The pathogenicity of<i>Aspergillus fumigatus</i>, drug resistance, and nanoparticle delivery

Szalewski, David A.; Hinrichs, Victoria S.; Zinniel, Denise K.; Barletta, Raúl G.

doi:10.1139/cjm-2017-0749

Cited by 37 publications

(21 citation statements)

References 145 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although this study focused on polymorphisms in genes cyp51A and fks1, there is also increasing research on non-cyp51 (Zakaria et al, 2020) and non-fks1 (Szalewski et al, 2018) genetic changes. Future exploitation of genomic data on strains of A. fumigatus and closely related species could also exploit these additional genes.…”

Section: Discussionmentioning

confidence: 99%

Genomic and Phenotypic Heterogeneity of Clinical Isolates of the Human Pathogens Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus fumigatiaffinis

et al. 2020

View full text Add to dashboard Cite

Fungal pathogens are a global threat to human health. For example, fungi from the genus Aspergillus cause a spectrum of diseases collectively known as aspergillosis. Most of the >200,000 life-threatening aspergillosis infections per year worldwide are caused by Aspergillus fumigatus. Recently, molecular typing techniques have revealed that aspergillosis can also be caused by organisms that are phenotypically similar to A. fumigatus but genetically distinct, such as Aspergillus lentulus and Aspergillus fumigatiaffinis. Importantly, some of these so-called cryptic species are thought to exhibit different virulence and drug susceptibility profiles than A. fumigatus, however, our understanding of their biology and pathogenic potential has been stymied by the lack of genome sequences and phenotypic profiling of multiple clinical strains. To fill this gap, we phenotypically characterized the virulence and drug susceptibility of 15 clinical strains of A. fumigatus, A. lentulus, and A. fumigatiaffinis from Spain and sequenced their genomes. We found heterogeneity in drug susceptibility across species and strains. We further found heterogeneity in virulence within each species but no significant differences in the virulence profiles between the three species. Genes known to influence drug susceptibility (cyp51A and fks1) vary in paralog number and sequence among these species and strains and correlate with differences in drug susceptibility. Similarly, genes known to be important for virulence in A. fumigatus showed variability in number of paralogs across strains and across species. Characterization of the genomic similarities and differences of clinical strains of A. lentulus, A. fumigatiaffinis, and A. fumigatus that vary in disease-relevant traits will advance our understanding of the variance in pathogenicity between Aspergillus species and strains that are collectively responsible for the vast majority of aspergillosis infections in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Genomic and Phenotypic Heterogeneity of Clinical Isolates of the Human Pathogens Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus fumigatiaffinis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Aspergillus fumigatus is an important and deadly pathogen to humans. They are the dominating cause of aspergillosis, responsible for high human morbidity and mortality on a global basis . Besides this, they are also used to produce a large number of industrial enzymes, organic acids, and pharmaceuticals .…”

Section: Discussionmentioning

confidence: 99%

“…The structure was solved in P4 1 2 1 2 space group with unit-cell parameters a = b = 152. 31 A, c = 133.20 A, a = b = c = 90.00°. A trimer was found in the asymmetric unit with a Matthews' coefficient of 7.…”

Section: Effects Of Organic Solvents and Detergents On Lipase Activitmentioning

confidence: 99%

Structure and characterization of Aspergillus fumigatus lipase B with a unique, oversized regulatory subdomain

et al. 2019

View full text Add to dashboard Cite

Fungal lipases are efficient and environment‐friendly biocatalysts for many industrially relevant processes. One of the most widely applied lipases in the manufacturing industry is Candida antarctica lipase B (CALB). Here, we report the biochemical and structural characterization of a novel CALB‐like lipase from an important human pathogen—Aspergillus fumigatus (AFLB), which has high sn‐1,3‐specificity toward triolein. AFLB crystal structure displays a CALB‐like catalytic domain and hosts a unique tightly closed ‘lid’ domain that contains a disulfide bridge, as well as an extra N‐terminal subdomain composed of residues 1–128 (including the helix α1–α5 located above the active site). To gain insight into the function of this novel lid and N‐terminal subdomain, we constructed and characterized a series of mutants in these two domains. Deleting the protruding bulk lid's residues, replacing the bulk and tight lid with a small and loose lid from CALB, or breaking the disulfide bridge increased the affinity of CALB for glyceride substrates and improved its catalytic activity, along with the loss of enzyme fold stability and thermostability. N‐terminal truncation mutants revealed that the N‐terminal peptide (residues 1–59) is a strong inhibitor of AFLB binding to lipid films. This peptide thus limits AFLB's penetration power and specific activity, revealing a unique enzyme activity regulatory mechanism. Our findings on the functional and structural properties of AFLB provide a better understanding of the functions of the CALB‐like lipases and pave the way for its future protein engineering. Database Structural data are available in the Protein Data Bank under the accession numbers http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6IDY.

show abstract

“…Additionally, some pathogenic contaminations contained in the biological EcM material may also provoke severe immune rejection and foreign body response in preliminary xenografts (7). They are divided into two major categories: Viral particles/elements and salmonella (8). The former is particularly problematic in terms of xenozoonoses, including brucellosis, leptospirosis, and tularellosis.…”

Section: Extracellular Matrix Grafts: From Preparation To Applicationmentioning

confidence: 99%

Extracellular matrix grafts: From preparation to application (Review)

Jiang

Han

et al. 2020

Int J Mol Med

View full text Add to dashboard Cite

Recently, the increasing emergency of traffic accidents and the unsatisfactory outcome of surgical intervention are driving research to seek a novel technology to repair traumatic soft tissue injury. From this perspective, decellularized matrix grafts (ECM-G) including natural ECM materials, and their prepared hydrogels and bioscaffolds, have emerged as possible alternatives for tissue engineering and regenerative medicine. Over the past decades, several physical and chemical decellularization methods have been used extensively to deal with different tissues/organs in an attempt to carefully remove cellular antigens while maintaining the non-immunogenic ECM components. It is anticipated that when the decellularized biomaterials are seeded with cells in vitro or incorporated into irregularly shaped defects in vivo , they can provide the appropriate biomechanical and biochemical conditions for directing cell behavior and tissue remodeling. The aim of this review is to first summarize the characteristics of ECM-G and describe their major decellularization methods from different sources, followed by analysis of how the bioactive factors and undesired residual cellular compositions influence the biologic function and host tissue response following implantation. Lastly, we also provide an overview of the in vivo application of ECM-G in facilitating tissue repair and remodeling.

show abstract

The pathogenicity ofAspergillus fumigatus, drug resistance, and nanoparticle delivery

Cited by 37 publications

References 145 publications

Genomic and Phenotypic Heterogeneity of Clinical Isolates of the Human Pathogens Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus fumigatiaffinis

Genomic and Phenotypic Heterogeneity of Clinical Isolates of the Human Pathogens Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus fumigatiaffinis

Structure and characterization of Aspergillus fumigatus lipase B with a unique, oversized regulatory subdomain

Extracellular matrix grafts: From preparation to application (Review)

Contact Info

Product

Resources

About