Candidiasis by Candida glabrata, Candida nivariensis and Candida bracarensis in Galleria mellonella: Virulence and Therapeutic Responses to Echinocandins

Candida albicans is the major etiological agent of invasive candidiasis but the increasing prevalence of emerging species of Candida, such as Candida glabrata and phylogenetically closely related species, Candida nivariensis and Candida bracarensis, requires special attention. Differences in virulence among these species and their therapeutic responses using in vivo non-mammalian models are scarcely analysed. The aim of this study was analyse the survival of G. mellonella and host-pathogen interactions during infection by C. glabrata, C. nivariensis and C. bracarensis. Moreover, therapeutic responses to echinocandins were also assessed in the G. mellonella model of candidiasis. These three species produced lethal infection in G. mellonella; C. glabrata was the most virulent species and C. bracarensis the less. Haemocytes of G. mellonella phagocytised C. bracarensis cells more effectively than those of the other two species. Treatment with caspofungin and micafungin was most effective to protect larvae during C. glabrata and C. nivariensis infections while anidulafungin was during C. bracarensis infection. The model of candidiasis in G. mellonella is simple and appropriate to assess the virulence and therapeutic response of these emerging Candida species. Moreover, it successfully allows for detecting differences in the immune system of the host depending on the virulence of pathogens.

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Galleria mellonella insektua eta Caenorhabditis elegans nematodoa, infekzio eredu boteretsuak Candida glabrata eta erlazionatutako espezieen birulentzia ikertzeko

EKAIA Euskal Herriko Unibertsitateko Zientzi eta Teknologi Aldizkaria ◽

10.1387/ekaia.20323 ◽

2020 ◽

pp. 175-190

Author(s):

Ainara Hernando-Ortiz ◽

Estibaliz Mateo ◽

Marcelo Ortega-Riveros ◽

Iker De-la-Pinta ◽

Guillermo Quindós ◽

...

Keyword(s):

Candida Albicans ◽

Caenorhabditis Elegans ◽

Candida Glabrata ◽

Galleria Mellonella ◽

Candida Bracarensis ◽

Candida Nivariensis

Kandidiasia Candida generoko espezieek eragindako infekzio mikotikoa da. Candida albicans agente etiologiko nagusia da baina gero eta gehiagotan Candida generoko beste espezie batzuk agertzen ari dira kandidiasiaren eragile bezala eta, hauen artean, Candida glabrata espeziea. Espezie honekin lotuta beste bi espezie daude, Candida bracarensis eta Candida nivariensis, teknika molekularrek ondo desberdindu ditzaketenak. Aldaketa etiologiko hauek ondorio larriak izan ditzakete kandidiasiaren diagnostikoan, tratamenduan edota pronostikoan, besteak beste, bere patogenia edo antifungikoekiko sentikortasuna oso desberdina izan daitezkeelako. Ordezko eredu esperimentalek erabiliz mikroorganismoek eragindako gaixotasunen patogenia eta terapia ezagutzeko ezinbesteko aukera ematen dizkigute, eta hauen artean, Caenorhabditis elegans nematodoa eta Galleria mellonella lepidopteroa ditugu. Ikerketa lan honetan konbentzionalak ez diren bi animalia eredu hauen erabilgarritasuna ebaluatu nahi izan da Candida glabrata, Candida bracarensis eta Candida nivariensis harreman filogenetiko estua duten hiru espezie hauen birulentzia in vivo aztertzeko.

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Phagocytic activity of haemocytes from Galleria mellonella larvae infected with Candida glabrata, Candida nivariensis and Candida bracarensis

10.26226/morressier.5ac39995d462b8028d899ca2 ◽

2018 ◽

Author(s):

Ainara Hernando

Keyword(s):

Phagocytic Activity ◽

Candida Glabrata ◽

Galleria Mellonella ◽

Candida Bracarensis ◽

Candida Nivariensis

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Haemocyte responses in Galleria mellonella infected by Candida glabrata, Candida nivariensis and Candida bracarensis

10.26226/morressier.5ac39995d462b8028d899cbd ◽

2018 ◽

Author(s):

Ainara Hernando

Keyword(s):

Candida Glabrata ◽

Galleria Mellonella ◽

Candida Bracarensis ◽

Candida Nivariensis

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Caenorhabditis elegans as a Model System To Assess Candida glabrata, Candida nivariensis, and Candida bracarensis Virulence and Antifungal Efficacy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00824-20 ◽

2020 ◽

Vol 64 (10) ◽

Author(s):

Ainara Hernando-Ortiz ◽

Estibaliz Mateo ◽

Marcelo Ortega-Riveros ◽

Iker De-la-Pinta ◽

Guillermo Quindós ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Candida Glabrata ◽

