scholarly journals β(1-3)Glucanosyltransferase Gel4p Is Essential for Aspergillus fumigatus

2010 ◽  
Vol 9 (8) ◽  
pp. 1294-1298 ◽  
Author(s):  
Amandine Gastebois ◽  
Thierry Fontaine ◽  
Jean-Paul Latgé ◽  
Isabelle Mouyna

ABSTRACT The β(1-3)glucanosyltransferase GEL family of Aspergillus fumigatus contains 7 genes, among which only 3 are expressed during mycelial growth. The role of the GEL4 gene was investigated in this study. Like the other Gelps, it encodes a glycosylphosphatidylinositol (GPI)-anchored protein. In contrast to the other β(1-3)glucanosyltransferases analyzed to date, it is essential for this fungal species.

2016 ◽  
Vol 60 (9) ◽  
pp. 5420-5426 ◽  
Author(s):  
Florencia Leonardelli ◽  
Daiana Macedo ◽  
Catiana Dudiuk ◽  
Matias S. Cabeza ◽  
Soledad Gamarra ◽  
...  

ABSTRACTAspergillus fumigatusintrinsic fluconazole resistance has been demonstrated to be linked to theCYP51Agene, although the precise molecular mechanism has not been elucidated yet. Comparisons betweenA. fumigatusCyp51Ap andCandida albicansErg11p sequences showed differences in amino acid residues already associated with fluconazole resistance inC. albicans. The aim of this study was to analyze the role of the natural polymorphism I301 inAspergillus fumigatusCyp51Ap in the intrinsic fluconazole resistance phenotype of this pathogen. The I301 residue inA. fumigatusCyp51Ap was replaced with a threonine (analogue to T315 atCandida albicansfluconazole-susceptible Erg11p) by changing one single nucleotide in theCYP51Agene. Also, aCYP51Aknockout strain was obtained using the same parental strain. Both mutants' antifungal susceptibilities were tested. The I301T mutant exhibited a lower level of resistance to fluconazole (MIC, 20 μg/ml) than the parental strain (MIC, 640 μg/ml), while no changes in MIC were observed for other azole- and non-azole-based drugs. These data strongly implicate theA. fumigatusCyp51Ap I301 residue in the intrinsic resistance to fluconazole.


2015 ◽  
Vol 70 (1) ◽  
pp. 24-42 ◽  
Author(s):  
Pietro Beritelli ◽  
Federica Buffa ◽  
Umberto Martini

Purpose – The purpose of this paper is to present an alternative perspective on understanding the coordinating role of destination management organizations. Destination Management Organizations (DMOs) are known to have a coordinating role within a destination. Many qualitative case studies discuss this role in the institutional context, assuming that the DMO is supposed to coordinate the network of the organizations and stakeholder groups in the destination. By contrast, this paper analyzes the coordinator role of DMOs by focusing primarily on the prominent individuals (directors and board members) affiliated with it. In so doing, it proposes an alternative perspective on these organizations. Looking at the influential individuals in the destination, in particular those affiliated with the DMO, reveals new insights into what the DMO alternatively could be from an individual’s perspective. Design/methodology/approach – Using social network analysis, the coordinator role of the actors affiliated with the DMO for six destination cases in Switzerland, Italy and Austria was measured. First, the network of the most salient individuals in the destination was identified. Second, the coordinator score with the help of the Gould and Fernandez measure was measured. Third, the coordinator scores of individuals affiliated with the DMO were compared against those of the other actors in the network. Fourth, the scores of actors affiliated with the DMO and other actors were compared to the coordinator role attributed to the whole organization by those individuals (i.e. how they see the DMO as coordinator). Fifth, the analysis of the results with case-specific information was completed. Findings – In each of the six destinations, there are actors affiliated with the DMO as top scorers; these are usually the president of the board and other board members, as well as the director. Additionally, the analysis identifies further board members of the DMO among the tourist elite in the destination. The DMO as an organization is generally seen as an important coordinating institution. In particular, the actors affiliated with the DMO attribute a higher coordinating role to the organization than do the other respondents. Practical implications – In their board constellation, DMOs support the formation of interlocking directorships through the representation of various stakeholder groups. They increase the concentration of power in favor of a small group (elite), but they can also increase the effectiveness of decisional processes. In so doing, a DMO serves as a valuable platform for leaders in its destination. Social implications – This study affords a surprising insight into the difference between the overall image actors have of DMOs and the organizations’ self-images, expressed by the actors affiliated to the organizations – the former is always lower than the latter. The study also clearly demonstrates that the role of an institution largely depends on the actors affiliated to it and hence points to the constantly adapting coordinating role of DMOs within destinations. Originality/value – A DMO can be seen as an organization constituted by individuals who join and leave its board or its management. This paper proposes an actor-based analysis of these often small, but controversially discussed organizations. We do it with a combination of quantitative measures from network analysis and qualitative information. The alternative perspective (actors of the DMOs inside the elite) and the application of social network analysis for this purpose have not been used in studies before. Further research points to two new research streams, namely, to understanding the role attributed to the DMO by different actors in the destination and the reasons for joining/leaving the organization and the shift of the self-concept of the DMO.


