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Scedosporium species rank second among the filamentous fungi colonizing the lungs of patients with cystic fibrosis (CF). Apart from the context of immunodeficiency (lung ...transplantation), the colonization of the CF airways by these fungi usually remains asymptomatic. Why the colonization of the lower airways by Scedosporium species is fairly tolerated by CF patients while these fungi are able to induce a marked inflammatory reaction in other clinical contexts remains questionable. In this regards, we were interested here in exploring the transcriptional reprogramming that accompanies the adaptation of these fungi to the particular microenvironment encountered in the airways of CF patients. Cultivation of Scedosporium apiospermum in conditions mimicking the microenvironment in the CF lungs was shown to induce marked transcriptional changes. This includes notably the down-regulation of enzymes involved in the synthesis of some major components of the plasma membrane which may reflect the ability of the fungus to evade the host immune response by lowering the biosynthesis of some major antigenic determinants or inhibiting their targeting to the cell surface through alterations of the membrane fluidity. In addition, this analysis revealed that some genes encoding enzymes involved in the biosynthesis of some mycotoxins were down-regulated suggesting that, during the colonization process, S. apiospermum reduces the production of some toxic secondary metabolites to prevent exacerbation of the immune system response. Finally, a strong up-regulation of many genes encoding enzymes involved in the degradation of aromatic compounds was observed, suggesting that these catabolic properties would predispose the fungus to particular patterns of human pathogenicity. Together these data provide new insights into the adaptative mechanisms developed by S. apiospermum in the CF lungs, which should be considered for identification of potential targets for drug development, but also for the experimental conditions to be used in in vitro susceptibility testing of clinical isolates to current antifungals.
L’exploration d’une hyperéosinophilie sanguine (HES) au retour de voyage est une démarche complexe qui requiert une collaboration étroite entre cliniciens et biologistes. La prise en charge du ...patient nécessite de rechercher dans un premier temps une cause fréquente (médicamenteuse, allergique ou parasitaire), mais aussi de s’assurer de l’absence d’effet délétère liée à l’HES elle-même. Dans un second temps, pourront être évoquées des étiologies plus rares telles que maladies de systèmes, maladies immunitaires et pathologies tumorales. Même au retour d’un séjour en zone tropicale où le risque parasitaire apparaît plus élevé, cette attitude diagnostique devra être respectée afin de ne pas écarter trop rapidement une étiologie non parasitaire.
L’interrogatoire du patient devra préciser la symptomatologie (fièvre, diarrhées, prurit…), rechercher la prise de médicaments, préciser les antécédents allergiques et recueillir des arguments épidémiologiques (origine géographique, profession, mode de vie, voyages, etc.). Une numération-formule sanguine de contrôle sera prescrite dans tous les cas, afin de confirmer l’HES. L’étude de la cinétique de cette dernière est d’ailleurs un élément important dans l’orientation diagnostique. L’examen parasitologique des selles, associé à la technique de Baermann si le patient a séjourné en zone tropicale ou intertropicale, sera renouvelé en cas de négativité. Des sérologies parasitaires seront ensuite prescrites, ciblant notamment anguillulose et toxocarose, respectivement première cause d’HES chez le voyageur et première étiologie autochtone. En cas de négativité du bilan parasitaire, un traitement d’épreuve anti-helminthique est parfois proposé.
The investigation of eosinophilia in returning travellers is a complicated process requiring a close collaboration between clinician physicians and biologists. First, a common cause (iatrogenic, allergic or parasitic etiology) should be investigated, but the absence of deleterious effects related to the eosinophilia itself should also be considered. Secondly, significant non-infective conditions such as sytemic, immune or tumoral diseases, should be discussed. Indeed, a non-parasitic etiology should not be too quickly excluded, even when returning from a high parasitic endemic area.
Symptoms of the patient (fever, diarrhea, pruritus, etc.), as well as medications and history of allergy should be collected. Besides, epidemiological arguments (native country, occupation, lifestyle, travel, etc.) should be rigorously considered. Eosinophilia have to be confirmed on a complete blood count. Moreover, kinetic study of the eosinophils level is an important element of etiological diagnosis. Three stool examinations will be carried out, along with Baermann’s technique if the patient comes from the tropics. Serological tests will then be performed, first targeting strongyloidiasis and toxocarosis. Empirical treatment targeting helminths may be considered for patients with negative results.
Schistosome dipeptide of love Le Govic, Yohann; Boissier, Jérôme; Papon, Nicolas
Trends in parasitology,
July 2022, 2022-Jul, 2022-07-00, 20220701, 2022-07, Volume:
38, Issue:
7
Journal Article
Peer reviewed
Open access
The female schistosome's dependence on the male to reach sexual maturity has puzzled scientists for decades. Using various molecular techniques, Chen et al. dissect the synthesis pathway of the ...β-alanyl-tryptamine dipeptide (BATT), emitted by the male into its environment, which induces sexual maturation and egg-laying in the female.
