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Michael A Pfaller - One of the best experts on this subject based on the ideXlab platform.
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analysis of global antifungal surveillance results reveals predominance of erg11 y132f alteration among azole resistant Candida parapsilosis and Candida tropicalis and country specific isolate dissemination
International Journal of Antimicrobial Agents, 2020Co-Authors: Mariana Castanheira, Paul R Rhomberg, S A Messer, Lalitagauri M Deshpande, Michael A PfallerAbstract:ABSTRACT This study evaluated the activity of echinocandins, azoles and amphotericin B against Candida spp. isolates and other yeasts and characterised azole resistance mechanisms in Candida parapsilosis and Candida tropicalis. Invasive Candida spp. isolates (n = 2936) collected in 60 hospitals worldwide during 2016–2017 underwent antifungal susceptibility testing by broth microdilution. Azole-resistant C. parapsilosis and C. tropicalis were submitted to qPCR for ERG11, CDR1 and MDR1, and the whole genome sequence was analysed. Results of non-susceptibility to echinocandins ranged from 0.0–2.3%, being highest in Candida glabrata. More than 99.0% of the Candida albicans isolates were susceptible to both fluconazole and voriconazole. Fluconazole resistance in C. glabrata was 6.5% overall, being highest in the USA (13.0%). Resistance to voriconazole in Candida krusei was only noted in the USA (5.0%). Azoles inhibited 89.1–91.6% of C. parapsilosis isolates, with most resistant isolates noted in Europe (15.1%), including 36 isolates from Italy (three hospitals), of which 34 harboured Erg11 Y132F mutations and overexpressed MDR1. Azole non-wild-type C. tropicalis (7/227) were found in five countries: 3 isolates from Thailand had the same Erg11 Y132F alteration. Fluconazole non-wild-type isolates were noted among 3/77 (3.9%) Candida dubliniensis, 4/17 (23.5%) Candida guilliermondii, 4/47 (8.5%) Candida Lusitaniae and other less common yeast species. Echinocandin use has been recommended over fluconazole for invasive Candida infections. However, azoles are still active against the most common Candida spp. and resistance appears to be restricted to certain geographic regions and associated with Erg11 Y132 alterations in C. parapsilosis and C. tropicalis.
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analysis of global antifungal surveillance results reveals predominance of erg11 y132f alteration among azole resistant Candida parapsilosis and Candida tropicalis and country specific isolate dissemination
International Journal of Antimicrobial Agents, 2020Co-Authors: Mariana Castanheira, Paul R Rhomberg, S A Messer, Lalitagauri M Deshpande, Michael A PfallerAbstract:ABSTRACT This study evaluated the activity of echinocandins, azoles and amphotericin B against Candida spp. isolates and other yeasts and characterised azole resistance mechanisms in Candida parapsilosis and Candida tropicalis. Invasive Candida spp. isolates (n = 2936) collected in 60 hospitals worldwide during 2016–2017 underwent antifungal susceptibility testing by broth microdilution. Azole-resistant C. parapsilosis and C. tropicalis were submitted to qPCR for ERG11, CDR1 and MDR1, and the whole genome sequence was analysed. Results of non-susceptibility to echinocandins ranged from 0.0–2.3%, being highest in Candida glabrata. More than 99.0% of the Candida albicans isolates were susceptible to both fluconazole and voriconazole. Fluconazole resistance in C. glabrata was 6.5% overall, being highest in the USA (13.0%). Resistance to voriconazole in Candida krusei was only noted in the USA (5.0%). Azoles inhibited 89.1–91.6% of C. parapsilosis isolates, with most resistant isolates noted in Europe (15.1%), including 36 isolates from Italy (three hospitals), of which 34 harboured Erg11 Y132F mutations and overexpressed MDR1. Azole non-wild-type C. tropicalis (7/227) were found in five countries: 3 isolates from Thailand had the same Erg11 Y132F alteration. Fluconazole non-wild-type isolates were noted among 3/77 (3.9%) Candida dubliniensis, 4/17 (23.5%) Candida guilliermondii, 4/47 (8.5%) Candida Lusitaniae and other less common yeast species. Echinocandin use has been recommended over fluconazole for invasive Candida infections. However, azoles are still active against the most common Candida spp. and resistance appears to be restricted to certain geographic regions and associated with Erg11 Y132 alterations in C. parapsilosis and C. tropicalis.
