Therapy of murine pulmonary aspergillosis with antibody-alliinase conjugates and alliin.

Antimicrobial Agents and Chemotherapy
Elena AppelDavid Mirelman

Abstract

Aspergillus fumigatus is an opportunistic fungal pathogen responsible for invasive aspergillosis in immunocompromised individuals. The high morbidity and mortality rates as well as the poor efficacy of antifungal agents remain major clinical concerns. Allicin (diallyl-dithiosulfinate), which is produced by the garlic enzyme alliinase from the harmless substrate alliin, has been shown to have wide-range antifungal specificity. A monoclonal antibody (MAb) against A. fumigatus was produced and chemically ligated to the enzyme alliinase. The purified antibody-alliinase conjugate bound to conidia and hyphae of A. fumigatus at nanomolar concentrations. In the presence of alliin, the conjugate produced cytotoxic allicin molecules, which killed the fungus. In vivo testing of the therapeutical potential of the conjugate was carried out in immunosuppressed mice infected intranasally with conidia of A. fumigatus. Intratracheal (i.t.) instillation of the conjugate and alliin (four treatments) resulted in 80 to 85% animal survival (36 days), with almost complete fungal clearance. Repetitive intratracheal administration of the conjugate and alliin was also effective when treatments were initiated at a more advanced stage of infection (50 h)....Continue Reading

References

Sep 1, 1978·Clinical Allergy·J Mullins, A Seaton
Jan 1, 1973·Oncology·W Ho, A Furst
Dec 1, 1983·Infection and Immunity·A SchaffnerC E Davis
Sep 1, 1994·Applied Biochemistry and Biotechnology·A RabinkovD Mirelman
Aug 1, 1996·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·C Darras-JolyJ P Bédos
Dec 14, 1999·Microbes and Infection·S Ankri, D Mirelman
Apr 26, 2000·Clinical Immunology : the Official Journal of the Clinical Immunology Society·M PietropaoloM P Happ
Aug 22, 2001·Trends in Microbiology·J P Latgé
Jan 5, 2002·Applied Microbiology and Biotechnology·J C HarrisD Lloyd
Jul 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Linda J W ShimonFelix Frolow
Jul 30, 2002·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Raleigh BowdenJohn R Wingard
Jan 24, 2003·Infection and Immunity·O Ibrahim-GranetJ P Latgé
Mar 18, 2003·Journal of Cell Science·Julie A Wasylnka, Margo M Moore
Jun 25, 2003·Antimicrobial Agents and Chemotherapy·Ruth C MatthewsJames Burnie
Sep 17, 2003·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·William J Steinbach, David A Stevens
Dec 5, 2003·Lancet·Michail S Lionakis, Dimitrios P Kontoyiannis
Jan 18, 2005·Clinical Microbiology Reviews·Nina Singh, David L Paterson
May 27, 2005·British Journal of Haematology·Shmuel Shoham, Stuart M Levitz
Feb 28, 2006·Analytical Biochemistry·T MironM Wilchek
Jun 15, 2006·Journal of Medical Microbiology·D A EnochN M Brown
Oct 31, 2006·Expert Review of Anticancer Therapy·Kenneth D Bagshawe
May 28, 2008·Mycoses·W J Heinz, H Einsele
Jul 9, 2008·Antimicrobial Agents and Chemotherapy·Alexandra Vallon-EberhardYechiel Shai
Jan 31, 2009·Medical Mycology·Luigina Romani
Mar 18, 2009·Antimicrobial Agents and Chemotherapy·Justin A TolmanRobert O Williams
Jul 23, 2009·Expert Review of Anti-infective Therapy·Emilia CantónJavier Pemán

❮ Previous
Next ❯

Citations

Aug 4, 2010·Journal of Drug Targeting·Elena AppelDavid Mirelman
Nov 19, 2014·Seminars in Immunopathology·Sri Ramulu ElluruJagadeesh Bayry
Feb 9, 2020·Journal of Fungi·Sebastian Ulrich, Frank Ebel
Mar 4, 2020·Journal of Fungi·Camila BonicheCarlos Pelleschi Taborda
Mar 25, 2016·The Journal of Biological Chemistry·Alexandra MüllerLars Ingo Ole Leichert

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Aspergillosis

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Aspergillosis (ASM)

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.