Antibiotics as Tool to Investigate Cell Functional State

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 13858

Special Issue Editors


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Guest Editor
Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy
Interests: polyene antibiotics; bioactive molecules; clinical applications and diagnosis

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Guest Editor
Department of Psychology, Division of Neuroscience and "Daniel Bovet" Neurobiology Research Center, Sapienza University of Rome, Roma, Italy
Interests: cerebellar development; cerebellar granule neurons; neurodegeneration; cholesterol dyshomeostasis

Special Issue Information

Dear Colleagues,

In recent years, the use of antibiotics beyond their canonical antibacterial role has come to represent a field with a wide range of applications.

Antibiotics have been studied as a tool to overcome drug resistance in cancer cells, modulate enzymatic and inflammatory responses, mark cell function in pathologies related to changes in protein or lipid profile, and regulate cell redox homeostasis in some pathophysiological conditions.

For example, myriocin is employed in biochemical research to deplete sphingolipids by inhibiting the de novo synthesis of ceramide, whereas filipin, as a naturally fluorescent polyene antibiotic that selectively binds to cholesterol, is commonly used as an accurate histochemical marker for the diagnosis of disorders that lead to the accumulation of cholesterol in lysosomal organelles. Furthermore, some naturally occurring antibiotics have been studied as a subgroup of small signaling molecules that influence the gene expression of many cellular functions.

This Special Issue focuses on the structural and functional aspects of the alternative use of antibiotics and on the continuous progress performed in antibiotic research in the fields of genetics, molecular biology and synthesis by biocatalysis, as well as biotechnological and biomedical applications.

Dr. Elisabetta Capuozzo
Dr. Sonia Canterini 
Guest Editors 

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Keywords

  • polyene antibiotics
  • molecular biomarkers
  • inflammation
  • immune system
  • neurological disorders
  • cancer
  • clinical applications and diagnosis
  • biocatalysis
  • bioactive molecules
  • impact of new antibiotics on human health and diseases

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Published Papers (4 papers)

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Research

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20 pages, 7009 KiB  
Article
The Triprenylated Anthranoid Ferruginin A, a Promising Scaffold for the Development of Novel Antibiotics against Gram-Positive Bacteria
by Bruno Casciaro, Francesca Ghirga, Floriana Cappiello, Valeria Vergine, Maria Rosa Loffredo, Silvia Cammarone, Elena Puglisi, Carola Tortora, Deborah Quaglio, Mattia Mori, Bruno Botta and Maria Luisa Mangoni
Antibiotics 2022, 11(1), 84; https://doi.org/10.3390/antibiotics11010084 - 11 Jan 2022
Cited by 1 | Viewed by 2104
Abstract
In today’s post-antibiotic era, the search for new antimicrobial compounds is of major importance and nature represents one of the primary sources of bioactive molecules. In this work, through a cheminformatics approach, we clustered an in-house library of natural products and their derivatives [...] Read more.
In today’s post-antibiotic era, the search for new antimicrobial compounds is of major importance and nature represents one of the primary sources of bioactive molecules. In this work, through a cheminformatics approach, we clustered an in-house library of natural products and their derivatives based on a combination of fingerprints and substructure search. We identified the prenylated emodine-type anthranoid ferruginin A as a novel antimicrobial compound. We tested its ability to inhibit and kill a panel of Gram-positive and Gram-negative bacteria, and compared its activity with that of two analogues, vismione B and ferruanthrone. Furthermore, the capability of these three anthranoids to disrupt staphylococcal biofilm was investigated, as well as their effect on the viability of human keratinocytes. Ferruginin A showed a potent activity against both the planktonic and biofilm forms of Gram-positive bacteria (i.e., Staphylococcus aureus and S. epidermidis) and had the best therapeutic index compared to vismione B and ferruanthrone. In conclusion, ferruginin A represents a promising scaffold for the further development of valuable antimicrobial agents. Full article
(This article belongs to the Special Issue Antibiotics as Tool to Investigate Cell Functional State)
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Review

