Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics
Numerous nonantibiotic drugs have potent antibacterial activity and can adversely affect the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Network-based analysis of drug-drug similarities revealed that antibiotics clustered into modules that are consistent with the mode of action of their established classes, whereas nonantibiotics remained unconnected. Half of the nonantibiotics clustered into separate modules, potentially revealing shared and unexploited targets for new antimicrobials. Analysis of efflux systems revealed that they widely affect antibiotics and nonantibiotics alike, suggesting that the impact of nonantibiotics on antibiotic cross-resistance should be investigated closely in vivo.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:384 |
|---|---|
| Enthalten in: |
Science (New York, N.Y.) - 384(2024), 6691 vom: 05. Apr., Seite 93-100 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Noto Guillen, Mariana [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 17.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1126/science.adk7368 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369737342 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369737342 | ||
| 003 | DE-627 | ||
| 005 | 20240418232745.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240315s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1126/science.adk7368 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1379.xml |
| 035 | |a (DE-627)NLM369737342 | ||
| 035 | |a (NLM)38484036 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Noto Guillen, Mariana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.04.2024 | ||
| 500 | |a Date Revised 17.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Numerous nonantibiotic drugs have potent antibacterial activity and can adversely affect the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Network-based analysis of drug-drug similarities revealed that antibiotics clustered into modules that are consistent with the mode of action of their established classes, whereas nonantibiotics remained unconnected. Half of the nonantibiotics clustered into separate modules, potentially revealing shared and unexploited targets for new antimicrobials. Analysis of efflux systems revealed that they widely affect antibiotics and nonantibiotics alike, suggesting that the impact of nonantibiotics on antibiotic cross-resistance should be investigated closely in vivo | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Anti-Infective Agents |2 NLM | |
| 700 | 1 | |a Li, Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Rosener, Brittany |e verfasserin |4 aut | |
| 700 | 1 | |a Mitchell, Amir |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Science (New York, N.Y.) |d 1880 |g 384(2024), 6691 vom: 05. Apr., Seite 93-100 |w (DE-627)NLM000023450 |x 1095-9203 |7 nnns |
| 773 | 1 | 8 | |g volume:384 |g year:2024 |g number:6691 |g day:05 |g month:04 |g pages:93-100 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1126/science.adk7368 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 384 |j 2024 |e 6691 |b 05 |c 04 |h 93-100 | ||