Usefulness of the Non-conventional Caenorhabditis elegans Model to Assess Candida Virulence

Ortega-Riveros, Marcelo; De-la-Pinta, Iker; Marcos‐Arias, Cristina; Ezpeleta, Guillermo; Quindós, Guillermo; Eraso, Elena

doi:10.1007/s11046-017-0142-8

Cited by 25 publications

(23 citation statements)

References 52 publications

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“…Despite mice being an excellent model to study pathogenicity and virulence of fungi, use of this model is facing ethical conflict and economic issues [86]. Since the innate immune system is evolutionary conserved in insects, invertebrate organisms such as Drosophila melanogaster [85], Caenorhabditis elegans [87,88] Tenebrio molitor [89] and Galleria mellonella [86] are gaining interest as models for studying virulence traits of Candida species and host response against Candida infections.…”

Section: Candida Auris Virulence In Vivomentioning

confidence: 99%

Attack, Defend and Persist: How the Fungal Pathogen Candida auris was Able to Emerge Globally in Healthcare Environments

Jong

Hagen

2019

Mycopathologia

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Within a decade after its first description, the multidrug-resistant yeast Candida auris has emerged globally as a nosocomial pathogen causing difficult to control outbreaks. This, together with the alarmingly high mortality rate of up to 66% associated with C. auris candidemia, calls for a better understanding of its virulence traits and routes of transmission. Unlike other clinically relevant Candida species, C. auris seems to have the unique ability to be easily transmitted between patients. Although initially thought to express fewer virulence traits than Candida albicans, recent genomic insights suggest C. auris to possess these traits to a much more similar extent. This review highlights the virulence traits C. auris expresses to attack the host, defend itself against antimicrobial agents and to persist within the healthcare environment.

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Section: Candida Auris Virulence In Vivomentioning

confidence: 99%

Attack, Defend and Persist: How the Fungal Pathogen Candida auris was Able to Emerge Globally in Healthcare Environments

Jong

Hagen

2019

Mycopathologia

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“…Ltd (Xi'an, Shaanxi, China, the equipment was ExiProgen from BIONEER). (Figure 1 and [35]. In the future, we hope to discover new broad-spectrum antimicrobial drugs against MRSA.…”

Section: Preparation Of Antibacterial Peptides In the Brevinin-2 Familymentioning

confidence: 99%

“…Finally, the association between Brevinin-2 family numbers and the DAF-2/DAF-16 pathway of C. elegans was verified by the lys-7 relative expression level (mRNA and protein). We revealed the important role of the conserved innate immunity signaling pathway of DAF-2/DAF-16 by analyzing host-peptide interactions in the C. elegans model [35]. In the future, we hope to discover new broad-spectrum antimicrobial drugs against MRSA.…”

Section: Introductionmentioning

confidence: 98%

Brevinin-2 Drug Family—New Applied Peptide Candidates Against Methicillin-Resistant Staphylococcus aureus and Their Effects on Lys-7 Expression of Innate Immune Pathway DAF-2/DAF-16 in Caenorhabditis elegans

et al. 2018

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The issue of Staphylococcus aureus (MRSA) developing a resistance to drugs such as methicillin has long been the focus for new drug development. In recent years, antimicrobial peptides, such as small molecular peptides with broad-spectrum antibacterial activity and special antibacterial mechanism, have shown a strong medicinal potential. In particular, the Brevinin-2 family has been shown to have a significant inhibitory effect against gram-positive bacteria (G+). In this study, we researched the influence of MRSA on the behavior and survival rate of nematodes. We established an assay of Caenorhabditis elegans–MRSA antimicrobial peptides to screen for new potent anti-infective peptides against MRSA. From the Brevinin-2 family, 13 peptides that had shown strong effects on G+ were screened for their ability to prolong the lifespan of infected worms. Real-time Polymerase Chain Reaction (PCR) tests were used to evaluate the effect on the innate immune pathway dauer formation defective (DAF)-2/DAF-16 of C. elegans. The assay successfully screened and filtered out four of the 13 peptides that significantly improved the survival rate of MRSA-infected worms. The result of real-time PCR indicated that the mRNA and protein expression levels of lys-7 were consistently upregulated by being treated with four of the Brevinin-2 family. The Brevinin-2 family peptides, including Brevinin-2, Brevinin-2-OA3, Brevinin-2ISb, and Brevinin-2TSa, also played an active role in the DAF-2/DAF-16 pathway in C. elegans. We successfully demonstrated the utility of anti-infective peptides that prolong the survival rate of the MRSA-infected host and discovered the relationship between antibacterial peptides and the innate immune system of C. elegans. We demonstrated the antimicrobial effects of Brevinin-2 family peptides, indicating their potential for use as new drug candidates against MRSA infections.

