Mycopathologia最新文献

Candida auris is a pathogenic yeast frequently exhibiting multidrug resistance and thus warrants special attention. The prompt detection and proper identification of this organism are needed to prevent its spread in healthcare facilities. The authors of this paper had previously developed LAMPAuris, a loop-mediated isothermal amplification assay, for the specific detection of C. auris. LAMPAuris is evaluated in this report for its ability to identify C. auris from five clades and to detect it from clinical specimens. A total of 103 skin swab samples were tested in comparison with a culture-based method and C. auris-specific SYBR green qPCR. The results show that the LAMPAuris assay had specificities ranging from 97 to 100% and sensitivities ranging from 66 to 86%. The lower sensitivity could be attributed to DNA degradation caused by the prolonged storage of the samples. In conclusion, LAMPAuris proved to be a rapid and reliable method for identifying C. auris and for detecting it in clinical specimens. Fresh specimens should ensure better yield and higher sensitivities.

Caspofungin, a lipopeptide, is an antifungal drug that belong to the class of echinocandin. It inhibits fungal cell wall β-(1,3)-glucan synthase activity and is the second-line of drug for invasive aspergillosis, a fatal infection caused mainly by Aspergillus fumigatus. On the other hand, Enfumafungin is a natural triterpene glycoside also with a β-(1,3)-glucan synthase inhibitory activity and reported to have antifungal potential. In the present study, we compared the growth as well as modifications in the A. fumigatus cell wall upon treatment with Caspofungin or Enfumafungin, consequentially their immunomodulatory capacity on human dendritic cells. Caspofungin initially inhibited the growth of A. fumigatus, but the effect was lost over time. By contrast, Enfumafungin inhibited this fungal growth for the duration investigated. Both Caspofungin and Enfumafungin caused a decrease in the cell wall β-(1,3)-glucan content with a compensatory increase in the chitin, and to a minor extent they also affected cell wall galactose content. Treatment with these two antifungals did not result in the exposure of β-(1,3)-glucan on A. fumigatus mycelial surface. Enzymatic digestion suggested a modification of β-(1,3)-glucan structure, specifically its branching, upon Enfumafungin treatment. While there was no difference in the immunostimulatory capacity of antifungal treated A. fumigatus conidia, alkali soluble-fractions from Caspofungin treated mycelia weakly stimulated the dendritic cells, possibly due to an increased content of immunosuppressive polysaccharide galactosaminogalactan. Overall, we demonstrate a novel mechanism that Enfumafungin not only inhibits β-(1,3)-glucan synthase activity, but also causes modifications in the structure of β-(1,3)-glucan in the A. fumigatus cell wall.

Malassezia, the most abundant fungal commensal on the mammalian skin, has been linked to several inflammatory skin diseases such as atopic dermatitis, seborrheic dermatitis and psoriasis. This study reveals that epicutaneous application with Malassezia globosa (M. globosa) triggers skin inflammation in mice. RNA-sequencing of the resulting mouse lesions indicates activation of Interleukin-17 (IL-17) signaling and T helper 17 (Th17) cells differentiation pathways by M. globosa. Furthermore, our findings demonstrate a significant upregulation of IL-23, IL-23R, IL-17A, and IL-22 expressions, along with an increase in the proportion of Th17 and pathogenic Th17 cells in mouse skin exposed to M. globosa. In vitro experiments illustrate that M. globosa prompts human primary keratinocytes to secrete IL-23 via TLR2/MyD88/NF-κB signaling. This IL-23 secretion by keratinocytes is shown to be adequate for inducing the differentiation of pathogenic Th17 cells in the skin. Overall, these results underscore the significant role of Malassezia in exacerbating skin inflammation by stimulating IL-23 secretion by keratinocytes and promoting the differentiation of pathogenic Th17 cells.

Graphic Abstract

Background

Recent data support ¹⁸F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of ¹⁸F-FDG PET-CT in IFI, in order to define areas of uncertainty.

Methods

An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to ¹⁸F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed.

Results

180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to ¹⁸F-FDG PET-CT at their own center. 85.6% considered that ¹⁸F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing ¹⁸F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up ¹⁸F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which ¹⁸F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status.

Conclusion

Although the majority considered that ¹⁸F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.

Cystic fibrosis (CF) is a genetic disorder characterized by chronic microbial colonization and inflammation of the respiratory tract (RT), leading to pulmonary exacerbation (PEx) and lung damage. Although the lung bacterial microbiota has been extensively studied, the mycobiome remains understudied. However, its importance as a contributor to CF pathophysiology has been highlighted. The objective of this review is to provide an overview of the current state of knowledge regarding the mycobiome, as described through NGS-based studies, in patients with CF (pwCF).

Several studies have demonstrated that the mycobiome in CF lungs is a dynamic entity, exhibiting a lower diversity and abundance than the bacterial microbiome. Nevertheless, the progression of lung damage is associated with a decrease in fungal and bacterial diversity. The core mycobiome of the RT in pwCFs is mainly composed of yeasts (Candida spp., Malassezia spp.) and molds with lower abundance. Some fungi (Aspergillus, Scedosporium/Pseudallescheria) have been demonstrated to play a role in PEx, while the involvement of others (Candida, Pneumocystis) remains uncertain. The “climax attack” ecological model has been proposed to explain the complexity and interplay of microbial populations in the RT, leading to PEx and lung damage. NGS-based studies also enable the detection of intra- and interkingdom correlations between fungi and bacteria. Further studies are required to ascertain the biological and pathophysiological relevance of these correlations. Finally, with the recent advent of CFTR modulators, our understanding of the pulmonary microbiome and mycobiome in pwCFs is about to change.

Mycetoma can be caused either by fungi or aerobic Actinomycetes. A precise identification of the causal agents is critical for the therapeutic outcome. Thus, this study aimed to identify the pathogens of mycetoma using 16S/ITS rRNA gene polymerase chain reaction (PCR) followed by Sanger sequencing directly on grains. In sum, 32 samples including 15 black grains, 12 red grains, and five white/yellow grains collected from patients with mycetoma at the Aristide Le Dantec University Hospital in Dakar, Senegal, between October 2014 and September 2020 were submitted to PCR/sequencing. For black grain eumycetoma, the ITS rRNA region was targeted. Similarly, the 16S rRNA gene was targeted for red grain actinomycetoma. These two regions were targeted in parallel for white/yellow grains, which could be of either bacterial or fungal origin. The age of the patients ranged from 14 to 72 years with a mean age of 36 ± 14 years. Thirteen (86%) of the 15 samples with black grains, were successfully sequenced with only one established eumycetoma pathogen, Madurella mycetomatis identified in 11 (73%). Cladosporium sphaerospermum was identified in one sample. For the 16S rRNA sequencing of red grains, a 58.3% (7/12) success rate was obtained with Actinomadura pelletieri identified in six samples. Among the five samples sequenced twice, the 16S rRNA allowed us to identify the causative agent in 2 cases, A. madurae in one, and A. geliboluensis in the other. The ITS rRNA identified 3 fungi, of which none was a mycetoma agent. Overall, direct 16S/ITS rRNA sequencing of the grains for detecting and identifying mycetoma pathogens was successful in 59.4% of cases. Fungi, led by M. mycetomatis, were the predominant pathogens identified. Two probable new mycetoma agents, C. sphaerospermum, and A. geliboluensis were identified and both deserve to be confirmed in further studies.

We describe for the first time, a high-quality genome for a rare human yeast pathogen Candida mucifera, from a patient with chronic suppurative otitis media. This pathogen exhibited reduced azole susceptibility, similar to its close relatives within the Trichomonascus ciferrii species complex.