony deterioration and an increase in the amount of waste generated, all resulting in subcolony death. Syncephalastrum sp. also inhibits the ant fungal cultivar in vitro. The pathogenic effect of Syncephalastrum sp. does not depend on host morbidity or stress (e.g. worker mortality caused by an entomopathogenic fungus). CONCLUSION: Syncephalastrum sp. treatment resulted in progressive damage in subcolonies. The interactions among Syncephalastrum sp., fungus garden and ants offer new opportunities in integrated pest management of leaf-cutter ants. © 2016 Society of Chemical Industry.

Stress response in medically important Mucorales.

Mucorales are saprobes, ubiquitously distributed and able to infect a heterogeneous population of human hosts. The fungi require robust stress responses to survive in human host. We tested the growth of Mucorales in the presence of different abiotic stress. Eight pathogenic species of Mucorales, including Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, Apophysomyces elegans, Licthemia corymbifera, Cunninghamella bertholletiae, Syncephalastrum racemosum and Mucor racemosus, were exposed to different stress inducers: osmotic (sodium chloride and d-sorbitol), oxidative (hydrogen peroxide and menadione), pH, cell wall and metal ions (Cu, Zn, Fe and Mg). Wide variation in stress responses was noted: R. arrhizus showed maximum resistance to both osmotic and oxidative stresses, whereas R. pusillus and M. indicus were relatively sensitive. Rhizopus arrhizus and R. microsporus showed maximum resistance to alkaline pH, whereas C. bertholletiae, L. corymbifera, M. racemosus and A. elegans were resistant to acidic pH. Maximum tolerance was noted in R. microsporus to Cu, R. microsporus and R. arrhizus to Fe and C. bertholletiae to Zn. In contrast, L. corymbifera, A. elegans and M. indicus were sensitive to Cu, Zn and Fe respectively. In conclusion, R. arrhizus showed high stress tolerance in comparison to other species of Mucorales, and this could be the possible reason for high pathogenic potential of this fungi.

Filamentous Fungi.

Filamentous mycoses are often associated with significant morbidity and mortality. Prompt diagnosis and aggressive treatment are essential for good clinical outcomes in immunocompromised patients. The host immune response plays an essential role in determining the course of exposure to potential fungal pathogens. Depending on the effectiveness of immune response and the burden of organism exposure, fungi can either be cleared or infection can occur and progress to a potentially fatal invasive disease. Nonspecific cellular immunity (i.e., neutrophils, natural killer [NK] cells, and macrophages) combined with T-cell responses are the main immunologic mechanisms of protection. The most common potential mold pathogens include certain hyaline hyphomycetes, endemic fungi, the Mucorales, and some dematiaceous fungi. Laboratory diagnostics aimed at detecting and differentiating these organisms are crucial to helping clinicians make informed decisions about treatment. The purpose of this chapter is to provide an overview of the medically important fungal pathogens, as well as to discuss the patient characteristics, antifungal-therapy considerations, and laboratory tests used in current clinical practice for the immunocompromised host.

The role of oxidative stress on carotene production by Blakeslea trispora in submerged fermentation.

In aerobic metabolism, reactive oxygen species (ROS) are formed during the fermentation that can cause oxidative stress in microorganisms. Microbial cells possess both enzymatic and non-enzymatic defensive systems that may protect cells from oxidative damage. The antioxidant enzymes superoxide dismutase and catalase are the two key defensive enzymes to oxidative stress. The factors that induce oxidative stress in microorganisms include butylated hydroxytoluene (BHT), hydrogen peroxide, metal ions, dissolved oxygen tension, elevated temperature, menadione, junglone, paraquat, liquid paraffin, introduction to bioreactors of shake flask inocula and synthetic medium sterilized at initial pH 11.0. Carotenes are highly unsaturated isoprene derivatives. They are used as antioxidants and as coloring agents for food products. In fungi, carotenes are derived via the mevalonate biosynthesis pathway. The key genes in carotene biosynthesis are hmgR, ipi, isoA, carG, carRA and carB. Among microorganisms, Βlakeslea trispora is the main microorganism used for the production of carotenes on the industrial scale. Currently, the synthetic medium is considered the superior substrate for the production of carotenes in a pilot plant scale. The fermentation systems used for the production of carotenes include shake flasks, stirred tank fermentor, bubble column reactor and flat panel photobioreactor. This review summarizes the oxidative stresses in microorganisms and it is focused on the current status of carotene production by B. trispora including oxidative stress induced by BHT, enhanced dissolved oxygen levels, iron ions, liquid paraffin and synthetic medium sterilized at an initial pH 11.0. The oxidative stress induced by the above factors increases significantly the production of carotenes. However, to further reduce the cost of carotene production, new biotechnological methods with higher productivity still need to be explored.

Bone and joint infections by Mucorales, Scedosporium, Fusarium and even rarer fungi.

