Academic Journal
Amphotericin B resistance in Lomentospora prolificans is associated with a soluble cell wall component.
| Τίτλος: | Amphotericin B resistance in Lomentospora prolificans is associated with a soluble cell wall component. |
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| Συγγραφείς: | Grossman NT; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA., Casadevall A; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.; Divison of Infectious Diseases of the Johns Hopkins School of Medicine, Baltimore, Maryland, USA. |
| Πηγή: | Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2026 Oct 07; Vol. 70 (10), pp. e0091526. Date of Electronic Publication: 2026 Sep 16. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, American Society for Microbiology |
| Ιατρικοί όροι (MeSH): | Amphotericin B*/pharmacology , Antifungal Agents*/pharmacology , Cell Wall*/chemistry , Cell Wall*/drug effects , Cell Wall*/metabolism , Drug Resistance, Fungal*, Aspergillus fumigatus/drug effects ; Protoplasts/drug effects ; Hyphae/drug effects ; Spores, Fungal/drug effects ; Microbial Sensitivity Tests |
| Περίληψη: | Lomentospora prolificans is a pathogenic filamentous fungus that causes disease primarily in people with severely compromised immune systems. It is pan-resistant to antifungal drugs, but the mechanism of its resistance to amphotericin B (AMB) is unknown. In this study, our goal was to investigate the mechanism of resistance to AMB of L. prolificans. The AMB susceptibility of L. prolificans protoplasts were measured using broth microdilution. L. prolificans, either intact, homogenized, or fractionated, was incubated with AMB in broth. The same activity was carried out with Aspergillus fumigatus as a control. These broths were then used to prepare microdilution plates with Saccharomyces cerevisiae to determine the activity of the conditioned AMB. AMB was 16-fold more effective at inhibiting the growth of L. prolificans protoplasts than conidia, but only 2-fold more effective against A. fumigatus protoplasts than conidia. Incubation of L. prolificans hyphae with AMB in media diminished drug activity to a much greater extent than A. fumigatus, with an 8-fold greater fungal mass of the latter required to achieve the effect of the former. Homogenization and fractionation of L. prolificans revealed that the factor inhibiting AMB activity was soluble with a mass >100 kDa. DNase, trypsin, proteinase K, amyloglucosidase, SDS, and 0.22 μm filtration had no effect on the AMB resistance factor, while treatment with urea and acetonitrile inactivated it. In summary, we report a different mechanism for AMB resistance for L. prolificans based on the existence of a substance residing in the cell wall that can eliminate the antifungal activity of AMB. |
| Competing Interests: | The authors declare no conflict of interest. |
| Σχόλια: | Update of: bioRxiv. 2026 Jun 25:2026.06.25.734450. doi: 10.64898/2026.06.25.734450.. (PMID: 42395419) |
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| Contributed Indexing: | Keywords: Lomentospora prolificans; amphotericin B; resistance |
| Substance Nomenclature: | 7XU7A7DROE (Amphotericin B) 0 (Antifungal Agents) |
| Entry Date(s): | Date Created: 20260916 Date Completed: 20261007 Latest Revision: 20261024 |
| Update Code: | 20261024 |
| PubMed Central ID: | PMC13688863 |
| DOI: | 10.1128/aac.00915-26 |
| PMID: | 42747443 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1098-6596 |
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| DOI: | 10.1128/aac.00915-26 |