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Isavuconazole and Nine Comparator Antifungal Susceptibility Profiles for Common and Uncommon Candida Species Collected in 2012: Application of New CLSI Clinical Breakpoints and Epidemiological Cutoff Values
Mycopathologia, 2014Co-Authors: Mariana Castanheira, Shawn A. Messer, Paul R Rhomberg, Ronald N. Jones, Rachel R. Dietrich, Michael A PfallerAbstract:The in vitro activity of isavuconazole and nine antifungal comparator agents was assessed using reference broth microdilution methods against 1,421 common and uncommon species of Candida from a 2012 global survey. Isolates were identified using CHROMagar, biochemical methods and sequencing of ITS and/or 28S regions. Candida spp. were classified as either susceptible or resistant and as wild type (WT) or non-WT using CLSI clinical breakpoints or epidemiological cutoff values, respectively, for the antifungal agents. Isolates included 1,421 organisms from 21 different species of Candida . Among Candida spp., resistance to all 10 tested antifungal agents was low (0.0–7.9 %). The vast majority of each species of Candida , with the exception of Candida glabrata , Candida krusei , and Candida guilliermondii (modal MICs of 0.5 µg/ml), were inhibited by ≤0.12 µg/ml of isavuconazole (99.0 %; range 94.3 % [ Candida tropicalis ] to 100.0 % [ Candida Lusitaniae and Candida dubliniensis ]). C. glabrata, C. krusei, and C. guilliermondii were largely inhibited by ≤1 µg/ml of isavuconazole (89.7, 96.9 and 92.8 %, respectively). Decreased susceptibility to isavuconazole was most prominent with C. glabrata where the modal MIC for isavuconazole was 0.5 µg/ml for those strains that were SDD to fluconazole or WT to voriconazole, and was 4 µg/ml for those that were either resistant or non-WT to fluconazole or voriconazole, respectively. In conclusion, these data document the activity of isavuconazole and generally the low resistance levels to the available antifungal agents in a large, contemporary (2012), global collection of molecularly characterized species of Candida .
S A Messer - One of the best experts on this subject based on the ideXlab platform.
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analysis of global antifungal surveillance results reveals predominance of erg11 y132f alteration among azole resistant Candida parapsilosis and Candida tropicalis and country specific isolate dissemination
International Journal of Antimicrobial Agents, 2020Co-Authors: Mariana Castanheira, Paul R Rhomberg, S A Messer, Lalitagauri M Deshpande, Michael A PfallerAbstract:ABSTRACT This study evaluated the activity of echinocandins, azoles and amphotericin B against Candida spp. isolates and other yeasts and characterised azole resistance mechanisms in Candida parapsilosis and Candida tropicalis. Invasive Candida spp. isolates (n = 2936) collected in 60 hospitals worldwide during 2016–2017 underwent antifungal susceptibility testing by broth microdilution. Azole-resistant C. parapsilosis and C. tropicalis were submitted to qPCR for ERG11, CDR1 and MDR1, and the whole genome sequence was analysed. Results of non-susceptibility to echinocandins ranged from 0.0–2.3%, being highest in Candida glabrata. More than 99.0% of the Candida albicans isolates were susceptible to both fluconazole and voriconazole. Fluconazole resistance in C. glabrata was 6.5% overall, being highest in the USA (13.0%). Resistance to voriconazole in Candida krusei was only noted in the USA (5.0%). Azoles inhibited 89.1–91.6% of C. parapsilosis isolates, with most resistant isolates noted in Europe (15.1%), including 36 isolates from Italy (three hospitals), of which 34 harboured Erg11 Y132F mutations and overexpressed MDR1. Azole non-wild-type C. tropicalis (7/227) were found in five countries: 3 isolates from Thailand had the same Erg11 Y132F alteration. Fluconazole non-wild-type isolates were noted among 3/77 (3.9%) Candida dubliniensis, 4/17 (23.5%) Candida guilliermondii, 4/47 (8.5%) Candida Lusitaniae and other less common yeast species. Echinocandin use has been recommended over fluconazole for invasive Candida infections. However, azoles are still active against the most common Candida spp. and resistance appears to be restricted to certain geographic regions and associated with Erg11 Y132 alterations in C. parapsilosis and C. tropicalis.
