Targeting Bacterial Sortases in Search of Anti-Virulence Therapies with Low Risk of Resistance Development

Increasingly ineffective antibiotics and rapid spread of multi- and pan-resistant bacteria represent a global health threat; hence, the need of developing new antimicrobial medicines. A first step in this direction is identifying new molecular targets, such as virulence factors. Sortase A represents...

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Bibliographic Details
Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2021-04, Vol.14 (5), p.415
Main Authors: Nitulescu, Georgiana, Margina, Denisa, Zanfirescu, Anca, Olaru, Octavian Tudorel, Nitulescu, George Mihai
Format: Article
Language:English
Subjects:
Bacteria
Biofilms
covalent inhibitors
Drug resistance
E coli
Enzymes
flavonoids
Gram-positive bacteria
Gram-positive pathogens
Immune system
Pathogens
Peptides
Proteins
Review
sortase A inhibitors
Staphylococcus aureus
Staphylococcus infections
Streptococcus infections
Streptococcus mutans
Virulence
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Summary:Increasingly ineffective antibiotics and rapid spread of multi- and pan-resistant bacteria represent a global health threat; hence, the need of developing new antimicrobial medicines. A first step in this direction is identifying new molecular targets, such as virulence factors. Sortase A represents a virulence factor essential for the pathogenesis of Gram-positive pathogens, some of which have a high risk for human health. We present here an exhaustive collection of sortases inhibitors grouped by relevant chemical features: vinyl sulfones, 3-aryl acrylic acids and derivatives, flavonoids, naphtoquinones, anthraquinones, indoles, pyrrolomycins, isoquinoline derivatives, aryl β-aminoethyl ketones, pyrazolethiones, pyridazinones, benzisothiazolinones, 2-phenyl-benzoxazole and 2-phenyl-benzofuran derivatives, thiadiazoles, triazolothiadiazoles, 2-(2-phenylhydrazinylidene)alkanoic acids, and 1,2,4-thiadiazolidine-3,5-dione. This review focuses on highlighting their structure-activity relationships, using the half maximal inhibitory concentration (IC ), when available, as an indicator of each compound effect on a specific sortase. The information herein is useful for acquiring knowledge on diverse natural and synthetic sortases inhibitors scaffolds and for understanding the way their structural variations impact IC . It will hopefully be the inspiration for designing novel effective and safe sortase inhibitors in order to create new anti-infective compounds and to help overcoming the current worldwide antibiotic shortage.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph14050415