Alteration of Cell Wall Composition Leads to Amphotericin B Resistance in <i>Aspergillus flavus</i>

Seo, Kuniko; Akiyoshi, Hiroto; Ohnishi, Yoshinari

doi:10.1111/j.1348-0421.1999.tb01231.x

Cited by 80 publications

(55 citation statements)

References 46 publications

(24 reference statements)

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“…Ergosterol levels are reported to be the main cause for resistance to this drug, with both increased as well as decreased levels of ergosterol being correlated with amphotericin B sensitivity (Pasrija et al, 2005;Sanglard et al, 2003). In many reports of fungal resistance to this drug, there have also been increases in chitin or glucan levels (Bahmed et al, 2002;Seo et al, 1999). However, in Candida there is at least one report that correlates amphotericin B resistance with decreased chitin levels (Bahmed et al, 2003).…”

Section: Discussionmentioning

confidence: 93%

The Candida albicans homologue of PIG-P, CaGpi19p: gene dosage and role in growth and filamentation

2010

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Glycosylphosphatidyl inositol (GPI)-anchored proteins in Candida albicans are responsible for a vast range of functions, and deletions in certain GPI-anchored proteins severely reduce adhesion and virulence of this organism. In addition, completely modified GPIs are necessary for virulence. GPI anchor biosynthesis is essential for viability and starts with the transfer of N-acetylglucosamine to phosphatidylinositol. This step is catalysed by a multi-subunit complex, GPI–N-acetylglucosaminyltransferase (GPI–GnT). In this, the first report to our knowledge on a subunit of the Candida GPI–GnT complex, we show that CaGpi19p is the functional equivalent of the Saccharomyces cerevisiae Gpi19p. An N-terminal truncation mutant of CaGpi19p functionally complements a conditionally lethal S. cerevisiae gpi19 mutant. Further, we constructed a conditional null mutant of CaGPI19 by disrupting one allele and placing the remaining copy under the control of the MET3 promoter. Repression leads to growth defects, cell wall biogenesis aberrations, azole sensitivity and hyperfilamention. In addition, there is a noticeable gene dosage effect, with the heterozygote also displaying intermediate degrees of most phenotypes. The mutants also displayed a reduced susceptibility to the antifungal agent amphotericin B. Collectively, the results suggest that CaGPI19 is required for normal morphology and cell wall architecture.

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Section: Discussionmentioning

confidence: 93%

The Candida albicans homologue of PIG-P, CaGpi19p: gene dosage and role in growth and filamentation

2010

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“…Although the true rate of AmB resistance is unknown, some investigators have reported isolates of A. flavus resistant to AmB in vitro (Odds et al, 1998;Lass-Florl et al, 1998;Seo et al, 1999;Mosquera et al, 2001;Gomez-Lopez et al, 2003;Sutton et al, 2004;Hsueh et al, 2005), although this is not universally accepted. In a study from Taiwan (Hsueh et al, 2005) isolates of A. flavus and A. fumigatus with reduced susceptibilities to AmB were found (MICs 2 mg ml 21 ).…”

Section: Amphotericin Bmentioning

confidence: 99%

Aspergillus flavus: human pathogen, allergen and mycotoxin producer

et al. 2007

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Aspergillus infections have grown in importance in the last years. However, most of the studies have focused on Aspergillus fumigatus, the most prevalent species in the genus. In certain locales and hospitals, Aspergillus flavus is more common in air than A. fumigatus, for unclear reasons. After A. fumigatus, A. flavus is the second leading cause of invasive aspergillosis and it is the most common cause of superficial infection. Experimental invasive infections in mice show A. flavus to be 100-fold more virulent than A. fumigatus in terms of inoculum required. Particularly common clinical syndromes associated with A. flavus include chronic granulomatous sinusitis, keratitis, cutaneous aspergillosis, wound infections and osteomyelitis following trauma and inoculation. Outbreaks associated with A. flavus appear to be associated with single or closely related strains, in contrast to those associated with A. fumigatus. In addition, A. flavus produces aflatoxins, the most toxic and potent hepatocarcinogenic natural compounds ever characterized. Accurate species identification within Aspergillus flavus complex remains difficult due to overlapping morphological and biochemical characteristics, and much taxonomic and population genetics work is necessary to better understand the species and related species. The flavus complex currently includes 23 species or varieties, including two sexual species, Petromyces alliaceus and P. albertensis. The genome of the highly related Aspergillus oryzae is completed and available; that of A. flavus in the final stages of annotation. Our understanding of A. flavus lags far behind that of A. fumigatus. Studies of the genomics, taxonomy, population genetics, pathogenicity, allergenicity and antifungal susceptibility of A. flavus are all required.

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“…Rapid identification of molds causing invasive disease could facilitate the timely administration of effective therapy. For example, Aspergillus flavus and Aspergillus terreus have been reported to be resistant to amphotericin B (39,45), and Aspergillus fumigatus can become resistant to itraconazole (9).…”

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confidence: 99%

Multilocus DNA Sequence Comparisons Rapidly Identify Pathogenic Molds

Rakeman¹,

Bui²,

LaFe³

et al. 2005

J Clin Microbiol

119

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The increasing incidence of opportunistic fungal infections necessitates rapid and accurate identification of the associated fungi to facilitate optimal patient treatment. Traditional phenotype-based identification methods utilized in clinical laboratories rely on the production and recognition of reproductive structures, making identification difficult or impossible when these structures are not observed. We hypothesized that DNA sequence analysis of multiple loci is useful for rapidly identifying medically important molds. Our study included the analysis of the D1/D2 hypervariable region of the 28S ribosomal gene and the internal transcribed spacer (ITS) regions 1 and 2 of the rRNA operon. Two hundred one strains, including 143 clinical isolates and 58 reference and type strains, representing 43 recognized species and one possible new species, were examined. We generated a phenotypically validated database of 118 diagnostic alleles. DNA length polymorphisms detected among ITS1 and ITS2 PCR products can differentiate 20 of 33 species of molds tested, and ITS DNA sequence analysis permits identification of all species tested. For 42 of 44 species tested, conspecific strains displayed >99% sequence identity at ITS1 and ITS2; sequevars were detected in two species. For all 44 species, identifications by genotypic and traditional phenotypic methods were 100% concordant. Because dendrograms based on ITS sequence analysis are similar in topology to 28S-based trees, we conclude that ITS sequences provide phylogenetically valid information and can be utilized to identify clinically important molds. Additionally, this phenotypically validated database of ITS sequences will be useful for identifying new species of pathogenic molds.

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Alteration of Cell Wall Composition Leads to Amphotericin B Resistance in Aspergillus flavus

Cited by 80 publications

References 46 publications

The Candida albicans homologue of PIG-P, CaGpi19p: gene dosage and role in growth and filamentation

The Candida albicans homologue of PIG-P, CaGpi19p: gene dosage and role in growth and filamentation

Aspergillus flavus: human pathogen, allergen and mycotoxin producer

Multilocus DNA Sequence Comparisons Rapidly Identify Pathogenic Molds

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