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Evolution of high-level resistance during low-level antibiotic exposure.

ABSTRACT: It has become increasingly clear that low levels of antibiotics present in many environments can select for resistant bacteria, yet the evolutionary pathways for resistance development during exposure to low amounts of antibiotics remain poorly defined. Here we show that Salmonella enterica exposed to sub-MIC levels of streptomycin evolved high-level resistance via novel mechanisms that are different from those observed during lethal selections. During lethal selection only rpsL mutations are found, whereas at sub-MIC selection resistance is generated by several small-effect resistance mutations that combined confer high-level resistance via three different mechanisms: (i) alteration of the ribosomal RNA target (gidB mutations), (ii) reduction in aminoglycoside uptake (cyoB, nuoG, and trkH mutations), and (iii) induction of the aminoglycoside-modifying enzyme AadA (znuA mutations). These results demonstrate how the strength of the selective pressure influences evolutionary trajectories and that even weak selective pressures can cause evolution of high-level resistance.

SUBMITTER: Wistrand-Yuen E

PROVIDER: S-EPMC5913237 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Evolution of high-level resistance during low-level antibiotic exposure.

Wistrand-Yuen Erik E Knopp Michael M Hjort Karin K Koskiniemi Sanna S Berg Otto G OG Andersson Dan I DI

Nature communications 20180423 1

It has become increasingly clear that low levels of antibiotics present in many environments can select for resistant bacteria, yet the evolutionary pathways for resistance development during exposure to low amounts of antibiotics remain poorly defined. Here we show that Salmonella enterica exposed to sub-MIC levels of streptomycin evolved high-level resistance via novel mechanisms that are different from those observed during lethal selections. During lethal selection only rpsL mutations are fo ...[more]

PMID: 29686259

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Project description:Uganda has experienced tick acaricide resistance in the livestock sector. With increase in incidence of tick-borne diseases (TBDs), use of antibiotics for control of TBDs and other opportunistic diseases has raisedserious concerns. The purpose of this study was to compare the farmers' tick control and antibiotic use practices on farms in regions of low (LARA) and high (HARA) tick acaricide resistance in Uganda, determine the prevalence of antibiotic residues in milk from both regions, and identify factors associated with antibiotic residues in milk. One representative district was selected from each region from which 10 farms were randomly selected. Delvotest SP-NT® test kit was used to detect antibiotic residues in milk. Half-body tick counts and acaricide efficacy tests were performed. Majority (70%) of HARA's respondents reported a corresponding increase in a monthly incidence of TBDs with an average of 3.2 cases of TBDs treated per farm compared to 0.2 cases in LARA. East Coast fever (ECF) was identified as the most common TBD in both regions, though cases of coinfection were more common in HARA. Half of HARA's respondents reported a corresponding increase in the use of antibiotics on their farms due to tick resistance compared to LARA. Antibiotics were the most used drugs on farms in both regions with oxytetracycline being the commonly used antibiotic. Ticks from HARA were resistant to deltamethrin, amitraz, and coformulation (chlorpyriphos and cypermethrin) while resistance against deltamethrin was confirmed in LARA. HARA farms had a significantly higher prevalence of antibiotic residues (21.25%) in raw milk than in LARA (4%) farms (p?<? 0.05). Acaricide resistance and practice of reading drug use instructions were significantly associated with antibiotic residues in milk at farm level. Overall, the study provides vital information linking acaricide resistance to antibiotic use practices, consequently leading to antibiotic residues in milk.

Dataset Information

Evolution of high-level resistance during low-level antibiotic exposure.

Publications

Evolution of high-level resistance during low-level antibiotic exposure.

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