scholarly journals Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model

2018 ◽  
Vol 73 (8) ◽  
pp. 2085-2088 ◽  
Author(s):  
Christopher L Hager ◽  
Emily L Larkin ◽  
Lisa A Long ◽  
Mahmoud A Ghannoum
Keyword(s):  
Mouse Model ◽  
Candida Auris ◽  
Immunocompromised Mouse

An immunocompromised mouse model to infect Ixodes scapularis ticks with the relapsing fever spirochete, Borrelia miyamotoi

2019 ◽  
Vol 10 (2) ◽  
pp. 352-359 ◽  
Author(s):  
Geoffrey E. Lynn ◽  
Nicole E. Breuner ◽  
Lars Eisen ◽  
Andrias Hojgaard ◽  
Adam J. Replogle ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ixodes Scapularis ◽  
Borrelia Miyamotoi ◽  
Relapsing Fever ◽  
Immunocompromised Mouse

scholarly journals Role of Ethanolamine Utilization Genes in Host Colonization during Urinary Tract Infection

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Anna Sintsova ◽  
Sara Smith ◽  
Sargurunathan Subashchandrabose ◽  
Harry L. Mobley
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Mouse Model ◽  
Virulence Determinants ◽  
Content Type ◽  
Immunocompromised Mouse ◽  
Common Infection ◽  
Increased Susceptibility

ABSTRACTUrinary tract infection (UTI) is the second most common infection in humans, making it a global health priority. Nearly half of all women will experience a symptomatic UTI, with uropathogenicEscherichia coli(UPEC) being the major causative agent of the infection. Although there has been extensive research on UPEC virulence determinants, the importance of host-specific metabolism remains understudied. We report here that UPEC upregulates the expression of ethanolamine utilization genes during uncomplicated UTIs in humans. We further show that UPEC ethanolamine metabolism is required for effective bladder colonization in the mouse model of ascending UTI and is dispensable for bladder colonization in an immunocompromised mouse model of UTI. We demonstrate that although ethanolamine metabolism mutants do not show increased susceptibility to antimicrobial responses of neutrophils, this metabolic pathway is important for surviving the innate immune system during UTI. This study reveals a novel aspect of UPEC metabolism in the host and provides evidence for an underappreciated link between bacterial metabolism and the host immune response.

scholarly journals A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease

2012 ◽  
Vol 18 (12) ◽  
pp. 1820-1826 ◽  
Author(s):  
Rachel L Graham ◽  
Michelle M Becker ◽  
Lance D Eckerle ◽  
Meagan Bolles ◽  
Mark R Denison ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immunocompromised Mouse

scholarly journals In vitro and in vivo interaction of caspofungin with isavuconazole against Candida auris planktonic cells and biofilms

2021 ◽  
Author(s):  
Fruzsina Nagy ◽  
Zoltán Tóth ◽  
Fanni Nyikos ◽  
Lajos Forgács ◽  
Ágnes Jakab ◽  
...  
Keyword(s):  
Favourable Effect ◽  
Planktonic Cells ◽  
Candida Auris ◽  
Synergistic Interactions ◽  
Immunocompromised Mouse ◽  
Concentration Indices ◽  
Volume Range ◽  
Bliss Independence

AbstractThe in vitro and in vivo efficacy of caspofungin was determined in combination with isavuconazole against Candida auris. Drug–drug interactions were assessed utilising the fractional inhibitory concentration indices (FICIs), the Bliss independence model and an immunocompromised mouse model. Median planktonic minimum inhibitory concentrations (pMICs) of 23 C. auris isolates were between 0.5 and 2 mg/L and between 0.015 and 4 mg/L for caspofungin and isavuconazole, respectively. Median pMICs for caspofungin and isavuconazole in combination showed 2–128-fold and 2–256-fold decreases, respectively. Caspofungin and isavuconazole showed synergism in 14 out of 23 planktonic isolates (FICI range 0.03–0.5; Bliss cumulative synergy volume range 0–4.83). Median sessile MICs (sMIC) of 14 biofilm-forming isolates were between 32 and >32 mg/L and between 0.5 and >2 mg/L for caspofungin and isavuconazole, respectively. Median sMICs for caspofungin and isavuconazole in combination showed 0–128-fold and 0-512-fold decreases, respectively. Caspofungin and isavuconazole showed synergistic interaction in 12 out of 14 sessile isolates (FICI range 0.023–0.5; Bliss cumulative synergy volume range 0.13–234.32). In line with the in vitro findings, synergistic interactions were confirmed by in vivo experiments. The fungal kidney burden decreases were more than 3 log volumes in mice treated with combination of 1 mg/kg caspofungin and 20 mg/kg isavuconazole daily; this difference was statistically significant compared with control mice (p<0.001). Despite the favourable effect of isavuconazole in combination with caspofungin, further studies are needed to confirm the therapeutic advantage of this combination when treating an infection caused by C. auris.