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analysis of global antifungal surveillance results reveals predominance of erg11 y132f alteration among azole resistant Candida parapsilosis and Candida tropicalis and country specific isolate dissemination
International Journal of Antimicrobial Agents, 2020Co-Authors: Mariana Castanheira, Paul R Rhomberg, S A Messer, Lalitagauri M Deshpande, Michael A PfallerAbstract:ABSTRACT This study evaluated the activity of echinocandins, azoles and amphotericin B against Candida spp. isolates and other yeasts and characterised azole resistance mechanisms in Candida parapsilosis and Candida tropicalis. Invasive Candida spp. isolates (n = 2936) collected in 60 hospitals worldwide during 2016–2017 underwent antifungal susceptibility testing by broth microdilution. Azole-resistant C. parapsilosis and C. tropicalis were submitted to qPCR for ERG11, CDR1 and MDR1, and the whole genome sequence was analysed. Results of non-susceptibility to echinocandins ranged from 0.0–2.3%, being highest in Candida glabrata. More than 99.0% of the Candida albicans isolates were susceptible to both fluconazole and voriconazole. Fluconazole resistance in C. glabrata was 6.5% overall, being highest in the USA (13.0%). Resistance to voriconazole in Candida krusei was only noted in the USA (5.0%). Azoles inhibited 89.1–91.6% of C. parapsilosis isolates, with most resistant isolates noted in Europe (15.1%), including 36 isolates from Italy (three hospitals), of which 34 harboured Erg11 Y132F mutations and overexpressed MDR1. Azole non-wild-type C. tropicalis (7/227) were found in five countries: 3 isolates from Thailand had the same Erg11 Y132F alteration. Fluconazole non-wild-type isolates were noted among 3/77 (3.9%) Candida dubliniensis, 4/17 (23.5%) Candida guilliermondii, 4/47 (8.5%) Candida Lusitaniae and other less common yeast species. Echinocandin use has been recommended over fluconazole for invasive Candida infections. However, azoles are still active against the most common Candida spp. and resistance appears to be restricted to certain geographic regions and associated with Erg11 Y132 alterations in C. parapsilosis and C. tropicalis.
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evaluation of the etest method for determining fluconazole susceptibilities of 402 clinical yeast isolates by using three different agar media
Journal of Clinical Microbiology, 1998Co-Authors: M A Pfaller, S A Messer, A Karlsson, A BolmstromAbstract:The performance of the Etest for fluconazole susceptibility testing of 402 yeast isolates was assessed against the National Committee for Clinical Laboratory Standards (NCCLS) microdilution broth method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35°C. Etest MICs were determined with RPMI agar containing 2% glucose (RPG), Casitone agar (CAS), and Mueller-Hinton agar (MHA) and were read after incubation for 48 h at 35°C. The yeast isolates included Candida albicans ( n = 161), Candida glabrata ( n = 41), Candida tropicalis ( n = 35), Candida parapsilosis ( n = 29), Candida krusei ( n = 32), Candida Lusitaniae ( n = 31), Candida species ( n = 19), Cryptococcus neoformans ( n = 40), and miscellaneous yeast species ( n = 14). The Etest results correlated well with reference MICs. Overall agreement was 94% with RPG, 97% with CAS, and 53% with MHA. When RPG was used, agreement ranged from 89% for Candida spp. to 100% for C. krusei . When CAS was utilized, agreement ranged from 93% for Cryptococcus neoformans to 100% for C. tropicalis , C. parapsilosis , C. Lusitaniae , Candida spp., and miscellaneous yeast species. With MHA, agreement ranged from 17% for C. parapsilosis to 90% for C. krusei . Both RPG and CAS supported growth of all yeast species, whereas growth on MHA was comparatively weaker. Etest results were somewhat easier to read on CAS. The Etest method using either RPG or CAS, but not MHA, appears to be a viable alternative to the NCCLS reference method for determining fluconazole susceptibilities of yeasts.
