Abstract:
:We previously observed that hypoxia is an important component of host microenvironments during pulmonary fungal infections. However, mechanisms of fungal growth in these in vivo hypoxic conditions are poorly understood. Here, we report that mitochondrial respiration is active in hypoxia (1% oxygen) and critical for fungal pathogenesis. We generated Aspergillus fumigatus alternative oxidase (aoxA) and cytochrome C (cycA) null mutants and assessed their ability to tolerate hypoxia, macrophage killing and virulence. In contrast to ΔaoxA, ΔcycA was found to be significantly impaired in conidia germination, growth in normoxia and hypoxia, and displayed attenuated virulence. Intriguingly, loss of cycA results in increased levels of AoxA activity, which results in increased resistance to oxidative stress, macrophage killing and long-term persistence in murine lungs. Thus, our results demonstrate a previously unidentified role for fungal mitochondrial respiration in the pathogenesis of aspergillosis, and lay the foundation for future research into its role in hypoxia signalling and adaptation.
journal_name
Mol Microbioljournal_title
Molecular microbiologyauthors
Grahl N,Dinamarco TM,Willger SD,Goldman GH,Cramer RAdoi
10.1111/j.1365-2958.2012.08034.xsubject
Has Abstractpub_date
2012-04-01 00:00:00pages
383-99issue
2eissn
0950-382Xissn
1365-2958journal_volume
84pub_type
杂志文章abstract::NADPH oxidases (Nox) produce reactive oxygen species (ROS) in multicellular eukaryotic organisms. They trigger defense reactions ('oxidative burst') - in phagocytes and plant cells -, and are involved in a broad range of differentiation processes. Fungal Nox-complexes play a central role in vegetative, sexual and path...
journal_title:Molecular microbiology
pub_type: 杂志文章
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abstract::In Escherichia coli, the SeqA protein is known as a negative regulator of chromosome replication. This protein is also suggested to have a role in chromosome organization. SeqA preferentially binds to hemi-methylated DNA and is by immunofluorescence microscopy seen as foci situated at the replication factories. Loss o...
journal_title:Molecular microbiology
pub_type: 杂志文章
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更新日期:2004-10-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章
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更新日期:1993-10-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章
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journal_title:Molecular microbiology
pub_type: 杂志文章
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更新日期:1993-08-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2005.04595.x
更新日期:2005-05-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.1990.tb00629.x
更新日期:1990-04-01 00:00:00
abstract::We have built a homology model of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli based on the crystal structure of the hexamerization domain of N-ethylmaleimide-sensitive fusion protein. The resulting model of the hexameric ring of the ATP-bound form of the AAA ATPase suggests a plausible mechan...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.2001.02301.x
更新日期:2001-02-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2958.1992.tb01417.x
更新日期:1992-09-01 00:00:00
abstract::The fibronectin binding protein, FnBPA, is a multifunctional microbial surface component recognizing adhesive matrix molecule (MSCRAMM) that promotes bacterial adherence to immobilized fibrinogen and elastin via the N-terminal A domain. The binding site for fibrinogen and elastin was localized to subdomains N2N3. A th...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2006.05552.x
更新日期:2007-02-01 00:00:00
abstract::The classic expression pattern of the Fis global regulatory protein during batch culture consists of a high peak in the early logarithmic phase of growth, followed by a sharp decrease through mid-exponential growth phase until Fis is almost undetectable at the end of the exponential phase. We discovered that this patt...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2007.05916.x
更新日期:2007-10-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.1998.00745.x
更新日期:1998-03-01 00:00:00
abstract::In this work, we have studied the in vitro translational features of a bicistronic mRNA of the extremely thermophilic Archaeon Sulfolobus solfataricus, with the aim of determining the nature of the cis-acting signals controlling the recognition of the translation initiation sites in the Archaea. We found that the most...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.1999.01615.x
更新日期:1999-10-01 00:00:00
abstract::A challenge common to all bacterial pathogens is to acquire nutrients from hostile host environments. Iron is an important cofactor required for essential cellular processes such as DNA repair, energy production and redox balance. Within a mammalian host, most iron is sequestered within heme, which in turn is predomin...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/mmi.14270
更新日期:2019-08-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2007.05616.x
更新日期:2007-03-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.1993.tb01667.x
更新日期:1993-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2003-10-01 00:00:00
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journal_title:Molecular microbiology
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更新日期:2013-03-01 00:00:00
abstract::The Incl1 conjugative plasmid Collb-P9 carries a psiB gene that prevents induction of the SOS response in host bacteria. This locus is located 2.5 kb downstream of the ssb (single-stranded DNA-binding protein) gene in the leading region. This portion of Collb is strikingly similar to part of the leading region of the ...
journal_title:Molecular microbiology
pub_type: 杂志文章
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更新日期:1992-03-01 00:00:00
abstract::Pseudomonas aeruginosa can express two distinct forms of lipopolysaccharide (LPS), called A-band and B-band. As an attempt to understand the molecular biology of the synthesis and regulation of these LPS antigens, a recombinant plasmid, pFV3, containing genes for A-band expression was isolated previously. In the prese...
journal_title:Molecular microbiology
pub_type: 杂志文章
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更新日期:1993-05-01 00:00:00
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journal_title:Molecular microbiology
pub_type: 杂志文章
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更新日期:2013-12-01 00:00:00
abstract::The Caulobacter crescentus flagellum serves not only as a motility apparatus, but also as a key landmark in the differentiation of this asymmetrically dividing bacterium. A distinctive aspect of flagellum biosynthesis is the periodic expression of the flagellar genes during the cell cycle in a sequence corresponding t...
journal_title:Molecular microbiology
pub_type: 杂志文章,评审
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更新日期:1997-04-01 00:00:00
abstract::Metal ions are crucial trace elements for bacteria infecting the human host. The LraI (lipoprotein receptor-associated antigen I) transporter in Streptococcus spp. belongs to the superfamily of ABC transporters. The transporter consists of a lipoprotein, an ATP-binding protein and a hydrophobic integral membrane prote...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.1999.01626.x
更新日期:1999-11-01 00:00:00
abstract::A growing class of proteins regulates transcription through interaction with DNA-dependent RNA polymerase. Here we report that a recently identified, highly conserved sporulation gene ylyA encodes a novel RNA polymerase-binding protein that influences the expression of genes under the control of the late-acting, sporu...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/mmi.12262
更新日期:2013-07-01 00:00:00
abstract::The DnaA protein, which initiates chromosomal replication in Escherichia coli, is negatively regulated by both the sliding clamp of DNA polymerase III holoenzyme and the IdaB protein. We have found that, when the amount of minichromosome is limited in an in vitro replication system, minichromosomal replication-stimula...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.2001.02378.x
更新日期:2001-04-01 00:00:00
abstract::The bacterial actin homologue MreB forms a helix underneath the cytoplasmic membrane and was shown to be essential in the morphogenesis of the rod-shaped cells. Additionally, MreB was implicated to be involved in DNA segregation. However, in our hands the mreBCD deletion strain (PA340-678) grew without apparent DNA se...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2007.05777.x
更新日期:2007-07-01 00:00:00