Evolution of antibiotic resistance at low antibiotic concentrations: selection below the minimal selective concentration
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ABSTRACT:
PROVIDER: PRJEB38942 | ENA |
REPOSITORIES: ENA
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Project description:Determining the selective potential of antibiotics at environmental concentrations is critical for designing effective strategies to limit selection for antibiotic resistance. This study determined the minimal selective concentrations (MSCs) for macrolide and fluoroquinolone antibiotics included on the European Commission's Water Framework Directive's priority hazardous substances Watch List. The macrolides demonstrated positive selection for ermF at concentrations 1-2 orders of magnitude greater (>500 and <750 µg/L) than measured environmental concentrations (MECs). Ciprofloxacin illustrated positive selection for intI1 at concentrations similar to current MECs (>7.8 and <15.6 µg/L). This highlights the need for compound specific assessment of selective potential. In addition, a sub-MSC selective window defined by the minimal increased persistence concentration (MIPC) is described. Differential rates of negative selection (or persistence) were associated with elevated prevalence relative to the no antibiotic control below the MSC. This increased persistence leads to opportunities for further selection over time and risk of human exposure and environmental transmission.
| S-EPMC7471295 | biostudies-literature
Project description:The human pathogenic bacterium Listeria monocytogenes was exposed to antibiotics both during clinical treatment and as a saprophyte. As one of the keys to successful treatment is continued antibiotic sensitivity, the purpose of this study was to determine if exposure to sublethal antibiotic concentrations would affect the bacterial physiology and potentially induce tolerance to antibiotics. Transcriptomic analyses demonstrated that each of four antibiotics caused a compound-specific gene expression pattern related to (the) mode-of-action of the particular antibiotic. All four antibiotics caused the same changes in expression of several metabolic genes indicating a shift from aerobic to anaerobic metabolism driven by the induction of lmo1634 and the repression of alsA and lmo1992. This shift in metabolism could be a survival strategy in response to antibiotics and is further supported by the observation that a Δlmo1634 mutant was more sensitive to bactericidal antibiotics. The monocin locus encoding a cryptic prophage was induced by co-trimoxazole and repressed by ampicillin and gentamicin. This expression pattern correlated with the observed antibiotic-dependent biofilm formation, indicating a role of monocin in antibiotic-induced biofilm formation and a ΔlmaDCBA mutant confirmed this correlation. Thus, sublethal concentrations of antibiotics caused metabolic and physiological changes indicating that the organism is preparing to withstand lethal concentrations of antibiotics.
2016-06-01 | GSE65558 | GEO
Project description:The human pathogenic bacterium Listeria monocytogenes was exposed to antibiotics both during clinical treatment and as a saprophyte. As one of the keys to successful treatment is continued antibiotic sensitivity, the purpose of this study was to determine if exposure to sublethal antibiotic concentrations would affect the bacterial physiology and potentially induce tolerance to antibiotics. Transcriptomic analyses demonstrated that each of four antibiotics caused a compound-specific gene expression pattern related to (the) mode-of-action of the particular antibiotic. All four antibiotics caused the same changes in expression of several metabolic genes indicating a shift from aerobic to anaerobic metabolism driven by the induction of lmo1634 and the repression of alsA and lmo1992. This shift in metabolism could be a survival strategy in response to antibiotics and is further supported by the observation that a Îlmo1634 mutant was more sensitive to bactericidal antibiotics. The monocin locus encoding a cryptic prophage was induced by co-trimoxazole and repressed by ampicillin and gentamicin. This expression pattern correlated with the observed antibiotic-dependent biofilm formation, indicating a role of monocin in antibiotic-induced biofilm formation and a ÎlmaDCBA mutant confirmed this correlation. Thus, sublethal concentrations of antibiotics caused metabolic and physiological changes indicating that the organism is preparing to withstand lethal concentrations of antibiotics. Investigation of mRNA and sRNA expression profiles of L. monocytogenes EGD cells exposed to sublethal concentrations of four different antibiotics i.e. ampicillin, tetracycline, gentamicin and co-trimoxazole for 3h.
2016-06-01 | E-GEOD-65558 | biostudies-arrayexpress
Project description:Lincomycin is a lincosamide antibiotic that forms cross-links within the peptidyl transferase loop region of the 23S rRNA of the 50S subunit of the bacterial ribosome, thereby inhibiting protein synthesis. We have previously reported that lincomycin at concentrations below the minimum inhibitory concentration potentiates the production of secondary metabolites in actinomycete strains. We aimed to elucidate the fundamental mechanisms underlying lincomycin induction of secondary metabolism in actinomycetes. Therefore, the dose-dependent response of lincomycin on gene expression of the model actinomycetes Streptomyces coelicolor A3(2) and possible relationships to secondary metabolism have been investigated.