Une folliculite extensive de la barbe Chabasse, Dominique; Pihet, Marc; Le Govic, Yohann
Revue francophone des laboratoires,
June 2018, 2018-06-00, Volume:
2018, Issue:
503
Journal Article
Abstract
S10.5 Fungal respiratory infections in Cystic Fibrosis, September 24, 2022, 10:30 AM - 12:00 PM
Secondary metabolism is a general term defining biosynthetic pathways that occur in plants, ...bacteria, and fungi and lead to the production of highly diversified molecular structures. Among the diverse functions that were attributed to these molecules, it is now obvious that they are predominantly involved in chemical warfare with competitors in their environments. In fungi, the two main classes of fungal secondary metabolites are polyketides (PKs) and nonribosomal peptides (NRPs). The biosynthesis of such bioactive molecules is performed by large multifunctional enzymes (NRP synthases, NRPS, and polyketide synthases, PKS) encoded by genes usually located within clusters. Conversely to Aspergillus fumigatus, only a few data are currently available for other pathogenic fungi. In this context, our research group is interested in delineating the role of secondary metabolism in Scedosporium apiospermum, a multi-resistant mold known to colonize chronically the airways of patients with cystic fibrosis (CF).
Taking advantage of the availability of the S. apiospermum genome sequence, we first conducted an in silico analysis aiming at exploring the PKs and NRPs battery of the fungus. A total of 9 genes encoding PKs, 9 encoding NRPs, and 5 encoding hybrid NRPs/PKs enzymes were identified. All 3 of the PKs gene clusters presented homologies with those involved in the biosynthesis of pseurotin A. transbergamotene, and ovalicin, or the tremorgenic toxin b-aflatrem while a fourth one is involved in the biosynthesis of melanin. Among the NRPs encoding genes, 6 exhibited sufficient similarity scores with other fungal NRPs to predict the class of the generated peptide: siderophores (2), epidithiodioxopiperazines (2), and cyclopeptides (2). Nevertheless, substrate prediction methods for NRPs domains failed, thus questioning about the nature of the produced peptides. We thus focused our attention on the characterization of some NRP and PK biosynthetic pathways. Since iron acquisition is known to be crucial for the survival of microorganisms as for the virulence of numerous pathogens, we first investigated clusters predicted to be responsible for the biosynthesis of siderophores in S. apiospermum. For instance, we disrupted the SAPIO_CDS2806 gene, an ortholog of sidD which drives the production of the extracellular hydroxamate-type siderophore fusarinin C in Aspergillus fumigatus. A comparison of culture supernatants from sidD mutants and their parent strain revealed that S. apiospermum secretes a unique extracellular siderophore, namely Nα-methylcoprogen B and that sidD gene was essential for the biosynthesis of this siderophore. sidD mutation resulted in the lack of growth under iron limiting conditions. Interestingly, pyoverdine supported the growth of the parent strain only, suggesting that Nα-methylcoprogen B is required for iron acquisition from this Pseudomonas aeruginosa siderophore. Finally, the deletion of sidD resulted in the loss of virulence in a murine model of scedosporiosis.
Altogether, our results demonstrate that S. apiospermum sidD gene drives the synthesis of a unique extracellular siderophore, namely Nα-methylcoprogen B, which is essential for fungal growth and virulence. Above all, we also provide unprecedented data suggesting that this fungal siderophore scavenges iron from pyoverdine, which might explain the antagonism between S. apiospermum and P. aeruginosa in CF.
Description Un jeune garçon de 15 ans est hospitalisé pour malaise et perte de connaissance à la suite d'une dispute avec sa famille d'accueil temporaire. Le bilan étiologique complet, comprenant ...notamment un scanner cérébral injecté et un électroencéphalogramme, est sans particularité. Au cours de l'hospitalisation, on découvre une hématurie macroscopique, associée à des douleurs scrotales. Le reste de l'examen clinique est normal. Le patient est, par ailleurs, apyrétique et en parfait état général. À l'interrogatoire, on apprend qu'il est originaire de Côte d'Ivoire, qu'il vit le reste de l'année dans un foyer pour mineurs en Seine-Saint-Denis (93), et que son dernier séjour dans son pays natal remonte à cinq ans. Le bilan sanguin montre une légère hyperéosinophilie (1,1 G/L ; N inférieur à 0,5 G/L) sans aucune autre anomalie. Un examen cytobactériologique des urines confirme l'hématurie, accompagnée d'une leucocyturie. La culture est négative. Une échographie vésicale est pratiquée, montrant un épaississement pseudo-polypoïde isoéchogène sur la paroi postérieure de la vessie. Un examen parasitologique des urines est alors réalisé. Outre la présence d'hématies, plusieurs éléments attirent l'attention du microscopiste (figures 1A et 1B). La barre représente 50 μm.
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