Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs
Rates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensa...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-06-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2013.00145/full |
| _version_ | 1818049907987054592 |
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| author | Erica C. Pehrsson Kevin J. Forsberg Molly K. Gibson Sara eAhmadi Sara eAhmadi Gautam eDantas Gautam eDantas Gautam eDantas |
| author_facet | Erica C. Pehrsson Kevin J. Forsberg Molly K. Gibson Sara eAhmadi Sara eAhmadi Gautam eDantas Gautam eDantas Gautam eDantas |
| author_sort | Erica C. Pehrsson |
| collection | DOAJ |
| description | Rates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensal, and environmental organisms, prompting deeper investigation of natural and human-associated reservoirs of antibiotic resistance. Functional metagenomic selections, in which shotgun-cloned DNA fragments are selected for their ability to confer survival to an indicator host, have been increasingly applied to the characterization of many antibiotic resistance reservoirs. These experiments have demonstrated that antibiotic resistance genes are highly diverse and widely distributed, many times bearing little to no similarity to known sequences. Through unbiased selections for survival to antibiotic exposure, functional metagenomics can improve annotations by reducing the discovery of false-positive resistance and by allowing for the identification of previously unrecognizable resistance genes. In this review, we summarize the novel resistance functions uncovered using functional metagenomic investigations of natural and human-impacted resistance reservoirs. Examples of novel antibiotic resistance genes include those highly divergent from known sequences, those for which sequence is entirely unable to predict resistance function, bifunctional resistance genes, and those with unconventional, atypical resistance mechanisms. Overcoming antibiotic resistance in the clinic will require a better understanding of existing resistance reservoirs and the dissemination networks that govern horizontal gene exchange, informing best practices to limit the spread of resistance-conferring genes to human pathogens. |
| first_indexed | 2024-12-10T10:45:03Z |
| format | Article |
| id | doaj.art-1090531baaee430693943b1b01702801 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-10T10:45:03Z |
| publishDate | 2013-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-1090531baaee430693943b1b017028012022-12-22T01:52:10ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2013-06-01410.3389/fmicb.2013.0014552519Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirsErica C. Pehrsson0Kevin J. Forsberg1Molly K. Gibson2Sara eAhmadi3Sara eAhmadi4Gautam eDantas5Gautam eDantas6Gautam eDantas7Washington University School of Medicine in St. LouisWashington University School of Medicine in St. LouisWashington University School of Medicine in St. LouisWashington University School of Medicine in St. LouisWashington University School of Medicine in St. LouisWashington University School of Medicine in St. LouisWashington University School of Medicine in St. LouisWashington University School of Medicine in St. LouisRates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensal, and environmental organisms, prompting deeper investigation of natural and human-associated reservoirs of antibiotic resistance. Functional metagenomic selections, in which shotgun-cloned DNA fragments are selected for their ability to confer survival to an indicator host, have been increasingly applied to the characterization of many antibiotic resistance reservoirs. These experiments have demonstrated that antibiotic resistance genes are highly diverse and widely distributed, many times bearing little to no similarity to known sequences. Through unbiased selections for survival to antibiotic exposure, functional metagenomics can improve annotations by reducing the discovery of false-positive resistance and by allowing for the identification of previously unrecognizable resistance genes. In this review, we summarize the novel resistance functions uncovered using functional metagenomic investigations of natural and human-impacted resistance reservoirs. Examples of novel antibiotic resistance genes include those highly divergent from known sequences, those for which sequence is entirely unable to predict resistance function, bifunctional resistance genes, and those with unconventional, atypical resistance mechanisms. Overcoming antibiotic resistance in the clinic will require a better understanding of existing resistance reservoirs and the dissemination networks that govern horizontal gene exchange, informing best practices to limit the spread of resistance-conferring genes to human pathogens.http://journal.frontiersin.org/Journal/10.3389/fmicb.2013.00145/fullantibiotic resistancefunctional metagenomicsbifunctional resistance geneenvironmental resistanceresistance reservoirtransferable resistance |
| spellingShingle | Erica C. Pehrsson Kevin J. Forsberg Molly K. Gibson Sara eAhmadi Sara eAhmadi Gautam eDantas Gautam eDantas Gautam eDantas Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs Frontiers in Microbiology antibiotic resistance functional metagenomics bifunctional resistance gene environmental resistance resistance reservoir transferable resistance |
| title | Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs |
| title_full | Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs |
| title_fullStr | Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs |
| title_full_unstemmed | Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs |
| title_short | Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs |
| title_sort | novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs |
| topic | antibiotic resistance functional metagenomics bifunctional resistance gene environmental resistance resistance reservoir transferable resistance |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2013.00145/full |
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