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activity of a new triazole sch 56592 compared with those of four other antifungal agents tested against clinical isolates of Candida spp and saccharomyces cerevisiae
Antimicrobial Agents and Chemotherapy, 1997Co-Authors: M A Pfaller, S A Messer, R N JonesAbstract:Sch 56592 is a new triazole agent with potent, broad-spectrum antifungal activity. The in vitro activities of Sch 56592, itraconazole, fluconazole, amphotericin B, and flucytosine (5-FC) against 404 clinical isolates of Candida spp. (382 isolates) and Saccharomyces cerevisiae (22 isolates) were investigated. In vitro susceptibility testing was performed by a broth microdilution method performed according to National Committee for Clinical Laboratory Standards guidelines. Overall, Sch 56592 was very active (MIC at which 90% of isolates are inhibited [MIC90], 0.5 microgram/ml) against these yeast isolates. Sch 56592 was most active against Candida tropicalis, Candida parapsilosis, Candida Lusitaniae, and Candida stellatoidea (MIC90, < or = 0.12 microgram/ml) and was least active against Candida glabrata (MIC90, 2.0 micrograms/ml). Sch 56592 was 2- to 32-fold more active than amphotericin B and 5-FC against all species except C. glabrata. By comparison with the other triazoles, Sch 56592 was equivalent to itraconazole and greater than or equal to eightfold more active than fluconazole. On the basis of these results, Sch 56592 has promising antifungal activity, and further in vitro and in vivo investigations are warranted.
Mariana Castanheira - One of the best experts on this subject based on the ideXlab platform.
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analysis of global antifungal surveillance results reveals predominance of erg11 y132f alteration among azole resistant Candida parapsilosis and Candida tropicalis and country specific isolate dissemination
International Journal of Antimicrobial Agents, 2020Co-Authors: Mariana Castanheira, Paul R Rhomberg, S A Messer, Lalitagauri M Deshpande, Michael A PfallerAbstract:ABSTRACT This study evaluated the activity of echinocandins, azoles and amphotericin B against Candida spp. isolates and other yeasts and characterised azole resistance mechanisms in Candida parapsilosis and Candida tropicalis. Invasive Candida spp. isolates (n = 2936) collected in 60 hospitals worldwide during 2016–2017 underwent antifungal susceptibility testing by broth microdilution. Azole-resistant C. parapsilosis and C. tropicalis were submitted to qPCR for ERG11, CDR1 and MDR1, and the whole genome sequence was analysed. Results of non-susceptibility to echinocandins ranged from 0.0–2.3%, being highest in Candida glabrata. More than 99.0% of the Candida albicans isolates were susceptible to both fluconazole and voriconazole. Fluconazole resistance in C. glabrata was 6.5% overall, being highest in the USA (13.0%). Resistance to voriconazole in Candida krusei was only noted in the USA (5.0%). Azoles inhibited 89.1–91.6% of C. parapsilosis isolates, with most resistant isolates noted in Europe (15.1%), including 36 isolates from Italy (three hospitals), of which 34 harboured Erg11 Y132F mutations and overexpressed MDR1. Azole non-wild-type C. tropicalis (7/227) were found in five countries: 3 isolates from Thailand had the same Erg11 Y132F alteration. Fluconazole non-wild-type isolates were noted among 3/77 (3.9%) Candida dubliniensis, 4/17 (23.5%) Candida guilliermondii, 4/47 (8.5%) Candida Lusitaniae and other less common yeast species. Echinocandin use has been recommended over fluconazole for invasive Candida infections. However, azoles are still active against the most common Candida spp. and resistance appears to be restricted to certain geographic regions and associated with Erg11 Y132 alterations in C. parapsilosis and C. tropicalis.
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analysis of global antifungal surveillance results reveals predominance of erg11 y132f alteration among azole resistant Candida parapsilosis and Candida tropicalis and country specific isolate dissemination
International Journal of Antimicrobial Agents, 2020Co-Authors: Mariana Castanheira, Paul R Rhomberg, S A Messer, Lalitagauri M Deshpande, Michael A PfallerAbstract:ABSTRACT This study evaluated the activity of echinocandins, azoles and amphotericin B against Candida spp. isolates and other yeasts and characterised azole resistance mechanisms in Candida parapsilosis and Candida tropicalis. Invasive Candida spp. isolates (n = 2936) collected in 60 hospitals worldwide during 2016–2017 underwent antifungal susceptibility testing by broth microdilution. Azole-resistant C. parapsilosis and C. tropicalis were submitted to qPCR for ERG11, CDR1 and MDR1, and the whole genome sequence was analysed. Results of non-susceptibility to echinocandins ranged from 0.0–2.3%, being highest in Candida glabrata. More than 99.0% of the Candida albicans isolates were susceptible to both fluconazole and voriconazole. Fluconazole resistance in C. glabrata was 6.5% overall, being highest in the USA (13.0%). Resistance to voriconazole in Candida krusei was only noted in the USA (5.0%). Azoles inhibited 89.1–91.6% of C. parapsilosis isolates, with most resistant isolates noted in Europe (15.1%), including 36 isolates from Italy (three hospitals), of which 34 harboured Erg11 Y132F mutations and overexpressed MDR1. Azole non-wild-type C. tropicalis (7/227) were found in five countries: 3 isolates from Thailand had the same Erg11 Y132F alteration. Fluconazole non-wild-type isolates were noted among 3/77 (3.9%) Candida dubliniensis, 4/17 (23.5%) Candida guilliermondii, 4/47 (8.5%) Candida Lusitaniae and other less common yeast species. Echinocandin use has been recommended over fluconazole for invasive Candida infections. However, azoles are still active against the most common Candida spp. and resistance appears to be restricted to certain geographic regions and associated with Erg11 Y132 alterations in C. parapsilosis and C. tropicalis.
