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Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities.

Cushnie, T.P. Tim; Cushnie, Benjamart; Lamb, Andrew J.

Authors

T.P. Tim Cushnie

Benjamart Cushnie

Andrew J. Lamb



Abstract

With reports of pandrug-resistant bacteria causing untreatable infections, the need for new antibacterial therapies is more pressing than ever. Alkaloids are a large and structurally diverse group of compounds that have served as scaffolds for important antibacterial drugs such as metronidazole and the quinolones. In this review, we highlight other alkaloids with development potential. Natural, semisynthetic and synthetic alkaloids of all classes are considered, looking first at those with direct antibacterial activity and those with antibiotic-enhancing activity. Potent examples include CJ-13,136, a novel actinomycete-derived quinolone alkaloid with a minimum inhibitory concentration of 0.1 ng/mL against Helicobacter pylori, and squalamine, a polyamine alkaloid from the dogfish shark that renders Gram-negative pathogens 16- to >32-fold more susceptible to ciprofloxacin. Where available, information on toxicity, structure-activity relationships, mechanisms of action and in vivo activity is presented. The effects of alkaloids on virulence gene regulatory systems such as quorum sensing and virulence factors such as sortases, adhesins and secretion systems are also described. The synthetic isoquinoline alkaloid virstatin, for example, inhibits the transcriptional regulator ToxT in Vibrio cholerae, preventing expression of cholera toxin and fimbriae and conferring in vivo protection against intestinal colonisation. The review concludes with implications and limitations of the described research and directions for future research.

Citation

CUSHNIE, T.P.T., CUSHNIE, B. and LAMB, A.J. 2014. Alkaloids: an overview of their antibacterial, anibiotic-enhancing and antivirulence activities. International journal of antimicrobial agents [online], 44(5), pages 377-386. Available from: https://doi.org/10.1016/j.ijantimicag.2014.06.001

Journal Article Type Review
Acceptance Date Jun 20, 2014
Online Publication Date Jul 15, 2014
Publication Date Nov 30, 2014
Deposit Date Feb 19, 2021
Publicly Available Date Sep 5, 2022
Journal International Journal of Antimicrobial Agents
Print ISSN 0924-8579
Electronic ISSN 1872-7913
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 44
Issue 5
Pages 377-386
DOI https://doi.org/10.1016/j.ijantimicag.2014.06.001
Keywords Alkaloid; Antibacterial; Structure–activity; Mechanism of action; Synergy; Antivirulence
Public URL https://rgu-repository.worktribe.com/output/1168236
Additional Information This article has been published with separate supporting information. This supporting information has been incorporated into a single file on this repository and can be found at the end of this document.

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