A metagenomic analysis for combination therapy of multiple classes of antibiotics on the prevention of the spread of antibiotic-resistant genes
Antibiotics used systemically to treat infections may have off-target effects on the gut microbiome, potentially resulting in the emergence of drug-resistant bacteria or selection of pathogenic species. These organisms may present a risk to the host and spread to the environment with a risk of transmission in the community. To investigate the risk of emergent antibiotic resistance in the gut microbiome following systemic treatment with antibiotics, this metagenomic analysis project used next-generation sequencing, a custom-built metagenomics pipeline, and differential abundance analysis to study the effect of antibiotics (ampicillin, ciprofloxacin, and fosfomycin) in monotherapy and different combinations at high and low doses, to determine the effect on resistome and taxonomic composition in the gut of Balb/c mice. The results showed that low-dose monotherapy treatments showed little change in microbiome composition but did show an increase in expression of many antibiotic-resistant genes (ARGs) posttreatment. Dual combination treatments allowed the emergence of some conditionally pathogenic bacteria and some increase in the abundance of ARGs despite a general decrease in microbiota diversity. Triple combination treatment was the most successful in inhibiting emergence of relevant opportunistic pathogens and completely suppressed all ARGs after 72 h of treatment. The relative abundances of mobile genetic elements that can enhance transmission of antibiotic resistance either decreased or remained the same for combination therapy while increasing for low-dose monotherapy. Combination therapy prevented the emergence of ARGs and decreased bacterial diversity, while low-dose monotherapy treatment increased ARGs and did not greatly change bacterial diversity.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Gut microbes - 15(2023), 2 vom: 13. Dez., Seite 2271150 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Igo, Matthew [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
5E8K9I0O4U |
|---|
| Anmerkungen: |
Date Completed 02.11.2023 Date Revised 07.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/19490976.2023.2271150 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM364000341 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM364000341 | ||
| 003 | DE-627 | ||
| 005 | 20231226094532.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/19490976.2023.2271150 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1213.xml |
| 035 | |a (DE-627)NLM364000341 | ||
| 035 | |a (NLM)37908118 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Igo, Matthew |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A metagenomic analysis for combination therapy of multiple classes of antibiotics on the prevention of the spread of antibiotic-resistant genes |
| 264 | 1 | |c 2023 | |
| 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 02.11.2023 | ||
| 500 | |a Date Revised 07.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Antibiotics used systemically to treat infections may have off-target effects on the gut microbiome, potentially resulting in the emergence of drug-resistant bacteria or selection of pathogenic species. These organisms may present a risk to the host and spread to the environment with a risk of transmission in the community. To investigate the risk of emergent antibiotic resistance in the gut microbiome following systemic treatment with antibiotics, this metagenomic analysis project used next-generation sequencing, a custom-built metagenomics pipeline, and differential abundance analysis to study the effect of antibiotics (ampicillin, ciprofloxacin, and fosfomycin) in monotherapy and different combinations at high and low doses, to determine the effect on resistome and taxonomic composition in the gut of Balb/c mice. The results showed that low-dose monotherapy treatments showed little change in microbiome composition but did show an increase in expression of many antibiotic-resistant genes (ARGs) posttreatment. Dual combination treatments allowed the emergence of some conditionally pathogenic bacteria and some increase in the abundance of ARGs despite a general decrease in microbiota diversity. Triple combination treatment was the most successful in inhibiting emergence of relevant opportunistic pathogens and completely suppressed all ARGs after 72 h of treatment. The relative abundances of mobile genetic elements that can enhance transmission of antibiotic resistance either decreased or remained the same for combination therapy while increasing for low-dose monotherapy. Combination therapy prevented the emergence of ARGs and decreased bacterial diversity, while low-dose monotherapy treatment increased ARGs and did not greatly change bacterial diversity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Metagenomic analysis | |
| 650 | 4 | |a antibiotic-resistant genes | |
| 650 | 4 | |a antibiotics | |
| 650 | 4 | |a combination therapy | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Ampicillin |2 NLM | |
| 650 | 7 | |a 7C782967RD |2 NLM | |
| 650 | 7 | |a Ciprofloxacin |2 NLM | |
| 650 | 7 | |a 5E8K9I0O4U |2 NLM | |
| 700 | 1 | |a Xu, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Krishna, Ashok |e verfasserin |4 aut | |
| 700 | 1 | |a Stewart, Sharron |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhihua |e verfasserin |4 aut | |
| 700 | 1 | |a Weaver, James L |e verfasserin |4 aut | |
| 700 | 1 | |a Stone, Heather |e verfasserin |4 aut | |
| 700 | 1 | |a Sacks, Leonard |e verfasserin |4 aut | |
| 700 | 1 | |a Bensman, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Florian, Jeffry |e verfasserin |4 aut | |
| 700 | 1 | |a Rouse, Rodney |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Xiaomei |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Gut microbes |d 2010 |g 15(2023), 2 vom: 13. Dez., Seite 2271150 |w (DE-627)NLM199892369 |x 1949-0984 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2023 |g number:2 |g day:13 |g month:12 |g pages:2271150 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/19490976.2023.2271150 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2023 |e 2 |b 13 |c 12 |h 2271150 | ||