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Isavuconazole and Nine Comparator Antifungal Susceptibility Profiles for Common and Uncommon Candida Species Collected in 2012: Application of New CLSI Clinical Breakpoints and Epidemiological Cutoff Values
Mycopathologia, 2014Co-Authors: Mariana Castanheira, Shawn A. Messer, Paul R Rhomberg, Ronald N. Jones, Rachel R. Dietrich, Michael A PfallerAbstract:The in vitro activity of isavuconazole and nine antifungal comparator agents was assessed using reference broth microdilution methods against 1,421 common and uncommon species of Candida from a 2012 global survey. Isolates were identified using CHROMagar, biochemical methods and sequencing of ITS and/or 28S regions. Candida spp. were classified as either susceptible or resistant and as wild type (WT) or non-WT using CLSI clinical breakpoints or epidemiological cutoff values, respectively, for the antifungal agents. Isolates included 1,421 organisms from 21 different species of Candida . Among Candida spp., resistance to all 10 tested antifungal agents was low (0.0–7.9 %). The vast majority of each species of Candida , with the exception of Candida glabrata , Candida krusei , and Candida guilliermondii (modal MICs of 0.5 µg/ml), were inhibited by ≤0.12 µg/ml of isavuconazole (99.0 %; range 94.3 % [ Candida tropicalis ] to 100.0 % [ Candida Lusitaniae and Candida dubliniensis ]). C. glabrata, C. krusei, and C. guilliermondii were largely inhibited by ≤1 µg/ml of isavuconazole (89.7, 96.9 and 92.8 %, respectively). Decreased susceptibility to isavuconazole was most prominent with C. glabrata where the modal MIC for isavuconazole was 0.5 µg/ml for those strains that were SDD to fluconazole or WT to voriconazole, and was 4 µg/ml for those that were either resistant or non-WT to fluconazole or voriconazole, respectively. In conclusion, these data document the activity of isavuconazole and generally the low resistance levels to the available antifungal agents in a large, contemporary (2012), global collection of molecularly characterized species of Candida .
Thierry Noel - One of the best experts on this subject based on the ideXlab platform.
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a fox2 dependent fatty acid s oxidation pathway coexists both in peroxisomes and mitochondria of the ascomycete yeast Candida Lusitaniae
PLOS ONE, 2014Co-Authors: Frederic Gabriel, Isabelle Accoceberry, Jeanjacques Bessoule, Benedicte Salin, Marine Lucasguerin, Stephen Manon, Karine Dementhon, Thierry NoelAbstract:It is generally admitted that the ascomycete yeasts of the subphylum Saccharomycotina possess a single fatty acid s-oxidation pathway located exclusively in peroxisomes, and that they lost mitochondrial s-oxidation early during evolution. In this work, we showed that mutants of the opportunistic pathogenic yeast Candida Lusitaniae which lack the multifunctional enzyme Fox2p, a key enzyme of the s-oxidation pathway, were still able to grow on fatty acids as the sole carbon source, suggesting that C. Lusitaniae harbored an alternative pathway for fatty acid catabolism. By assaying 14Cα-palmitoyl-CoA consumption, we demonstrated that fatty acid catabolism takes place in both peroxisomal and mitochondrial subcellular fractions. We then observed that a fox2Δ null mutant was unable to catabolize fatty acids in the mitochondrial fraction, thus indicating that the mitochondrial pathway was Fox2p-dependent. This finding was confirmed by the immunodetection of Fox2p in protein extracts obtained from purified peroxisomal and mitochondrial fractions. Finally, immunoelectron microscopy provided evidence that Fox2p was localized in both peroxisomes and mitochondria. This work constitutes the first demonstration of the existence of a Fox2p-dependent mitochondrial β-oxidation pathway in an ascomycetous yeast, C. Lusitaniae. It also points to the existence of an alternative fatty acid catabolism pathway, probably located in peroxisomes, and functioning in a Fox2p-independent manner.
