Upregulated Palmitoleate and Oleate Production in <i>Escherichia coli</i> Promotes Gentamicin Resistance

Metabolic reprogramming mediates antibiotic efficacy. However, metabolic adaptation of microbes evolving from antibiotic sensitivity to resistance remains undefined. Therefore, untargeted metabolomics was conducted to unveil relevant metabolic reprogramming and potential intervention targets involved in gentamicin resistance. In total, 61 metabolites and 52 metabolic pathways were significantly altered in gentamicin-resistant E. coli. Notably, the metabolic reprogramming was characterized by decreases in most metabolites involved in carbohydrate and amino acid metabolism, and accumulation of building blocks for nucleotide synthesis in gentamicin-resistant E. coli. Meanwhile, fatty acid metabolism and glycerolipid metabolism were also significantly altered in gentamicin-resistant E. coli. Additionally, glycerol, glycerol-3-phosphate, palmitoleate, and oleate were separately defined as the potential biomarkers for identifying gentamicin resistance in E. coli. Moreover, palmitoleate and oleate could attenuate or even abolished killing effects of gentamicin on E. coli, and separately increased the minimum inhibitory concentration of gentamicin against E. coli by 2 and 4 times. Furthermore, palmitoleate and oleate separately decreased intracellular gentamicin contents, and abolished gentamicin-induced accumulation of reactive oxygen species, indicating involvement of gentamicin metabolism and redox homeostasis in palmitoleate/oleate-promoted gentamicin resistance in E. coli. This study identifies the metabolic reprogramming, potential biomarkers and intervention targets related to gentamicin resistance in bacteria

Location and topography of the Heihe River Basin, China.

<p>Location and topography of the Heihe River Basin, China.</p

Daily NPP for a 10-day period of Heihe River Basin.

<p>(a) DOY 131–140. (b) DOY 161–170. (c) DOY 191–200. (d) DOY 221–230. (e) DOY 251–260. (f) DOY 281–290.</p

Temporal dynamic patterns of modelled and ground based GPP during the growing season of 2012.

<p>(a) croplands. (b)orchard. (c)vegetable field. (d)wetland.</p

Land surface conditions around the EC sites.

<p>(a) orchard. (b) vegetable field.</p

Spatial distribution of field sampling sites.

<p>Spatial distribution of field sampling sites.</p

Temporal dynamic patterns of modelled GPP generated with simulated daily LAI and FPAR together with ground based ones during the growing season of 2012.

<p>(a) croplands. (b) orchard. (c) vegetable field. (d) wetland. For modelled and ground-based values, error bars represent mean and maximum/minimum for GPP in a 10-day period.</p

Model test against ground-based GPP.

<p>(a) Relationship between estimated GPP and ground-based GPP. (b) Relationship between MODIS GPP and ground-based GPP (b).</p