Candida haemulonii Complex and Candida auris: Biology, Virulence Factors, Immune Response, and Multidrug Resistance

Gómez-Gaviria, Manuela; Martínez-Álvarez, José A.; Chávez-Santiago, Joaquín O; Mora-Montes, Héctor M.

doi:10.2147/idr.s402754

Cited by 21 publications

(17 citation statements)

References 135 publications

(256 reference statements)

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“…Both the C. haemulonii species complex and C. auris are well-known for their intrinsic multidrug-resistance profiles to clinically available antifungal agents, particularly azoles and polyenes, which challenges clinicians to achieve successful treatments. This scenario is worsened by the medical condition of the affected individuals, who generally have a compromised immunological system and/or severe underlying illnesses such as diabetes, pulmonary, renal, and peripheral vascular diseases [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Cell Aggregation Capability of Clinical Isolates from Candida auris and Candida haemulonii Species Complex

et al. 2023

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The opportunistic fungal pathogens belonging to the Candida haemulonii complex and the phylogenetically related species Candida auris are well-known for causing infections that are difficult to treat due to their multidrug-resistance profiles. Candida auris is even more worrisome due to its ability to cause outbreaks in healthcare settings. These emerging yeasts produce a wide range of virulence factors that facilitate the development of the infectious process. In recent years, the aggregative phenotype has been receiving attention, as it is mainly associated with defects in cellular division and its possible involvement in helping the fungus to escape from the host immune responses. In the present study, we initially investigated the aggregation ability of 18 clinical isolates belonging to the C. haemulonii species complex (C. haemulonii sensu stricto, C. duobushaemulonii, and C. haemulonii var. vulnera) and C. auris. Subsequently, we evaluated the effects of physicochemical factors on fungal aggregation competence. The results demonstrated that cell-to-cell aggregation was a typically time-dependent event, in which almost all studied fungal isolates of both the C. haemulonii species complex and C. auris exhibited high aggregation after 2 h of incubation at 37 °C. Interestingly, the fungal cells forming the aggregates remained viable. The aggregation of all isolates was not impacted by pH, temperature, β-mercaptoethanol (a protein-denaturing agent), or EDTA (a chelator agent). Conversely, proteinase K, trypsin, and sodium dodecyl sulfate (SDS) significantly diminished the fungal aggregation. Collectively, our results demonstrated that the aggregation ability of these opportunistic yeast pathogens is time-dependent, and surface proteins and hydrophobic interactions seem to mediate cell aggregation since the presence of proteases and anionic detergents affected the aggregation capability. However, further studies are necessary to better elucidate the molecular aspects of this intriguing phenomenon.

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Section: Introductionmentioning

confidence: 99%

Cell Aggregation Capability of Clinical Isolates from Candida auris and Candida haemulonii Species Complex

et al. 2023

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“…To identify pathogenic associated genes among the set of orthologs in these species, we used two previously curated gene catalogues [ 49 50 ]. These lists include 629 genes of C. albicans that have been implicated in different aspects of pathogenicity such as hyphae and biofilm formation, adhesion, evasion of the immune system and invasion of the host (Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…Genes associated with pathogenicity were obtained from previously curated catalogues in C. albicans (33 genes from [ 49 ], 674 from [ 50 ] resulting in a set 629 genes) (Table S1, available in the online version of this article). ALS, TLO and SAP genes were obtained from Jackson et al ., [ 3 ] and Oh et al ., [ 51 ].…”

Section: Methodsmentioning

confidence: 99%

Genetic modification of Candida maltosa, a non-pathogenic CTG species, reveals EFG1 function

Chávez-Tinoco,

García-Ortega,

Mancera

2024

Microbiology

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Candida maltosa is closely related to important pathogenic Candida species, especially C. tropicalis and C. albicans, but it has been rarely isolated from humans. For this reason, through comparative studies, it could be a powerful model to understand the genetic underpinnings of the pathogenicity of Candida species. Here, we generated a cohesive assembly of the C. maltosa genome and developed genetic engineering tools that will facilitate studying this species at a molecular level. We used a combination of short and long-read sequencing to build a polished genomic draft composed of 14 Mbp, 45 contigs and close to 5700 genes. This assembly represents a substantial improvement from the currently available sequences that are composed of thousands of contigs. Genomic comparison with C. albicans and C. tropicalis revealed a substantial reduction in the total number of genes in C. maltosa. However, gene loss seems not to be associated to the avirulence of this species given that most genes that have been previously associated with pathogenicity were also present in C. maltosa. To be able to edit the genome of C. maltosa we generated a set of triple auxotrophic strains so that gene deletions can be performed similarly to what has been routinely done in pathogenic Candida species. As a proof of concept, we generated gene knockouts of EFG1, a gene that encodes a transcription factor that is essential for filamentation and biofilm formation in C. albicans and C. tropicalis. Characterization of these mutants showed that Efg1 also plays a role in biofilm formation and filamentous growth in C. maltosa, but it seems to be a repressor of filamentation in this species. The genome assembly and auxotrophic mutants developed here are a key step forward to start using C. maltosa for comparative and evolutionary studies at a molecular level.

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“…To identify pathogenic associated genes among the set of orthologs in these species we used two previously curated gene catalogs (Gómez-Gaviria et al, 2023; Noble et al, 2010). These lists include 629 genes of C. albicans that have been implicated in different aspects of pathogenicity such as hyphae and biofilm formation, adhesion, evasion of the immune system and invasion of the host (Supplementary Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Genes associated with pathogenicity were obtained from previously curated catalogs in C. albicans (33 genes from Gómez-Gaviria et al, 2023, and674 from Noble et al, 2010) resulting in a set 629 genes. ALS, TLO and SAP genes were obtained from Jackson et al, (2009) and Oh et al, (2019).…”

Section: Identification Of Genes Associated With Pathogenicitymentioning

confidence: 99%

Genetic modification ofCandida maltosa, a nonpathogenic CTG species, revealsEFG1function

Chávez-Tinoco,

García-Ortega,

Mancera

2023

Preprint

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Candida maltosais closely related to important pathogenicCandidaspecies, but it has been rarely isolated from humans. Therefore, through comparative studies, it could be a powerful model to understand the pathogenicity underpinnings ofCandidaspecies. To facilitate studyingC. maltosaat a molecular level, we built a cohesive genomic sequence composed of 45 scaffolds, a substantial improvement from the thousands of contigs of the available draft. Comparison withC. albicansandC. tropicalisrevealed a reduction in the total number of genes inC. maltosa. However, gene loss seems not to be associated to its avirulence given that most pathogenicity genes were also present inC. maltosa. To genetically editC. maltosawe generated triple auxotrophic strains so that gene deletions can be performed as has been routinely done in pathogenic species. As a proof of concept, we generated gene knockouts of Efg1, a transcription regulator involved in filamentation and biofilm formation in pathogenic species. Although inC. maltosaEfg1 also played a role in these processes, it seems to rather be a repressor of filamentation. The genome assembly and auxotrophic mutants developed are a key step to start usingC. maltosafor comparative studies at a molecular level.

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Candida haemulonii Complex and Candida auris: Biology, Virulence Factors, Immune Response, and Multidrug Resistance

Cited by 21 publications

References 135 publications

Cell Aggregation Capability of Clinical Isolates from Candida auris and Candida haemulonii Species Complex

Cell Aggregation Capability of Clinical Isolates from Candida auris and Candida haemulonii Species Complex

Genetic modification of Candida maltosa, a non-pathogenic CTG species, reveals EFG1 function

Genetic modification ofCandida maltosa, a nonpathogenic CTG species, revealsEFG1function

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