scholarly journals Anti-Infective Antibody-Derived Peptides Active against Endogenous and Exogenous Fungi

2021 ◽  
Vol 9 (1) ◽  
pp. 143
Author(s):  
Tecla Ciociola ◽  
Laura Giovati ◽  
Stefania Conti ◽  
Walter Magliani

Mycoses still represent relevant opportunistic infections worldwide, although overshadowed in recent years by other severe and more widespread infections. Moreover, deep-seated mycoses are often accompanied by unacceptably high mortality rates. Etiologic agents include endogenous components of the mycobiota, Candida and Malassezia species above all, and exogenous species, both yeasts and filamentous fungi. Old and new fungal pathogens are increasingly characterized by resistance to the existing antifungal agents, making imperative the search for effective and safe new therapeutics. Among the candidate molecules proposed in recent decades, synthetic peptides derived from the complementarity determining and constant regions of diverse antibodies (Abs), as well as the translated products of Ab-encoding genes, have proved of considerable interest. Their anti-infective activities, regardless of the specificity and isotype of the originating Ab, will be briefly presented and discussed in the light of their different mechanisms of action. Intriguing suggestions on the possible function of Abs after their half-life will be presented, following the recent detection, in human serum, of an antimicrobial Ab-derived peptide. Overall, Abs could represent a source of biologically active, highly flexible peptides, devoid of detectable toxicity, which can be easily synthesized and manipulated to be used, alone or in association with already available drugs, for new anti-infective strategies.

1999 ◽  
Vol 12 (1) ◽  
pp. 40-79 ◽  
Author(s):  
Daniel J. Sheehan ◽  
Christopher A. Hitchcock ◽  
Carol M. Sibley

SUMMARY Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided.


1991 ◽  
Vol 53 (1) ◽  
pp. 144-151 ◽  
Author(s):  
Mamoru YOKOO ◽  
Tadashi ARIKA ◽  
Yoshiro SOH

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 984
Author(s):  
Rima El-Dirany ◽  
Hawraa Shahrour ◽  
Zeinab Dirany ◽  
Fadi Abdel-Sater ◽  
Gustavo Gonzalez-Gaitano ◽  
...  

Anti-microbial peptides (AMPs), small biologically active molecules, produced by different organisms through their innate immune system, have become a considerable subject of interest in the request of novel therapeutics. Most of these peptides are cationic-amphipathic, exhibiting two main mechanisms of action, direct lysis and by modulating the immunity. The most commonly reported activity of AMPs is their anti-bacterial effects, although other effects, such as anti-fungal, anti-viral, and anti-parasitic, as well as anti-tumor mechanisms of action have also been described. Their anti-parasitic effect against leishmaniasis has been studied. Leishmaniasis is a neglected tropical disease. Currently among parasitic diseases, it is the second most threating illness after malaria. Clinical treatments, mainly antimonial derivatives, are related to drug resistance and some undesirable effects. Therefore, the development of new therapeutic agents has become a priority, and AMPs constitute a promising alternative. In this work, we describe the principal families of AMPs (melittin, cecropin, cathelicidin, defensin, magainin, temporin, dermaseptin, eumenitin, and histatin) exhibiting a potential anti-leishmanial activity, as well as their effectiveness against other microorganisms.


Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1109
Author(s):  
Cristina Adriana Dehelean ◽  
Iasmina Marcovici ◽  
Codruta Soica ◽  
Marius Mioc ◽  
Dorina Coricovac ◽  
...  

Despite the recent advances in the field of chemically synthetized pharmaceutical agents, nature remains the main supplier of bioactive molecules. The research of natural products is a valuable approach for the discovery and development of novel biologically active compounds possessing unique structures and mechanisms of action. Although their use belongs to the traditional treatment regimes, plant-derived compounds still cover a large portion of the current-day pharmaceutical agents. Their medical importance is well recognized in the field of oncology, especially as an alternative to the limitations of conventional chemotherapy (severe side effects and inefficacy due to the occurrence of multi-drug resistance). This review offers a comprehensive perspective of the first blockbuster chemotherapeutic agents of natural origin’s (e.g. taxol, vincristine, doxorubicin) mechanism of action using 3D representation. In addition is portrayed the step-by-step evolution from preclinical to clinical evaluation of the most recently studied natural compounds with potent antitumor activity (e.g. resveratrol, curcumin, betulinic acid, etc.) in terms of anticancer mechanisms of action and the possible indications as chemotherapeutic or chemopreventive agents and sensitizers. Finally, this review describes several efficient platforms for the encapsulation and targeted delivery of natural compounds in cancer treatment


1995 ◽  
Vol 109 (12) ◽  
pp. 1197-1199 ◽  
Author(s):  
R. B. S. Laing ◽  
P. J. C. Wardrop ◽  
P. D. Welsby ◽  
R. P. Brettle

AbstractThe immunodeficiency which results from HIV infection is associated with a range of opportunistic infections and tumours which may present with the symptoms of upper airways disease. This paper presents three cases of stridor from different causes in patients with HIV infection, all of whom recovered following treatment. The management of this problem requires consideration of the likely aetiology which, in those with advanced immunodeficiency, includes bacterial and fungal laryngitis and epiglottitis as well as rapidly growing laryngeal tumours. Recommendations for the treatment of those with HIV infection who present with severe or rapidonset stridor should include a combination of aggressive airway intervention and broad-spectrum antibacterial and antifungal agents. Laryngeal biopsy for histology and culture is particularly important for those patients who fail to respond to the aforementioned treatment.