scholarly journals The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Hai-Jun Hu ◽  
Xiu Liang ◽  
Hai-Lang Li ◽  
Chun-Ming Du ◽  
Jia-Li Hao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tumor Cells ◽  
Antitumor Immunity ◽  
Oncolytic Adenovirus ◽  
The Self ◽  
Indirect Pathway ◽  
Immunocompetent Mouse ◽  
Tumor Cell Death ◽  
Immunocompromised Mouse ◽  
Direct Killing

AbstractZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a “nonself” label in tumor cells and then turn the tumor cells from the “self” state into the “nonself” state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.

scholarly journals Optimizing T-705 (favipiravir) treatment of severe influenza B virus infection in the immunocompromised mouse model

2019 ◽  
Vol 74 (5) ◽  
pp. 1333-1341 ◽  
Author(s):  
Philippe Noriel Q Pascua ◽  
Bindumadhav M Marathe ◽  
Peter Vogel ◽  
Richard J Webby ◽  
Elena A Govorkova
Keyword(s):  
Virus Infection ◽  
Mouse Model ◽  
Influenza B Virus ◽  
Influenza B ◽  
Severe Influenza ◽  
Immunocompromised Mouse ◽  
B Virus

Impact of FKS 1 genotype on echinocandin in-vitro susceptibility in Candida auris and in -vivo response in a murine model of infection

2021 ◽  
Author(s):  
Dipti Sharma ◽  
Raees A. Paul ◽  
Shivaprakash M. Rudramurthy ◽  
Nisha Kashyap ◽  
Sanjay Bhattacharya ◽  
...  
Keyword(s):  
Mouse Model ◽  
Murine Model ◽  
Resistance Mechanism ◽  
Wild Type ◽  
Candida Auris ◽  
In Vitro Susceptibility ◽  
Chitin Content ◽  
Echinocandin Resistance

Objectives: Echinocandins are frontline antifungal agents in the management of invasive infections due to multi-drug resistant Candida auris . The study aimed to evaluate echinocandin resistance in C. auris isolates of multicentric origin, identify the resistance mechanism, and analyze the pharmacodynamic response to caspofungin in a neutropenic mouse model of infection. Methods : A total of 199 C. auris isolates originating from thirty centres across India were tested for susceptibility to echinocandins. Isolates with reduced susceptibility were evaluated for FKS 1 mutations and in-vivo response to caspofungin in a murine model of disseminated candidiasis. In addition, the response to echinocandins was assessed in light of in-vitro growth kinetics, chitin content; and transcript levels of chitin synthase and FKS1 genes. Results: We report 10 resistant C. auris isolates with four FKS 1 mutations: F635Y ( n =2), F635L ( n =4), S639F ( n =3), and R1354S ( n =1). Of these, F635Y and R1354S exhibited the most profound resistance in mouse model of disseminated infection. S639F and F635L mutations conferred a moderate in vivo resistance, whereas wild-type isolates exhibiting borderline MIC were susceptible in vivo . FKS 1 genotype was more accurate predictor of in-vivo response than the MIC of the isolates. Isolates with high basal or inducible chitin content exhibited higher in vitro MIC in FKS 1 mutant compared to wild-type. Conclusions FKS 1 mutations play a major role in clinically relevant echinocandin resistance in C. auris with differential in vivo outcomes. This study could have implications for clinical practice and, therefore, warrants further studies.

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