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12 pages, 877 KiB  
Review
The Antifungal Antibiotic Filipin as a Diagnostic Tool of Cholesterol Alterations in Lysosomal Storage Diseases and Neurodegenerative Disorders
by Francesco Bruno, Serena Camuso, Elisabetta Capuozzo and Sonia Canterini
Antibiotics 2023, 12(1), 122; https://doi.org/10.3390/antibiotics12010122 - 9 Jan 2023
Cited by 4 | Viewed by 2753
Abstract
Cholesterol is the most considerable member of a family of polycyclic compounds understood as sterols, and represents an amphipathic molecule, such as phospholipids, with the polar hydroxyl group located in position 3 and the rest of the molecule is completely hydrophobic. In cells, [...] Read more.
Cholesterol is the most considerable member of a family of polycyclic compounds understood as sterols, and represents an amphipathic molecule, such as phospholipids, with the polar hydroxyl group located in position 3 and the rest of the molecule is completely hydrophobic. In cells, it is usually present as free, unesterified cholesterol, or as esterified cholesterol, in which the hydroxyl group binds to a carboxylic acid and thus generates an apolar molecule. Filipin is a naturally fluorescent antibiotic that exerts a primary antifungal effect with low antibacterial activity, interfering with the sterol stabilization of the phospholipid layers and favoring membrane leakage. This polyene macrolide antibiotic does not bind to esterified sterols, but only to non-esterified cholesterol, and it is commonly used as a marker to label and quantify free cholesterol in cells and tissues. Several lines of evidence have indicated that filipin staining could be a good diagnostic tool for the cholesterol alterations present in neurodegenerative (e.g., Alzheimer’s Disease and Huntington Disease) and lysosomal storage diseases (e.g., Niemann Pick type C Disease and GM1 gangliosidosis). Here, we have discussed the uses and applications of this fluorescent molecule in lipid storage diseases and neurodegenerative disorders, exploring not only the diagnostic strength of filipin staining, but also its limitations, which over the years have led to the development of new diagnostic tools to combine with filipin approach. Full article
(This article belongs to the Special Issue Antibiotics as Tool to Investigate Cell Functional State)
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23 pages, 751 KiB  
Review
Exposure to Antibiotics and Neurodevelopmental Disorders: Could Probiotics Modulate the Gut–Brain Axis?
by Tamara Diamanti, Roberta Prete, Natalia Battista, Aldo Corsetti and Antonella De Jaco
Antibiotics 2022, 11(12), 1767; https://doi.org/10.3390/antibiotics11121767 - 7 Dec 2022
Cited by 11 | Viewed by 4123
Abstract
In order to develop properly, the brain requires the intricate interconnection of genetic factors and pre-and postnatal environmental events. The gut–brain axis has recently raised considerable interest for its involvement in regulating the development and functioning of the brain. Consequently, alterations in the [...] Read more.
In order to develop properly, the brain requires the intricate interconnection of genetic factors and pre-and postnatal environmental events. The gut–brain axis has recently raised considerable interest for its involvement in regulating the development and functioning of the brain. Consequently, alterations in the gut microbiota composition, due to antibiotic administration, could favor the onset of neurodevelopmental disorders. Literature data suggest that the modulation of gut microbiota is often altered in individuals affected by neurodevelopmental disorders. It has been shown in animal studies that metabolites released by an imbalanced gut–brain axis, leads to alterations in brain function and deficits in social behavior. Here, we report the potential effects of antibiotic administration, before and after birth, in relation to the risk of developing neurodevelopmental disorders. We also review the potential role of probiotics in treating gastrointestinal disorders associated with gut dysbiosis after antibiotic administration, and their possible effect in ameliorating neurodevelopmental disorder symptoms. Full article
(This article belongs to the Special Issue Antibiotics as Tool to Investigate Cell Functional State)
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14 pages, 979 KiB  
Review
Antimicrobial Peptides (AMPs) in the Pathogenesis of Alzheimer’s Disease: Implications for Diagnosis and Treatment
by Francesco Bruno, Antonio Malvaso, Sonia Canterini and Amalia Cecilia Bruni
Antibiotics 2022, 11(6), 726; https://doi.org/10.3390/antibiotics11060726 - 28 May 2022
Cited by 25 | Viewed by 3784
Abstract
Alzheimer’s disease (AD) represents the most frequent type of dementia in elderly people. There are two major forms of the disease: sporadic (SAD)—whose causes are not completely understood—and familial (FAD)—with clear autosomal dominant inheritance. The two main hallmarks of AD are extracellular deposits [...] Read more.
Alzheimer’s disease (AD) represents the most frequent type of dementia in elderly people. There are two major forms of the disease: sporadic (SAD)—whose causes are not completely understood—and familial (FAD)—with clear autosomal dominant inheritance. The two main hallmarks of AD are extracellular deposits of amyloid-beta (Aβ) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein (P-tau). An ever-growing body of research supports the infectious hypothesis of sporadic forms of AD. Indeed, it has been documented that some pathogens, such as herpesviruses and certain bacterial species, are commonly present in AD patients, prompting recent clinical research to focus on the characterization of antimicrobial peptides (AMPs) in this pathology. The literature also demonstrates that Aβ can be considered itself as an AMP; thus, representing a type of innate immune defense peptide that protects the host against a variety of pathogens. Beyond Aβ, other proteins with antimicrobial activity, such as lactoferrin, defensins, cystatins, thymosin β4, LL37, histatin 1, and statherin have been shown to be involved in AD. Here, we summarized and discussed these findings and explored the diagnostic and therapeutic potential of AMPs in AD. Full article
(This article belongs to the Special Issue Antibiotics as Tool to Investigate Cell Functional State)
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