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inactivation of the fcy2 gene encoding purine cytosine permease promotes cross resistance to flucytosine and fluconazole in Candida Lusitaniae
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: Florence Chapelandleclerc, Julien Bouchoux, Abdelhak Goumar, Christiane Chastin, Jean Villard, Thierry NoelAbstract:In a previous work, we described the possible relationship between a defect of purine-cytosine permease and the acquisition of a cross-resistance to the antifungal combination flucytosine (5FC) and fluconazole (FLC) in Candida Lusitaniae (T. Noel, F. Francois, P. Paumard, C. Chastin, D. Brethes, and J. Villard, Antimicrob. Agents Chemother. 47:1275-1284, 2003). Using degenerate PCR and chromosome walking, we cloned two FCY2-like genes in C. Lusitaniae. Northern blot analysis revealed that only one gene was expressed; it was named FCY2. The other one behaved as a pseudogene and was named FCY21. In order to better characterize the possible role of FCY2 in cross-resistance to 5FC-FLC, disruption experiments with auxotrophic strain 6936 ura3(D95V) FCY2 with an integrative vector carrying the URA3 gene and a partial sequence of the C. Lusitaniae FCY2 gene were undertaken. Southern blot analysis revealed that homologous recombination events occurred in all transformants analyzed at rates of 50% at resident locus FCY2 and 50% at resident locus URA3, resulting in the genotypes ura3 fcy2::URA3 and ura3::URA3 FCY2, respectively. It was then demonstrated that only transformants harboring a disrupted fcy2 gene were resistant to 5FC, susceptible to FLC, and resistant to the 5FC-FLC combination. Finally, complementation experiments with a functional FCY2 gene restored 5FC and FLC susceptibilities to the wild-type levels. The results of this study provide molecular evidence that inactivation of the sole FCY2 gene promotes cross-resistance to the antifungal association 5FC-FLC in C. Lusitaniae.
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development of an integrative transformation system for the opportunistic pathogenic yeast Candida Lusitaniae using ura3 as a selection marker
Yeast, 2004Co-Authors: Fabienne Francois, Florence Chapelandleclerc, Jean Villard, Thierry NoelAbstract:The nucleotide sequence of the URA3 gene encoding orotidine-5'-phosphate decarboxylase (OMP DCase) of the human opportunistic pathogen yeast Candida Lusitaniae was determined by degenerate PCR and chromosome walking. Deduced amino acid sequence showed strong homologies (59-85% identity) with OMP DCases of different Saccharomycetales and allowed identification of the known conserved domains. Very close upstream from the URA3 gene, the 3'-end of a gene encoding a Gea2-like protein was identified. A non-revertible C. Lusitaniae ura3 mutant was selected on the basis of 5-fluoroorotic acid resistance. The mutation was a single point mutation resulting in the amino acid substitution D95V in a highly conserved domain, and in a concomitant EcoRV restriction site polymorphism. The mutant strain was successfully transformed to prototrophy following electroporation with the URA3 gene cloned in an integrative vector, with frequencies of 100-200 transformants per micro g of DNA. Southern blot analysis revealed that almost all transformants were derived from homologous recombination events at the resident locus. The GeneBank Accession No. for C. Lusitaniae URA3 gene is AF450297.
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colony morphology switching of Candida Lusitaniae and acquisition of multidrug resistance during treatment of a renal infection in a newborn case report and review of the literature
Diagnostic Microbiology and Infectious Disease, 2003Co-Authors: Anne Favel, Thierry Noel, Florence Peyron, Annie Michelnguyen, Claude Martin, Laurent Thomachot, Annick Datry, Jeanphilippe Bouchara, Svetlana Challier, Christiane ChastinAbstract:Candida Lusitaniae is an emerging opportunistic pathogen which exhibits an unusual antifungal susceptibility pattern. We describe a case of fatal renal infection due to C. Lusitaniae in a very low birth weight neonate who was treated with short courses of fluconazole given alternately with amphotericin B. A colony morphology switching was detected on the standard primary culture medium by changes in colony size. Switching was shown to affect deeply the susceptibility to amphotericin B. Afterwards, the switched phenotype developed a cross resistance to fluconazole and itraconazole. Several issues raised by this case are discussed in the light of an extensive review of the literature. Our observations point out the importance of both the detection of colony morphology switching and the close monitoring of antifungal susceptibility in the management of infections due to C. Lusitaniae. A judicious therapeutic strategy should prevent the acquisition of multidrug resistance during antifungal therapy.
