scholarly journals Revealing the Virulence Potential of Clinical and Environmental Aspergillus fumigatus Isolates Using Whole-Genome Sequencing

2019 ◽  
Vol 10 ◽  
Author(s):  
Fabiola Puértolas-Balint ◽  
John W. A. Rossen ◽  
Claudy Oliveira dos Santos ◽  
Monika M. A. Chlebowicz ◽  
Erwin C. Raangs ◽  
...  
mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Alireza Abdolrasouli ◽  
Johanna Rhodes ◽  
Mathew A. Beale ◽  
Ferry Hagen ◽  
Thomas R. Rogers ◽  
...  

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Roy A. Khalaf ◽  
Nour Fattouh ◽  
Matej Medvecky ◽  
Jaroslav Hrabak

Candida albicans is an opportunistic pathogen accounting for the majority of cases of Candida infections. Currently, C. albicans are developing resistance towards different classes of antifungal drugs and this has become a global health burden that does not spare Lebanon. This study aims at determining point mutations in genes known to be involved in resistance acquisition and correlating resistance to virulence and ergosterol content in the azole resistant C. albicans isolate CA77 from Lebanon. This pilot study is the first of its kind to be implemented in Lebanon. We carried out whole genome sequencing of the azole resistant C. albicans isolate CA77 and examined 18 genes involved in antifungal resistance. To correlate genotype to phenotype, we evaluated the virulence potential of this isolate by injecting it into BALB/c mice and we quantified membrane ergosterol. Whole genome sequencing revealed that eight out of 18 genes involved in antifungal resistance were mutated in previously reported and novel residues. These genotypic changes were associated with an increase in ergosterol content but no discrepancy in virulence potential was observed between our isolate and the susceptible C. albicans control strain SC5314. This suggests that antifungal resistance and virulence potential in this antifungal resistant isolate are not correlated and that resistance is a result of an increase in membrane ergosterol content and the occurrence of point mutations in genes involved in the ergosterol biosynthesis pathway.


PLoS ONE ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. e0225057
Author(s):  
Pragathi B. Shridhar ◽  
Jay N. Worley ◽  
Xin Gao ◽  
Xun Yang ◽  
Lance W. Noll ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e50034 ◽  
Author(s):  
Simone M. T. Camps ◽  
Bas E. Dutilh ◽  
Maiken C. Arendrup ◽  
Antonius J. M. M. Rijs ◽  
Eveline Snelders ◽  
...  

2021 ◽  
Vol 10 (1) ◽  
pp. 62
Author(s):  
Giuditta Fiorella Schiavano ◽  
Collins Njie Ateba ◽  
Annalisa Petruzzelli ◽  
Veronica Mele ◽  
Giulia Amagliani ◽  
...  

Listeria monocytogenes (Lm) is the causative agent of human listeriosis. Lm strains have different virulence potential. For this reason, we preliminarily characterised via Whole-Genome Sequencing (WGS) some Lm strains for their key genomic features and virulence-associated determinants, assigning the clonal complex (CC). Moreover, the ability of the same strains to adhere to and invade human colon carcinoma cell line Caco-2, evaluating the possible correspondence with their genetic virulence profile, was also assessed. The clinical strains typed belonged to clonal complex (CC)1, CC31, and CC101 and showed a very low invasiveness. The Lm strains isolated from food were assigned to CC1, CC7, CC9, and CC121. All CC1 carried the hypervirulence pathogenicity island LIPI-3 in addition to LIPI-1. Premature stop codons in the inlA gene were found only in Lm of food origin belonging to CC9 and CC121. The presence of LIPI2_inlII was observed in all the CCs except CC1. The CC7 strain, belonging to an epidemic cluster, also carried the internalin genes inlG and inlL and showed the highest level of invasion. In contrast, the human CC31 strain lacked the lapB and vip genes and presented the lowest level of invasiveness. In Lm, the genetic determinants of hypo- or hypervirulence are not necessarily predictive of a cell adhesion and/or invasion ability in vitro. Moreover, since listeriosis results from the interplay between host and virulence features of the pathogen, even hypovirulent clones are able to cause infection in immunocompromised people.


mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Alireza Abdolrasouli ◽  
Johanna Rhodes ◽  
Mathew A. Beale ◽  
Ferry Hagen ◽  
Thomas R. Rogers ◽  
...  

ABSTRACT A rapid and global emergence of azole resistance has been observed in the pathogenic fungus Aspergillus fumigatus over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves mutations in the cyp51A gene, which encodes a protein targeted by triazole antifungal drugs. Whole-genome sequencing (WGS) was performed for high-resolution single-nucleotide polymorphism (SNP) analysis of 24 A. fumigatus isolates, including azole-resistant and susceptible clinical and environmental strains obtained from India, the Netherlands, and the United Kingdom, in order to assess the utility of WGS for characterizing the alleles causing resistance. WGS analysis confirmed that TR34/L98H (a mutation comprising a tandem repeat [TR] of 34 bases in the promoter of the cyp51A gene and a leucine-to-histidine change at codon 98) is the sole mechanism of azole resistance among the isolates tested in this panel of isolates. We used population genomic analysis and showed that A. fumigatus was panmictic, with as much genetic diversity found within a country as is found between continents. A striking exception to this was shown in India, where isolates are highly related despite being isolated from both clinical and environmental sources across >1,000 km; this broad occurrence suggests a recent selective sweep of a highly fit genotype that is associated with the TR34/L98H allele. We found that these sequenced isolates are all recombining, showing that azole-resistant alleles are segregating into diverse genetic backgrounds. Our analysis delineates the fundamental population genetic parameters that are needed to enable the use of genome-wide association studies to identify the contribution of SNP diversity to the generation and spread of azole resistance in this medically important fungus. IMPORTANCE Resistance to azoles in the ubiquitous ascomycete fungus A. fumigatus was first reported from clinical isolates collected in the United States during the late 1980s. Over the last decade, an increasing number of A. fumigatus isolates from the clinic and from nature have been found to show resistance to azoles, suggesting that resistance is emerging through selection by the widespread usage of agricultural azole antifungal compounds. Aspergillosis is an emerging clinical problem, with high rates of treatment failures necessitating the development of new techniques for surveillance and for determining the genome-wide basis of azole resistance in A. fumigatus.


2018 ◽  
Author(s):  
Mark Stevenson ◽  
Alistair T Pagnamenta ◽  
Heather G Mack ◽  
Judith A Savige ◽  
Kate E Lines ◽  
...  

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