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“…The most commonly employed invertebrate species include the nematode Caenorhabditis elegans , the fly Drosophila melanogaster , and larvae of the Greater Wax moth Galleria mellonella . All three species can be easily maintained in the laboratory at a much lower cost than mice or rabbits and have been successfully used for the study of diverse yeast pathogens, such as C. neoformans 15,16 , C. albicans 16–18 , C. parapsilosis 18–20 , C. glabrata 19,21 . Of note, invertebrate models differ in their applicability and the best suitable model should be carefully selected 22 .…”

Section: Introductionmentioning

confidence: 99%

Tobacco Hornworm (Manduca sexta) caterpillars as a novel host model for the study of fungal virulence and drug efficacy

Lyons

Softley

Balfour

et al. 2019

Preprint

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29Pathogenic yeast species can cause life-threatening infections in humans. The two leading 30 yeast pathogens, Candida albicans and Cryptococcus neoformans, cause systemic infections 31 in >1.4 million patients world-wide with mortality rates approaching 75%. It is thus 32 imperative to study fungal virulence mechanisms, stress response pathways, and the efficacy 33 of antifungal drugs. This is commonly done using mammalian models. To address ethical and 34 practical concerns, invertebrate models, such as wax moth larvae, nematodes, or flies, have 35 been introduced over the last two decades. To address short-comings in existing invertebrate 36 host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca 37 sexta as a novel host model for the study of fungal virulence and drug efficacy. These 38 caterpillars can be raised at standardised conditions, maintained at 37˚C, can be injected with 39 defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, 40 including C. albicans, C. neoformans, C. auris, and C. glabrata. Infected caterpillars can be 41 rescued by treatment with commonly deployed antifungal drugs and importantly, fungal 42 burden can be assessed daily throughout the course of infection in a single caterpillar's faeces 43 and hemolymph. Notably, these animals are large enough so that weight provides a reliable 44 and reproducible measure of fungal virulence. This model combines a suite of parameters that 45 recommend it for the study of fungal virulence. 46 47 50 tuberculosis 1 . The leading yeast pathogens, Candida albicans and Cryptococcus neoformans, 51 together account for >1,400,000 life-threatening infections world-wide with mortality rates 52 approaching 75% 1 . Candidemia, most commonly caused by C. albicans, is the fourth most 53 common cause of nosocomial blood stream infections, only surpassed by infections with 54Staphylococci and Enterococcus spp. Disturbingly, candidemia incidence rates are on the 55 rise. Within less than ten years, incidence rates increased by 36% 2 . Although cryptococcosis 56 incidence rates are on the decline in North America, this AIDS-defining illness is responsible 57 for 15% of all AIDS-related deaths world-wide 2,3 . This already dire situation is further 58 confounded by the emergence of drug resistant yeast species. Patients at risk of developing 59 invasive candidemia are often prophylactically treated with fluconazole, while the 60 echinocandins are considered a first line defence strategy 4 . Yet, C. glabrata, the most 61 3 common non-albicans Candida species associated with nosocomial blood stream infections 5 , 62 is intrinsically less susceptible to azole drugs and acquires resistance to echinocandins 63 rapidly 6 . The rapid global spread of multi-drug resistant C. auris has further exacerbated the 64 threat posed by fungi. C. auris was first reported in 2009 in Japan 7 . In 2015, C. auris arrived 65 in Europe causing an outbreak involving 72 patients in a cardio-thoracic hospital i...

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Usefulness of the Non-conventional Caenorhabditis elegans Model to Assess Candida Virulence

Cited by 25 publications

References 52 publications

Attack, Defend and Persist: How the Fungal Pathogen Candida auris was Able to Emerge Globally in Healthcare Environments

Attack, Defend and Persist: How the Fungal Pathogen Candida auris was Able to Emerge Globally in Healthcare Environments

Brevinin-2 Drug Family—New Applied Peptide Candidates Against Methicillin-Resistant Staphylococcus aureus and Their Effects on Lys-7 Expression of Innate Immune Pathway DAF-2/DAF-16 in Caenorhabditis elegans

Tobacco Hornworm (Manduca sexta) caterpillars as a novel host model for the study of fungal virulence and drug efficacy

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