2010 ◽  
Vol 9 (5) ◽  
pp. 774-783 ◽  
Author(s):  
Edyta Szewczyk ◽  
Sven Krappmann

ABSTRACT Sexual reproduction of the human pathogen Aspergillus fumigatus (teleomorph: Neosartorya fumigata) was assumed to be absent or cryptic until recently, when fertile crosses among geographically restricted environmental isolates were described. Here, we provide evidence for mating, fruiting body development, and ascosporogenesis accompanied by genetic recombination between unrelated, clinical isolates of A. fumigatus, and this evidence demonstrates the generality and reproducibility of this long-time-undisclosed phase in the life cycle of this heterothallic fungus. Successful mating requires the presence of both mating-type idiomorphs MAT1-1 and MAT1-2, as does expression of genes encoding factors presumably involved in this process. Moreover, analysis of an A. fumigatus mutant deleted for the nsdD gene suggests a role of this conserved regulator of cleistothecium development in hyphal fusion and hence heterokaryon formation.


2011 ◽  
Vol 80 (1) ◽  
pp. 410-417 ◽  
Author(s):  
Melissa A. Gessner ◽  
Jessica L. Werner ◽  
Lauren M. Lilly ◽  
Michael P. Nelson ◽  
Allison E. Metz ◽  
...  

ABSTRACTWe have previously reported that mice deficient in the beta-glucan receptor Dectin-1 displayed increased susceptibility toAspergillus fumigatuslung infection in the presence of lower interleukin 23 (IL-23) and IL-17A production in the lungs and have reported a role for IL-17A in lung defense. As IL-23 is also thought to control the production of IL-22, we examined the role of Dectin-1 in IL-22 production, as well as the role of IL-22 in innate host defense againstA. fumigatus. Here, we show that Dectin-1-deficient mice demonstrated significantly reduced levels of IL-22 in the lungs early afterA. fumigatuschallenge. Culturing cells from enzymatic lung digestsex vivofurther demonstrated Dectin-1-dependent IL-22 production. IL-22 production was additionally found to be independent of IL-1β, IL-6, or IL-18 but required IL-23. The addition of recombinant IL-23 augmented IL-22 production in wild-type (WT) lung cells and rescued IL-22 production by lung cells from Dectin-1-deficient mice.In vivoneutralization of IL-22 in the lungs of WT mice resulted in impairedA. fumigatuslung clearance. Moreover, mice deficient in IL-22 also demonstrated a higher lung fungal burden afterA. fumigatuschallenge in the presence of impaired IL-1α, tumor necrosis factor alpha (TNF-α), CCL3/MIP-1α, and CCL4/MIP-1β production and lower neutrophil recruitment, yet intact IL-17A production. We further show that lung lavage fluid collected from bothA. fumigatus-challenged Dectin-1-deficient and IL-22-deficient mice had compromised anti-fungal activity againstA. fumigatus in vitro. Although lipocalin 2 production was observed to be Dectin-1 and IL-22 dependent, lipocalin 2-deficient mice did not demonstrate impairedA. fumigatusclearance. Moreover, lungS100a8,S100a9, andReg3gmRNA expression was not lower in either Dectin-1-deficient or IL-22-deficient mice. Collectively, our results indicate that early innate lung defense againstA. fumigatusis mediated by Dectin-1-dependent IL-22 production.


2012 ◽  
Vol 56 (6) ◽  
pp. 3277-3282 ◽  
Author(s):  
Martina Bielaszewska ◽  
Evgeny A. Idelevich ◽  
Wenlan Zhang ◽  
Andreas Bauwens ◽  
Frieder Schaumburg ◽  
...  