Mucorales, Scedosporium and Fusarium species are rarely considered as cause for bone and joint infections. However, these moulds are emerging as important fungal pathogens in immunocompromised and immunocompetent patients. Typical pre-disposing host conditions are immunosuppression and diabetes. Most common causative pathogens are Mucorales followed by Scedosporium and Fusarium. Acremonium and Phialemonium species are rare but some case reports exist. MRI is the gold standard imaging technique. Tissue specimens obtained as aspirates, imaging guided biopsy or open surgery need mycological and histopathological work-up for genus and species identification. Multimodal treatment strategies combine surgical debridement, drainage of joints or abscesses, removal of infected prosthetic joints and systemic antifungals. The treatment of mucormycosis is polyene based and may be combined with either posaconazole or - in rare cases - caspofungin. As Scedosporium species are intrinsically resistant to polyenes and azoles show absence of in vitro activity, voriconazole plus synergistic treatment regimens become the therapeutic standard. In fusariosis, fungal susceptibility is virtually impossible to predict, so that combination treatment of voriconazole and lipid-based amphotericin B should be the first-line strategy while susceptibility results are pending. In the absence of randomized controlled trials, infections due to the above moulds should be registered, e.g. in the registries of the European Confederation of Medical Mycology (ECMM).

Cokeromyces recurvatus identified in lung biopsy: case report of a non-pathogenic fungus, highlighting its potential histologic mimics.

We report a case of aspiration in a patient with gastric outlet obstruction due to pancreatic adenocarcinoma, in which three large yeasts were identified on tissue biopsy of the lung infiltrate. The histologic sections of the yeasts showed densely eosinophilic, round to oval, thick-walled structures with frayed borders and intra-cystic bluish inclusions. There was a background of mixed neutrophilic and eosinophilic infiltrate along with focal tissue necrosis. Our initial differential diagnoses included the usual large yeasts such as Cryptococcus, Coccidioides, and Blastomyces. Immunohistochemistry revealed reactivity to the Blastomyces antibody. Mycology studies eventually identified the organism as Cokeromyces recurvatus. Anti-fungal treatment was withheld with spontaneous resolution of the infiltrates. This case demonstrates the importance of using culture to speciate organisms identified on tissue, separating pathogens from non-pathogens and non-living artifacts in order for appropriate management.

Abutilon theophrasti's defense against the allelochemical benzoxazolin-2(3H)-one: support by Actinomucor elegans.

Abutilon theophrasti Medik., previously found to be rather insensitive to benzoxazinoid containing rye mulch and the allelochemical benzoxazolin-2(3H)-one (BOA), can be associated with the zygomycete Actinomucor elegans, whereby the fungus colonizes the root relatively superficially and mainly in the maturation zone. The fungus mitigates necrosis of the cotyledons when seedlings are incubated with 2 mM BOA, in contrast to those that lack the fungus. In liquid cultures of the fungus, tryptophan was identified. The accumulation of tryptophan is increased in presence of BOA. This amino acid seems to be important in protecting Abutilon against BOA and its derivatives since it suppressed the accumulation of BOA derived, highly toxic 2-aminophen-oxazin-3-one (APO) in the medium and on the root surface during BOA incubations of Abutilon seedlings. Although A. elegans is insensitive to BOA and APO, the fungus is not able to protect the plant against harmful effects of APO, when seedlings are treated with the compound. Abutilon can detoxify BOA via BOA-6-OH glucosylation probably by a cell wall associated glucosyltransferase, but only low amounts of the product accumulate. Low tryptophan concentrations can contribute to a degradation of the toxic intermediate BOA-6-OH by Fenton reactions, whereby the amino acid is oxidized. One of the oxidation products was identified as 4(1H)-quinolinone, which is the core substructure of the quorum sensing molecule 2-heptyl-3-hydroxy-4-quinolone. The mutualistic association of Abutilon theophrasti with Actinomucor elegans is considered as opportunistic and facultative. Such plant-fungus associations depend rather likely on environmental conditions, such as the mode of fertilization.

Chronic rhinocerebral mucormycosis: a rare case report and review of the literature.

Rhinocerebral mucormycosis is an invasive infection caused by filamentous fungi of the Mucoraceae family. The rhinocerebral form of the disease represents the most common form and has two distinct clinical entities. The common presentation consists of a rapidly progressive infection with high mortality rate, while the other presentation is that of a chronic infection with lower mortality. In the present paper we report a rare case of chronic rhinocerebral mucormycosis. An 85-year-old male with a 6-month history of purulent and odorous nasal discharge, and sporadic episodes of epistaxis and anosmia, presented to the outpatient department of our clinic. Initial cultures were positive only for Pseudomonas aeruginosa. The patient was unresponsive to ciprofloxacin treatment, developing necrotic areas of the nasal septum suspicious for rhinocerebral mucormycosis. Admission to the ENT clinic followed, with histopathologic evaluation of the vomer bone confirming the diagnosis. The patient was treated with amphotericin B and was discharged 3 weeks later on oral posaconazole therapy. Chronic rhinocerebral mucormycosis may present with atypical symptoms or coinfection with another agent. A high degree of clinical suspicion is required for correct diagnosis and prompt initiation of appropriate treatment.