Computational identification of a systemic antibiotic for Gram-negative bacteria

Miller, Ryan D.; Iinishi, Akira; Modaresi, Seyed Majed; Yoo, Byung‐Kuk; Curtis, Thomas D.; Lariviere, Patrick J.; Liang, Libang; Son, Sangkeun; Nicolau, Samantha E.; Bargabos, Rachel; Morrissette, Madeleine; Gates, Michael F.; Pitt, Norman; Jakob, R.P.; Rath, Parthasarathi; Maier, Timm; Malyutin, Andrey; Kaiser, Jens T.; Niles, Samantha; Karavas, Blake; Ghiglieri, Meghan; Bowman, Sarah; Rees, Douglas C.; Hiller, Sebastian; Lewis, Kim

doi:10.1038/s41564-022-01227-4

Cited by 80 publications

(91 citation statements)

References 81 publications

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“…Another recently reported novel RiPP dynobactin A (WNSNVHSYRF) (Figure ), exhibiting potent anti-Gram-negative bacteria activity, was identified from Photorhabdus australis by computational analysis of BGCs distantly related to darobactins . Despite possessing an unrelated structural scaffold to darobactins, dynobactin A performs antimicrobial activity also by binding to BamA.…”

Section: Ripps Against Gram-negative Bacteriamentioning

confidence: 99%

“…Despite possessing an unrelated structural scaffold to darobactins, dynobactin A performs antimicrobial activity also by binding to BamA. Although it obstructs the function of Bam complex at a lower IC 50 value than darobactin A and B, the MIC values of dynobactin A were about 4-fold higher than darobactin A . This might be attributed to the lower permeation of dynobactin A to the outer membrane.…”

Section: Ripps Against Gram-negative Bacteriamentioning

confidence: 99%

“…108 Another recently reported novel RiPP dynobactin A (WNSNVHSYRF) (Figure 13), exhibiting potent anti-Gramnegative bacteria activity, was identified from Photorhabdus australis by computational analysis of BGCs distantly related to darobactins. 109 Despite possessing an unrelated structural scaffold to darobactins, dynobactin A performs antimicrobial activity also by binding to BamA. Although it obstructs the function of Bam complex at a lower IC 50 value than darobactin A and B, the MIC values of dynobactin A were about 4-fold higher than darobactin A.…”

Section: Darobactins/dynobactinsmentioning

confidence: 99%

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Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides

Zhong

Wang

Yan

et al. 2022

ACS Bio Med Chem Au

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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are of increasing interest in natural products as well as drug discovery. This empowers not only the unique chemical structures and topologies in natural products but also the excellent bioactivities such as antibacteria, antifungi, antiviruses, and so on. Advances in genomics, bioinformatics, and chemical analytics have promoted the exponential increase of RiPPs as well as the evaluation of biological activities thereof. Furthermore, benefiting from their relatively simple and conserved biosynthetic logic, RiPPs are prone to be engineered to obtain diverse analogues that exhibit distinct physiological activities and are difficult to synthesize. This Review aims to systematically address the variety of biological activities and/or the mode of mechanisms of novel RiPPs discovered in the past decade, albeit the characteristics of selective structures and biosynthetic mechanisms are briefly covered as well. Almost one-half of the cases are involved in anti-Gram-positive bacteria. Meanwhile, an increasing number of RiPPs related to anti-Gram-negative bacteria, antitumor, antivirus, etc., are also discussed in detail. Last but not least, we sum up some disciplines of the RiPPs' biological activities to guide genome mining as well as drug discovery and optimization in the future.

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Section: Ripps Against Gram-negative Bacteriamentioning

confidence: 99%

Section: Ripps Against Gram-negative Bacteriamentioning

confidence: 99%

Section: Darobactins/dynobactinsmentioning

confidence: 99%

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Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides

Zhong

Wang

Yan

et al. 2022

ACS Bio Med Chem Au

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“…Together with the natural products darobactin and dynobactin, produced by Photorhabdus, the discovery of these antibiotics has revealed bacterial symbionts of invertebrates to be reservoirs of potent antibacterial metabolites. [15][16][17] Additionally, improved culturing approaches like the use of isolation chip (iChip) technology, which led to the discovery of teixobactin, allow for the culturing of previously unculturable bacterial antibiotic producers (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Ribosome-targeting antibiotics and resistance via ribosomal RNA methylation

et al. 2023

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“…The screening of chemical compound libraries is a mainstay for the identification of drugs and the validation of putative targets. Examples of recent developments in antibiotics research include drug repurposing [1,2], computational methods [3], and tapping previously unaddressed sources [4].…”

Section: Introductionmentioning

confidence: 99%

A Screen Reveals Bexarotene, Sorafenib and Certain of its Analogues as Common and Effective Inhibitors of Growth of Bacteria that Grow on LB but not on McConkey Agar

Scheerer¹

2023

Preprint

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A screen of 61 compounds identified bexarotene and sorafenib as inhibitors of bacterial isolates that grew on LB agar but not on McConkey agar. The effect of bexarotene was durable, whereas sorafenib simply retarded growth. Two sorafenib analogues, previously not described, dubbed JSR-A40 and JSR-N42, displayed durable effects. Upon extending this to a larger group of bacteria from different sources it was found that both bexarotene and JSR-N42 were active in concentrations from between 1.25-10 microM in 42 of bacteria growing in LB but not McConkey medium, whereas bacteria growing on McConkey agar were all found to be insensitive at that concentration. Both bexarotene and N42 displayed rather broad characteristics similar to clindamycin, however non-overlapping. Sensitivity to clindamycin, if observed, was generally higher. It was found that the urea type compound N42 at 5 microM was broader active than clindamycin at 5 microM in this set of isolates.

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Computational identification of a systemic antibiotic for Gram-negative bacteria

Cited by 80 publications

References 81 publications

Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides

Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides

Ribosome-targeting antibiotics and resistance via ribosomal RNA methylation

A Screen Reveals Bexarotene, Sorafenib and Certain of its Analogues as Common and Effective Inhibitors of Growth of Bacteria that Grow on LB but not on McConkey Agar

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