Photochemical interaction of dictamnine, a furoquinoline alkaloid, with fungal DNA in vitro and in vivo

1982 ◽  
Vol 28 (5) ◽  
pp. 468-473 ◽  
Author(s):  
Gaby E. Pfyffer ◽  
G. H. Neil Towers

The furoquinoline alkaloid dictamnine has been shown to provoke lethal damage to filamentous fungi in near ultraviolet light. The phototoxicity was more pronounced against Mucor hiemalis and Mucor ramannianus than against Fusarium graminearum and Penicillium italicum. In vitro, labeled dictamnine was shown to form covalent monoadducts with purified DNA from M. hiemalis in the presence of long-wave ultraviolet light. Addition of [3H]dictamnine to cultures of the same organism showed photobinding with the fungal DNA in vivo. These results support the suggestion made earlier, on the basis of in vitro experiments with calf thymus DNA, that DNA represents a major cellular target in vivo for the phototoxicity of the alkaloid.

Author(s):  
Fernando Dip ◽  
Pedro Bregoli ◽  
Jorge Falco ◽  
Kevin P. White ◽  
Raúl J. Rosenthal

2013 ◽  
Vol 76 (10) ◽  
pp. 1761-1766 ◽  
Author(s):  
GÜLTEN TİRYAKİ GÜNDÜZ ◽  
FIKRET PAZIR

In this study, the effects of UV-C on two of the main wound pathogens of citrus fruits, Penicillium digitatum and Penicillium italicum, were investigated with different inoculation methods in vitro and on oranges. P. digitatum and P. italicum spores were inoculated onto the surface of potato dextrose agar or oranges using spread, spot, wound, and piercing inoculation methods. UV-C treatment for 1 min from a working distance of 8 cm reduced the numbers of P. italicum and P. digitatum by about 3.9 and 5.3 log units, respectively, following spread inoculation under in vitro conditions. Significant reductions were obtained after 1-min UV-C treatments of the tested fungi following inoculation using the spread and spot methods. With inoculation by the wound and piercing methods, the tested spores were not inactivated completely even after 10- and 20-min treatment times, respectively. The application of UV-C (7.92 kJ m−2) on oranges reduced the percentage of oranges infected at least threefold compared with the rate of infection in the untreated control samples. UV-C irradiation could effectively inactivate spores of P. italicum and P. digitatum inoculated by the spread plate and spot inoculation methods under in vitro and in vivo conditions. On the other hand, because of the low penetration ability of UV-C light, the tested fungi were not completely inactivated following inoculation with the wound and piercing methods. UV-C treatment has potential for use in surface decontamination of citrus fruits.


Author(s):  
S. Seyedmousavi ◽  
Y. C. Chang ◽  
J. H. Youn ◽  
D. Law ◽  
M. Birch ◽  
...  

Clinically relevant members of the Scedosporium / Pseudallescheria species complex and Lomentospora prolificans are generally resistant against currently available systemic antifungal agents in vitro and the infection due to these species is difficult to treat. We studied the in vivo efficacy of a new fungicidal agent olorofim (formerly F901318) against scedosporiosis and lomentosporiosis in neutropenic animals. Cyclophosphamide immunosuppressed CD-1 mice infected by Scedosporium apiospermum , Pseudallescheria boydii ( Scedosporium boydii ) and Lomentospora prolificans were treated by intraperitoneal administration of olorofim (15 mg/kg every 8 h for 9 days). The efficacy of olorofim treatment was assessed by the survival rate at 10 days post infection, levels of serum (1-3)-β-d-glucan (BG), histopathology, and fungal burden of kidneys 3 days post infection. Olorofim therapy significantly improved survival compared to the untreated controls; 80%, 100% and 100% of treated mice survived infection by Scedosporium apiospermum , Pseudallescheria boydii , and Lomentospora prolificans, respectively while less than 20% of the control mice (PBS-treated) survived at 10 days post infection. In the olorofim-treated neutropenic CD-1 mice infected with all three species, serum BG levels were significantly suppressed and fungal DNA detected in the target organs was significantly lower than controls. Furthermore, histopathology of kidneys revealed no or only few lesions with hyphal elements in the olorofim-treated mice, while numerous fungal hyphae were present in control mice. These results indicate olorofim to be a promising therapeutic agent for systemic scedosporiosis/lomentosporiosis, a devastating emerging fungal infection difficult to treat with currently available antifungals.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1179-1179 ◽  
Author(s):  
Janine M. Lamonica ◽  
Christopher R. Vakoc ◽  
Gerd A. Blobel