Model System ◽

Antifungal Drugs ◽

Phenotypic Traits ◽

Content Type ◽

C Elegans ◽

Host Fungus ◽

Candida Bracarensis ◽

Candida Nivariensis

ABSTRACT Although Candida albicans remains the major etiological agent of invasive candidiasis, Candida glabrata and other emerging species of Candida are increasingly isolated. This species is the second most prevalent cause of candidiasis in many regions of the world. However, clinical isolates of Candida nivariensis and Candida bracarensis can be misidentified and are underdiagnosed due to phenotypic traits shared with C. glabrata. Little is known about the two cryptic species. Therefore, pathogenesis studies are needed to understand their virulence traits and their susceptibility to antifungal drugs. The susceptibility of Caenorhabditis elegans to different Candida species makes this nematode an excellent model for assessing host-fungus interactions. We evaluated the usefulness of C. elegans as a nonconventional host model to analyze the virulence of C. glabrata, C. nivariensis, and C. bracarensis. The three species caused candidiasis, and the highest virulence of C. glabrata was confirmed. Furthermore, we determined the efficacy of current antifungal drugs against the infection caused by these species in the C. elegans model. Amphotericin B and azoles showed the highest activity against C. glabrata and C. bracarensis infections, while echinocandins were more active for treating those caused by C. nivariensis. C. elegans proved to be a useful model system for assessing the pathogenicity of these closely related species.

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Efficacies of Fluconazole, Caspofungin, and Amphotericin B in Candida glabrata-Infected p47phox−/− Knockout Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.5.1240-1245.2002 ◽

2002 ◽

Vol 46 (5) ◽

pp. 1240-1245 ◽

Cited By ~ 39

Author(s):

Justina Y. Ju ◽

Cynthia Polhamus ◽

Kieren A. Marr ◽

Steven M. Holland ◽

John E. Bennett

Keyword(s):

Candida Albicans ◽

Amphotericin B ◽

Murine Model ◽

Knockout Mice ◽

Candida Glabrata ◽

Drug Efficacy ◽

Fungal Burden ◽

Lethal Infection

ABSTRACT Candida glabrata is the second leading cause of adult candidemia, resulting in high mortality. Amphotericin B is considered the treatment of choice, while the efficacy of fluconazole is controversial and caspofungin efficacy is unknown. To ascertain drug efficacy in vivo, the utility of a murine model of C. glabrata infection was investigated. C. glabrata was found to cause progressive, lethal infection when injected intravenously into C57BL/6 mice with reduced oxidative microbicidal capacity due to knockout of the p47phox gene. Spleen and kidney organ CFU counts were determined in groups of mice 2 days after the mice completed 6 days of daily intraperitoneal drug treatment, which began on the day of infection. Daily injections of fluconazole at 80 mg/kg did not reduce spleen or kidney CFU counts after infection with C. glabrata strains having in vitro fluconazole MICs of 2, 32, or 256 μg/ml compared to saline-treated controls. However, this fluconazole regimen reduced spleen CFU counts in mice infected with Candida albicans, an infection that is known to be responsive to fluconazole. Caspofungin at 5 mg/kg and amphotericin B at 5 mg/kg were both effective in reducing fungal burden in spleens and kidneys of C. glabrata-infected mice. Ten mice treated for 6 days with caspofungin at 1 mg/kg survived for 15 days, though all 10 saline-injected mice died or were so ill that they had to be sacrificed by 96 h postinfection. This murine model provided evidence of the efficacy of amphotericin B and caspofungin but not of fluconazole against C. glabrata infection.

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In Vitro and In Vivo Activity of Single and Dual Antimicrobial Agents Against KPC-producing Klebsiella pneumoniae

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.936 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S379-S379

Author(s):

Farzad Moussavi ◽

Sarath Nath ◽

Daniel Abraham ◽

David Landman ◽

John Quale

Keyword(s):

Antimicrobial Agents ◽

Galleria Mellonella ◽

Survival Rates ◽

Polymyxin B ◽

The Other ◽

In Vivo Model ◽

Serious Infections ◽

Time Kill

Abstract Background Options for treatment of infections due to KPC-producing K. pneumoniae are limited, and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates. Methods Using clinically-relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime-avibactam, meropenem, rifampin, and amikacin alone and in combination. Four isolates of KPC-producing K. pneumoniae were studied, including two isolates that were resistant to polymyxin B and had ceftazidime-avibactam MICs of 8 µg/mL. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower MICs of ceftazidime-avibactam. Results Two isolates that were resistant to polymyxin B and with ceftazidime-avibactam MICs of 8 µg/mL were also resistant to amikacin and meropenem. When ceftazidime-avibactam was combined with either amikacin or meropenem, synergy was observed in vitro, and these combinations were associated with improved survival with the in vivo model. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower MICs of ceftazidime-avibactam. At concentrations four times the MIC, ceftazidime-avibactam had bactericidal activity in vitro; at one fourth the MIC, synergy was observed when combined with meropenem. Improved survival rates were observed with therapy with ceftazidime-avibactam, particularly when combined with a second agent for one isolate. In the in vivo model, polymyxin B with or without rifampin or meropenem, was ineffective against polymyxin B resistant strains. Conclusion Pending clinical studies, combining ceftazidime-avibactam with another agent (e.g., a carbapenem) should be encouraged when treating serious infections due to these pathogens, especially for isolates with ceftazidime-avibactam MICs near the susceptibility breakpoint. Disclosures All authors: No reported disclosures.

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