Article: Repurposing drugs with specific activity against L-form bacteria.
2023 Volume 14, Page(s) 1097413
Abstract: Cell wall deficient "L- form" bacteria are of growing medical interest as a possible source of recurrent or persistent infection, largely because of their complete resistance to cell wall active antibiotics such as β-lactams. Antibiotics that ... ...
Abstract | Cell wall deficient "L- form" bacteria are of growing medical interest as a possible source of recurrent or persistent infection, largely because of their complete resistance to cell wall active antibiotics such as β-lactams. Antibiotics that specifically kill L-forms would be of potential interest as therapeutics, but also as reagents with which to explore the role of L-forms in models of recurrent infection. To look for specific anti-L-form antibiotics, we screened a library of several hundred FDA-approved drugs and identified compounds highly selective for L-form killing. Among the compounds identified were representatives of two different classes of calcium channel blockers: dihydropyridines, e.g., manidipine; and diphenylmethylpiperazine, e.g., flunarizine. Mode of action studies suggested that both classes of compound work by decreasing membrane fluidity. This leads to a previously recognized phenotype of L-forms in which the cells can continue to enlarge but fail to divide. We identified a considerable degree of variation in the activity of different representatives of the two classes of compounds, suggesting that it may be possible to modify them for use as drugs for L-form-dependent infections. |
---|---|
Language | English |
Publishing date | 2023-04-04 |
Publishing country | Switzerland |
Document type | Journal Article |
ZDB-ID | 2587354-4 |
ISSN | 1664-302X |
ISSN | 1664-302X |
DOI | 10.3389/fmicb.2023.1097413 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.