Abstract All three hematopoietic GATA transcription factors GATA-1, GATA-2, and GATA-3 are acetylated, although the in vivo role of this modification remains unclear. It has been proposed that acetylation of GATA-1 increases its affinity for DNA in vitro, although this finding has not been observed by others. To study the role of GATA-1 acetylation, we examined the functions of an acetylation-defective mutant of GATA-1 in maturing erythroid cells. We found that removal of the acetylation sites in GATA-1 largely abrogates its biological activity but does not impair its nuclear localization, steady state protein levels, or its ability to bind naked GATA elements in vitro. However, chromatin immunoprecipitation (ChIP) experiments revealed that mutant GATA-1 was dramatically impaired in binding to its cellular target sites in vivo, including genes that are normally activated (α- and β-globin, EKLF, FOG-1, Band3, and AHSP) and repressed (GATA-2 and c-kit) by GATA-1. Together, these results suggest that acetylation is required for GATA-1 chromatin occupancy. These findings point to a novel function for transcription factor acetylation, perhaps by facilitating protein interactions required for stable association with chromatin templates in vivo. To identify proteins that interact with acetylated GATA-1, we performed peptide affinity chromatography using acetylated GATA-1 peptides. Using this technique coupled with mass spectrometry, several proteins that bind to GATA-1 peptides in an acetylation-dependent manner were identified. The identified proteins contain known acetyl-lysine binding modules (bromodomains) consistent with their binding properties. The in vivo role of these proteins with regard to GATA-1 function is being examined and will be discussed.


1974 ◽  
Vol 19 (5) ◽  
pp. 321-328 ◽  
Author(s):  
Harold Werbin ◽  
Bala D. Lakchaura ◽  
John Jagger

1984 ◽  
Vol 98 (4) ◽  
pp. 1291-1295 ◽  
Author(s):  
H D Shine ◽  
R L Sidman

Shiverer (shi) is an autosomal recessive mutation in mice that results in hypomyelination in the central nervous system (CNS) but normal myelination in the peripheral nervous system (PNS). Myelin basic proteins (MBPs) are virtually absent in both PNS and CNS. It is not known whether the cellular target in the PNS is the myelin-forming Schwann cell or another cell type which secondarily affects the Schwann cell. To determine the cellular target of the shi gene, we have adapted tissue culture techniques that allow co-culture of pure populations of mouse sensory neurons of one genotype with Schwann cells and fibroblasts of another genotype under conditions that permit myelin formation. These cultures were stained immunocytochemically as whole mounts to determine whether MBPs were expressed under various in vitro conditions. In single-genotype cultures, presence or absence of MBPs was consistent with earlier in vivo results: +/+ cultures were MBP-positive and shi/shi cultures were MBP-negative. In mixed-genotype cultures, visualization of MBPs in myelin accorded with the genotype of the non-neuronal Schwann cells and fibroblasts and not with the neurons--those cultures that contained +/+ non-neuronal cells were MBP-positive and those with shi/shi non-neuronal cells were MBP-negative, independent of the neuronal genotype. These results rule out neurons or circulating substances as mediators of the influence of the shi genetic locus on MBP synthesis and deposition in peripheral myelin.


1992 ◽  
Vol 70 (8) ◽  
pp. 1563-1569 ◽  
Author(s):  
P. Halama ◽  
L. Lacoste

Perithecial formation of Phaeosphaeria nodorum is obtained in vitro on sterilized wheat straws, under strict conditions of light and temperature. The absence of any reproductive form in the dark indicates photoinduction. The different parameters of light (duration, quality, and intensity) influence perithecial morphogenesis. A 12-h photoperiod, near ultraviolet light (300 nm < λ < 400 nm), and intensities of 400 and 600 μW/cm2 are the most favourable conditions for perithecial differentiation. The perithecial production occurs best at 10 °C, is markedly reduced at 14 °C, and absent above 14 °C. Light and temperature have a sequential influence on the successive stages of perithecial development. Whereas primordial formation is photoinhibited and cryostimulated, transformation to the early stage of perithecial development is photoinduced and not affected by temperatures of 10 and 18 °C. The subsequent stages up to ascogenesis are photostimulated and cryoinduced, and ascosporogenesis is photoindependent and cryostimulated. Key words: Phaeosphaeria, Leptosphaeria nodorum, perithecia, light, temperature.


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