FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4283260025> ?p ?o ?g. }

• W4283260025 endingPage "e1010417" @default.
• W4283260025 startingPage "e1010417" @default.
• W4283260025 abstract "Intracellular pathogens secrete effectors to manipulate their host cells. Histoplasma capsulatum (Hc) is a fungal intracellular pathogen of humans that grows in a yeast form in the host. Hc yeasts are phagocytosed by macrophages, where fungal intracellular replication precedes macrophage lysis. The most abundant virulence factor secreted by Hc yeast cells is Calcium Binding Protein 1 (Cbp1), which is absolutely required for macrophage lysis. Here we take an evolutionary, structural, and cell biological approach to understand Cbp1 function. We find that Cbp1 is present only in the genomes of closely related dimorphic fungal species of the Ajellomycetaceae family that lead primarily intracellular lifestyles in their mammalian hosts (Histoplasma, Paracoccidioides, and Emergomyces), but not conserved in the extracellular fungal pathogen Blastomyces dermatitidis. We observe a high rate of fixation of non-synonymous substitutions in the Cbp1 coding sequences, indicating that Cbp1 is under positive selection. We determine the de novo structures of Hc H88 Cbp1 and the Paracoccidioides americana (Pb03) Cbp1, revealing a novel binocular fold consisting of a helical dimer arrangement wherein two helices from each monomer contribute to a four-helix bundle. In contrast to Pb03 Cbp1, we show that Emergomyces Cbp1 orthologs are unable to stimulate macrophage lysis when expressed in the Hc cbp1 mutant. Consistent with this result, we find that wild-type Emergomyces africanus yeast are able to grow within primary macrophages but are incapable of lysing them. Finally, we use subcellular fractionation of infected macrophages and indirect immunofluorescence to show that Cbp1 localizes to the macrophage cytosol during Hc infection, making this the first instance of a phagosomal human fungal pathogen directing an effector into the cytosol of the host cell. We additionally show that Cbp1 forms a complex with Yps-3, another known Hc virulence factor that accesses the cytosol. Taken together, these data imply that Cbp1 is a fungal virulence factor under positive selection that localizes to the cytosol to trigger host cell lysis." @default.
• W4283260025 created "2022-06-23" @default.
• W4283260025 creator A5006176014 @default.
• W4283260025 creator A5015702226 @default.
• W4283260025 creator A5044565299 @default.
• W4283260025 creator A5046473582 @default.
• W4283260025 creator A5048039251 @default.
• W4283260025 creator A5049808247 @default.
• W4283260025 creator A5052538353 @default.
• W4283260025 creator A5054769799 @default.
• W4283260025 creator A5085913218 @default.
• W4283260025 date "2022-06-22" @default.
• W4283260025 modified "2023-10-09" @default.
• W4283260025 title "Cbp1, a fungal virulence factor under positive selection, forms an effector complex that drives macrophage lysis" @default.
• W4283260025 cites W1498013989 @default.
• W4283260025 cites W1581820685 @default.
• W4283260025 cites W1597678601 @default.
• W4283260025 cites W1670380555 @default.
• W4283260025 cites W1676185363 @default.
• W4283260025 cites W1839870563 @default.
• W4283260025 cites W1933001808 @default.
• W4283260025 cites W1935355922 @default.
• W4283260025 cites W1939782984 @default.
• W4283260025 cites W1956380765 @default.
• W4283260025 cites W1983043901 @default.
• W4283260025 cites W1985001505 @default.
• W4283260025 cites W1990299806 @default.
• W4283260025 cites W1997579901 @default.
• W4283260025 cites W2000022447 @default.
• W4283260025 cites W2002264839 @default.
• W4283260025 cites W2003564377 @default.
• W4283260025 cites W2008157480 @default.
• W4283260025 cites W2016336737 @default.
• W4283260025 cites W2022131661 @default.
• W4283260025 cites W2023008751 @default.
• W4283260025 cites W2029582401 @default.
• W4283260025 cites W2047399603 @default.
• W4283260025 cites W2053352075 @default.
• W4283260025 cites W2065283382 @default.
• W4283260025 cites W2082818161 @default.
• W4283260025 cites W2091506983 @default.
• W4283260025 cites W2103475644 @default.
• W4283260025 cites W2104804511 @default.
• W4283260025 cites W2107794472 @default.
• W4283260025 cites W2110335151 @default.
• W4283260025 cites W2110909388 @default.
• W4283260025 cites W2111647009 @default.
• W4283260025 cites W2125404003 @default.
• W4283260025 cites W2127685293 @default.
• W4283260025 cites W2132811240 @default.
• W4283260025 cites W2133815101 @default.
• W4283260025 cites W2138122982 @default.
• W4283260025 cites W2138151051 @default.
• W4283260025 cites W2140872496 @default.
• W4283260025 cites W2141741740 @default.
• W4283260025 cites W2143751636 @default.
• W4283260025 cites W2145347922 @default.
• W4283260025 cites W2150499428 @default.
• W4283260025 cites W2153132589 @default.
• W4283260025 cites W2158714788 @default.
• W4283260025 cites W2160535316 @default.
• W4283260025 cites W2171468042 @default.
• W4283260025 cites W2274126414 @default.
• W4283260025 cites W2280525799 @default.
• W4283260025 cites W2280733329 @default.
• W4283260025 cites W2404703480 @default.
• W4283260025 cites W2537065834 @default.
• W4283260025 cites W2587328382 @default.
• W4283260025 cites W2626652551 @default.
• W4283260025 cites W2765196390 @default.
• W4283260025 cites W2784993029 @default.
• W4283260025 cites W2792754106 @default.
• W4283260025 cites W2803473238 @default.
• W4283260025 cites W2894938254 @default.
• W4283260025 cites W2950094403 @default.
• W4283260025 cites W2954283679 @default.
• W4283260025 cites W2973753224 @default.
• W4283260025 cites W2980170804 @default.
• W4283260025 cites W3095468096 @default.
• W4283260025 cites W3110933951 @default.
• W4283260025 cites W3129795073 @default.
• W4283260025 cites W3159175725 @default.
• W4283260025 cites W345286992 @default.
• W4283260025 cites W4211184388 @default.
• W4283260025 cites W4233590982 @default.
• W4283260025 doi "https://doi.org/10.1371/journal.ppat.1010417" @default.
• W4283260025 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35731824" @default.
• W4283260025 hasPublicationYear "2022" @default.
• W4283260025 type Work @default.
• W4283260025 citedByCount "3" @default.
• W4283260025 countsByYear W42832600252022 @default.
• W4283260025 countsByYear W42832600252023 @default.
• W4283260025 crossrefType "journal-article" @default.
• W4283260025 hasAuthorship W4283260025A5006176014 @default.
• W4283260025 hasAuthorship W4283260025A5015702226 @default.
• W4283260025 hasAuthorship W4283260025A5044565299 @default.
• W4283260025 hasAuthorship W4283260025A5046473582 @default.
• W4283260025 hasAuthorship W4283260025A5048039251 @default.

• next