ABSTRACTThe role of antibiotics in treatment of enterohemorrhagicEscherichia coli(EHEC) infections is controversial because of concerns about triggering hemolytic-uremic syndrome (HUS) by increasing Shiga toxin (Stx) production. During the recent large EHEC O104:H4 outbreak, antibiotic therapy was indicated for some patients. We tested a diverse panel of antibiotics to which the outbreak strain is susceptible to interrogate the effects of subinhibitory antibiotic concentrations on induction ofstx2-harboring bacteriophages,stx2transcription, and Stx2 production in this emerging pathogen. Ciprofloxacin significantly increasedstx2-harboring phage induction and Stx2 production in outbreak isolates (Pvalues of <0.001 to <0.05), while fosfomycin, gentamicin, and kanamycin insignificantly influenced them (P> 0.1) and chloramphenicol, meropenem, azithromycin, rifaximin, and tigecycline significantly decreased them (P≤ 0.05). Ciprofloxacin and chloramphenicol significantly upregulated and downregulatedstx2transcription, respectively (P< 0.01); the other antibiotics had insignificant effects (P> 0.1). Meropenem, azithromycin, and rifaximin, which were used for necessary therapeutic or prophylactic interventions during the EHEC O104:H4 outbreak, as well as tigecycline, neither inducedstx2-harboring phages nor increasedstx2transcription or Stx2 production in the outbreak strain. These antibiotics might represent therapeutic options for patients with EHEC O104:H4 infection if antibiotic treatment is inevitable. We await further analysis of the epidemic to determine if usage of these agents was associated with an altered risk of developing HUS.


2007 ◽  
Vol 6 (9) ◽  
pp. 1552-1561 ◽  
Author(s):  
Janyce A. Sugui ◽  
Julian Pardo ◽  
Yun C. Chang ◽  
Arno Müllbacher ◽  
Kol A. Zarember ◽  
...  

ABSTRACT The alb1 (pksP) gene has been reported as a virulence factor controlling the pigmentation and morphology of conidia in Aspergillus fumigatus. A recent report suggested that laeA regulates alb1 expression and conidial morphology but not pigmentation in the A. fumigatus strain AF293. laeA has also been reported to regulate the synthesis of secondary metabolites, such as gliotoxin. We compared the role of laeA in the regulation of conidial morphology and the expression of alb1 and gliP in strains B-5233 and AF293, which differ in colony morphology and nutritional requirements. Deletion of laeA did not affect conidial morphology or pigmentation in these strains, suggesting that laeA is not involved in alb1 regulation during conidial morphogenesis. Deletion of laeA, however, caused down-regulation of alb1 during mycelial growth in a liquid medium. Transcription of gliP, involved in the synthesis of gliotoxin, was drastically reduced in B-5233laeAΔ, and the gliotoxin level found in the culture filtrates was 20% of wild-type concentrations. While up-regulation of gliP in AF293 was comparable to that in B-5233, the relative mRNA level in AF293laeAΔ was about fourfold lower than that in B-5233laeAΔ. Strain B-5233laeAΔ caused slower onset of fatal infection in mice relative to that with B-5233. Histopathology of sections from lungs of infected mice corroborated the survival data. Culture filtrates from B-5233laeAΔ caused reduced death in thymoma cells and were less inhibitory to a respiratory burst of neutrophils than culture filtrates from B-5233. Our results suggest that while laeA is not involved in the regulation of alb1 function in conidial morphology, it regulates the synthesis of gliotoxin and the virulence of A. fumigatus.


2014 ◽  
Vol 81 (4) ◽  
pp. 1234-1241 ◽  
Author(s):  
Jordyn Bergsveinson ◽  
Nina Baecker ◽  
Vanessa Pittet ◽  
Barry Ziola

ABSTRACTSpecific isolates of lactic acid bacteria (LAB) can grow in the harsh beer environment, thus posing a threat to brew quality and the economic success of breweries worldwide. Plasmid-localized genes, such ashorA,horC, andhitA, have been suggested to confer hop tolerance, a trait required for LAB survival in beer. The presence and expression of these genes among LAB, however, do not universally correlate with the ability to grow in beer. Genome sequencing of the virulent beer spoilage organismLactobacillus brevisBSO 464 revealed the presence of eight plasmids, with plasmids 1, 2, and 3 containinghorA,horC, andhitA, respectively. To investigate the roles that these and the other five plasmids play inL. brevisBSO 464 growth in beer, plasmid curing with novobiocin was used to derive 10 plasmid variants. Multiplex PCRs were utilized to determine the presence or absence of each plasmid, and how plasmid loss affected hop tolerance and growth in degassed (noncarbonated) beer was assessed. Loss of three of the eight plasmids was found to affect hop tolerance and growth in beer. Loss of plasmid 2 (horCand 28 other genes) had the most dramatic effect, with loss of plasmid 4 (120 genes) and plasmid 8 (47 genes) having significant, but smaller, impacts. These results support the contention that genes on mobile genetic elements are essential for bacterial growth in beer and that beer spoilage ability is not dependent solely on the three previously described hop tolerance genes or on the chromosome of a beer spoilage LAB isolate.