Racquel Kim Sherwood - One of the best experts on this subject based on the ideXlab platform.
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Convergent Evolution of a Fused Sexual Cycle Promotes the Haploid Lifestyle
2016Co-Authors: Racquel Kim Sherwood, Christine M Scaduto, Ra E. Torres, Richard JAbstract:These authors contributed equally to this work. Sexual reproduction is the prerogative of eukaryotic species and involves the fusion of haploid gametes to form a diploid cell that subsequently undergoes meiosis to generate recombinant haploid forms. This process has been extensively studied in the unicellular yeast Saccharomyces cerevisiae, which exhibits separate regulatory control over mating and meiosis. Here we address the mechanism of sexual reproduction in the related hemiascomycete species Candida Lusitaniae. We demonstrate that in contrast to S. cerevisiae, C. Lusitaniae exhibits a highly integrated sexual program in which the programs regulating mating and meiosis have fused. Profiling of the C. Lusitaniae sexual cycle revealed that gene expression patterns during mating and meiosis were overlapping, suggestive of co-regulation. This was particularly evident for genes involved in pheromone MAPK signaling, which were highly induced throughout the sexual cycle of C. Lusitaniae. Furthermore, genetic analysis showed that the ortholog of IME2, a ‘diploid-specific ’ factor in S. cerevisiae 3,4, and STE12, the master regulator of S. cerevisiae mating5,6, were each required for progression through both mating and meiosis in C. Lusitaniae. Together, ou
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convergent evolution of a fused sexual cycle promotes the haploid lifestyle
Nature, 2014Co-Authors: Racquel Kim Sherwood, Christine M Scaduto, Sandra E Torres, Richard J BennettAbstract:In the predominantly diploid yeast Saccharomyces cerevisiae, regulatory control of mating is separate from meiosis; here the related hemiascomycete yeast Candida Lusitaniae is shown to have coordinated regulatory control of mating and meiosis, favouring the formation of haploids. Sexual reproduction involves the fusion of haploid gametes to form a diploid cell that can subsequently undergo meiosis to generate recombinant haploid forms. In the predominantly diploid yeast Saccharomyces cerevisiae, these processes are regulated separately. Here Richard Bennett and colleagues demonstrate that in the related hemiascomycete yeast Candida Lusitaniae, the mating and meiosis are regulated as one, favouring the formation of haploids. Coordinated mating and meiosis have previously been identified in the more distantly related ascomycete Schizosaccharomyces pombe, suggesting that such a regulatory coupling has evolved multiple times. Sexual reproduction is restricted to eukaryotic species and involves the fusion of haploid gametes to form a diploid cell that subsequently undergoes meiosis to generate recombinant haploid forms. This process has been extensively studied in the unicellular yeast Saccharomyces cerevisiae, which exhibits separate regulatory control over mating and meiosis. Here we address the mechanism of sexual reproduction in the related hemiascomycete species Candida Lusitaniae. We demonstrate that, in contrast to S. cerevisiae, C. Lusitaniae exhibits a highly integrated sexual program in which the programs regulating mating and meiosis have fused. Profiling of the C. Lusitaniae sexual cycle revealed that gene expression patterns during mating and meiosis were overlapping, indicative of co-regulation. This was particularly evident for genes involved in pheromone MAPK signalling, which were highly induced throughout the sexual cycle of C. Lusitaniae. Furthermore, genetic analysis showed that the orthologue of IME2, a ‘diploid-specific’ factor in S. cerevisiae1,2, and STE12, the master regulator of S. cerevisiae mating3,4, were each required for progression through both mating and meiosis in C. Lusitaniae. Together, our results establish that sexual reproduction has undergone significant rewiring between S. cerevisiae and C. Lusitaniae, and that a concerted sexual cycle operates in C. Lusitaniae that is more reminiscent of the distantly related ascomycete, Schizosaccharomyces pombe. We discuss these results in light of the evolution of sexual reproduction in yeast, and propose that regulatory coupling of mating and meiosis has evolved multiple times as an adaptation to promote the haploid lifestyle.