2018-03-02 | E-MTAB-6434 | biostudies-arrayexpress
Project description:To determine dose-dependent effects of metal exposure we performed microarray hybridizations with RNA isolated from Daphnia magna following Cu, Cd, and Zn exposures over a range of concentrations that included a tolerated concentration, a sublethal concentration, and a highly toxic concentration. The gene expression profiles revealed effects to digestion related genes, immune related genes, metallothioneins, and oxidative stress genes at the higher concentrations. We also observed that the highest concentrations produced less specific gene expression profiles than the lower concentrations suggesting a more general stress response at the higher concentrations. The lowest concentration tested, representing tolerated concentrations of the metals, caused differential expression of only a few genes and were distinct from the expression profiles of the higher concentrations. This result provides support for the presence of a No Observed Transcriptional Effect Level (NOTEL) for metal exposure in D. magna and suggests that gene expression analysis may offer a strategy for distinguishing between toxic and nontoxic concentrations of metals in the environment. Keywords: ecotoxicogenomic exposure study
2008-06-09 | GSE7668 | GEO
Project description:The marine bacterium Phaeobacter inhibens produces tropodithietic acid (TDA), a broad-spectrum antibiotic and anticancer agent. TDA allows P. inhibens to antagonize other bacteria, including several pathogens, and eukaryotes. Since recently antibiotics are also discussed to function as intermicrobial signals. Here we show that ~10% of the genes of P. inhibens are strongly influenced by N-acyl-homoserine lactone (AHL) mediated quorum sensing (QS), switching the bacteriumâs life style from attached to free-living. In an AHL negative mutant of P. inhibens subinhibitory concentrations of TDA caused the same regulatory effect as the AHL. This demonstrates that bacteria can produce antibiotic compounds not only as weapons, but also to substitute their endogenous AHL molecule in QS. The dual function of TDA probably supports the QS system to accelerate regulatory processes and points to a so far neglected role of antibiotics at subinhibitory concentrations in the environment and in microbial interactions. Comparison of whole transcriptomes of wildytype, quorum sensing mutants (pgaI and pgaR) and pgaI grown supplemented with subinhibitory concentration of the antibiotic TDA. RNA isolated in the late exponential growth phase. 4 biological replicates investigated for each strain.
2016-03-15 | E-GEOD-79173 | biostudies-arrayexpress
Project description:BackgroundMucormycosis is a destructive invasive mold infection afflicting patients with diabetes and hematologic malignancies. Patients with diabetes are often treated with statins, which have been shown to have antifungal properties. We sought to examine the effects of statins on Rhizopus oryzae, a common cause of mucormycosis.MethodsClinical strains of R. oryzae were exposed to lovastatin, atorvastatin, and simvastatin and the minimum inhibitory concentrations (MICs) were determined. R. oryzae germination, DNA fragmentation, susceptibility to oxidative stress, and ability to damage endothelial cells were assessed. We further investigated the impact of exposure to lovastatin on the virulence of R. oryzaeResultsAll statins had MICs of >64 µg/mL against R. oryzae Exposure of R. oryzae to statins decreased germling formation, induced DNA fragmentation, and attenuated damage to endothelial cells independently of the expression of GRP78 and CotH. Additionally, R. oryzae exposed to lovastatin showed macroscopic loss of melanin, yielded increased susceptibility to the oxidative agent peroxide, and had attenuated virulence in both fly and mouse models of mucormycosis.ConclusionsExposure of R. oryzae to statins at concentrations below their MICs decreased virulence both in vitro and in vivo. Further investigation is warranted into the use of statins as adjunctive therapy in mucormycosis.
| S-EPMC5007635 | biostudies-literature
Project description:mRNA-Seq of mayfly (Cloeon dipterum) exposed to different Fipronil concentrations below acute toxicity levels against untreated controls
| PRJEB61040 | ENA
Project description:Primary objectives: To determine the intratumoral concentration of osimertinib in peritoneal metastasis upon 2 weeks of treatment of patients who are candidate for CRS-HIPEC treatment (group 1), and in liver metastasis of patients who are candidate for primary liver resection (group 2). These clinical determined intratumoral osimertinib concentrations will be compared with the effective tissue concentrations in PDTOs from PM of CRC from the PDO-CRPM study.
Primary endpoints: Intratumoral osimertinib concentration in peritoneal metastasis and liver metastasis.
| 26958 | ecrin-mdr-crc
Project description:The goals of this study are to use SWATH-MS to detect bacterial proteomic profiles of wild-type Acinetobacter baylyi ADP1, and its protein response under the exposure of non-antibiotic pharmaceuticals, including ibuprofen, naproxen, gemfibrozil, diclofenac, propanolol, and iopromide. The concentrations were 0.5 mg/L for ibuprofen, naproxen, gemfibrozil, diclofenac, propanolol, and 1.0 mg/L for iopromide. The group without dosing pharmaceutical was the control group. Each concentration was conducted in triplicate. By comparing the proteomic profiles of experimental groups and control group, the effects of non-antibiotic pharmaceuticals on translational levels can be revealed.
2020-05-22 | PXD016798 | Pride