Author(s):  
L. L. Zakharova ◽  
◽  
G. A. Zhorov ◽  
V. N. Obryvin ◽  
◽  
...  

The article presents the results of laboratory studies of the effect of sorption-detoxifying means on the accumulation of 90Sr in the body of white rats. The efficiency of a number of selective and polyfunctional sorbents, detoxicants and other biologically active substances and the developed on their basis sorption-detoxifying complexes as means of efferent therapy and detoxification of the animal body at the combined intake of xenobiotics of radiation and chemical nature was evaluated. It was found that 90Sr cumulation in bones (at the level of 53,3–60,8%) was reduced to the greatest extent with the combined use of substances of different mechanisms of action and origin. The effectiveness of separate use of detoxifying drugs did not exceed 29,1%.


2009 ◽  
Vol 16 (10) ◽  
pp. 1527-1528 ◽  
Author(s):  
Rafael Zaragoza ◽  
Javier Pemán ◽  
Guillermo Quindós ◽  
Jose R. Iruretagoyena ◽  
María S. Cuétara ◽  
...  

ABSTRACT The influence of kinetic patterns of Candida albicans germ tube antibodies (CAGTA) on mortality was analyzed in six intensive care units. Statistically significant lower mortality rates were found in patients with patterns of increasing CAGTA titers who had been treated with antifungal agents. Thus, antifungal treatment should be considered when CAGTA titers are increasing in critically ill patients.


ChemInform ◽  
2010 ◽  
Vol 31 (6) ◽  
pp. no-no
Author(s):  
Seth Y. Ablordeppey ◽  
Pingchen Fan ◽  
Joy H. Ablordeppey ◽  
Leroy Mardenborough

2002 ◽  
Vol 46 (4) ◽  
pp. 947-957 ◽  
Author(s):  
N. Jia ◽  
B. Arthington-Skaggs ◽  
W. Lee ◽  
C. A. Pierson ◽  
N. D. Lees ◽  
...  

ABSTRACT The incidence of fungal infections has increased dramatically, which has necessitated additional and prolonged use of the available antifungal agents. Increased resistance to the commonly used antifungal agents, primarily the azoles, has been reported, thus necessitating the discovery and development of compounds that would be effective against the major human fungal pathogens. The sterol biosynthetic pathway has proved to be a fertile area for antifungal development, and steps which might provide good targets for novel antifungal development remain. The sterol C-14 reductase, encoded by the ERG24 gene, could be an effective target for drug development since the morpholine antifungals, inhibitors of Erg24p, have been successful in agricultural applications. The ERG24 gene of Candida albicans has been isolated by complementation of a Saccharomyces cerevisiae erg24 mutant. Both copies of the C. albicans ERG24 gene have been disrupted by using short homologous regions of the ERG24 gene flanking a selectable marker. Unlike S. cerevisiae, the C. albicans ERG24 gene was not required for growth, but erg24 mutants showed several altered phenotypes. They were demonstrated to be slowly growing, with doubling times at least twice that of the wild type. They were also shown to be significantly more sensitive to an allylamine antifungal and to selected cellular inhibitors including cycloheximide, cerulenin, fluphenazine, and brefeldin A. The erg24 mutants were also slightly resistant to the azoles. Most importantly, erg24 mutants were shown to be significantly less pathogenic in a mouse model system and failed to produce germ tubes upon incubation in human serum. On the basis of these characteristics, inhibitors of Erg24p would be effective against C. albicans.


2019 ◽  
Vol 57 (Supplement_3) ◽  
pp. S307-S317 ◽  
Author(s):  
Christopher P Eades ◽  
Darius P H Armstrong-James

AbstractThe use of cytotoxic chemotherapy in the treatment of malignant and inflammatory disorders is beset by considerable adverse effects related to nonspecific cytotoxicity. Accordingly, a mechanistic approach to therapeutics has evolved in recent times with small molecular inhibitors of intracellular signaling pathways involved in disease pathogenesis being developed for clinical use, some with unparalleled efficacy and tolerability. Nevertheless, there are emerging concerns regarding an association with certain small molecular inhibitors and opportunistic infections, including invasive fungal diseases. This is perhaps unsurprising, given that the molecular targets of such agents play fundamental and multifaceted roles in orchestrating innate and adaptive immune responses. Nevertheless, some small molecular inhibitors appear to possess intrinsic antifungal activity and may therefore represent novel therapeutic options in future. This is particularly important given that antifungal resistance is a significant, emerging concern. This paper is a comprehensive review of the state-of-the-art in the molecular immunology to fungal pathogens as applied to existing and emerging small molecular inhibitors.


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