mSphere ◽  
2022 ◽  
Author(s):  
E. M. Keizer ◽  
I. D. Valdes ◽  
B. L. McCann ◽  
E. M. Bignell ◽  
H. A. B. Wösten ◽  
...  

Opportunistic pathogens like Aspergillus fumigatus have strategies to protect themselves against reactive oxygen species like hydrogen peroxides and superoxides that are produced by immune cells. DHN-melanin is the green pigment on conidia of Aspergillus fumigatus and more than 2 decades ago was reported to protect conidia against hydrogen peroxide.


2019 ◽  
Vol 42 (12) ◽  
pp. 1333-1352 ◽  
Author(s):  
Jongseon Lee ◽  
Nami Kim

Purpose This paper aims to examine whether balancing exploration and exploitation rather than emphasizing one over the other leads to better performance. This study also examines the effects of different kinds of external collaboration on a firm’s performance in relation to the firm’s current innovative direction that shows firms’ internal weighting of exploration or exploitation. Design/methodology/approach Data on Korean manufacturing firms collected from the Korean Innovation Survey were used to test the hypotheses. This study suggested the concept of innovative direction (θ) to examine current innovation capabilities about how much the firms focused on exploration or exploitation. The directionality of exploration or exploitation has not been reflected in previous measures of ambidexterity. Factor analysis and hierarchical regression were used to test hypotheses. Findings The findings suggest that balancing exploration and exploitation is beneficial for a firm’s performance, and explorative collaboration is more beneficial for firms internally emphasizing exploitation. However, it showed that for exploration-oriented firms, exploitative collaboration does not supplement exploitative activities. Research limitations/implications Inter-organizational collaboration helps to develop ambidexterity that leads to better performance. Because inter-organizational collaboration involves substantial costs and is time-consuming, selecting and maintaining partners has to be conducted carefully. Based on the currently pursuing innovative directions, firms can make more appropriate decision for finding external cooperative partners with much of efficiency. When firms find collaborative partners, it is the first thing to look inside themselves. Originality/value Previous studies mainly focused on the selection and balance of the partnership between exploration and exploitation without considering the role of an internal innovative strategy firms are currently pursuing. Identifying firms’ current states and finding partners that can supplement any deficiencies provides the most efficient option for the ambidextrous organization. Consideration of inter-organizational collaborations based on the analysis of internal conditions will be fruitful for the study of ambidexterity.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Michela Loi ◽  
Barbara Barbieri ◽  
Manuel Castriotta ◽  
Maria Chiara Di Guardo

PurposePrior studies on entrepreneurial intention have shown that different orientations exist regarding entrepreneurial engagement: one looking at the growth of a venture (growth-oriented) and the other looking at the maintenance of an entrepreneurial autonomy (independence-oriented). Filling a gap in the literature concerning the reasons why individuals develop different orientations of entrepreneurial intention, this study revolves around achievement goal motivation (mastery, performance and avoidance approaches) and self-regulatory modes (locomotion and assessment), since both are thought to be at the origin and maintenance of an action willingness.Design/methodology/approachIn a sample of 209 undergraduates, we administered a structured questionnaire at the beginning of an elective entrepreneurship education programme. Through a set of hierarchical regressions we examined the specific role of achievement goal motivation and regulatory modes in relation to the two orientations of intention.FindingsOur findings show that, on the one hand, growth-oriented intention is related to a performance approach and both locomotion and assessment regulatory modes. On the other hand, independence-oriented intention is related to an avoidance approach.Research limitations/implicationsThese results illuminate the theoretical connections between entrepreneurial intention and motivation and provide implications for entrepreneurship education and the relationship between intention and consequent behaviour.Originality/valueThis study is among the first to provide an empirical exploration of the motivational and regulatory drivers that lie beneath a growth-oriented and an independent-oriented intention, offering a theoretical explanation about the development of different intentions towards venture creation. Our findings illuminate on the urgency to consider entrepreneurial intention as a multi-dimensional construct if we are to understand the intention-behaviour nexus.


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