In-Source CID Ramping and Covariant Ion Analysis of Hydrophilic Interaction Chromatography Metabolomics

Su, Xiaoyang; Chiles, Eric; Maimouni, Sara; Wondisford, Fredric E.; Zong, Wei‐Xing; Song, Chi

doi:10.1021/acs.analchem.9b04181

Cited by 30 publications

(25 citation statements)

References 24 publications

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“…Our results suggest that a single MS 2 spectrum may contain irrelevant m/z signals and the pseudospectrum, generated by correlating multiple MS 2 spectra to the MS 1 -extracted ion chromatogram, is an effective approach to "clean" the MS 2 spectrum. The pseudospectra were generated using a modified version of COVINA (45).…”

Section: Parallel Reaction Monitoring Msmentioning

confidence: 99%

Metabolomic shifts associated with heat stress in coral holobionts

et al. 2021

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Understanding the response of the coral holobiont to environmental change is crucial to inform conservation efforts. The most pressing problem is “coral bleaching,” usually precipitated by prolonged thermal stress. We used untargeted, polar metabolite profiling to investigate the physiological response of the coral species Montipora capitata and Pocillopora acuta to heat stress. Our goal was to identify diagnostic markers present early in the bleaching response. From the untargeted UHPLC-MS data, a variety of co-regulated dipeptides were found that have the highest differential accumulation in both species. The structures of four dipeptides were determined and showed differential accumulation in symbiotic and aposymbiotic (alga-free) populations of the sea anemone Aiptasia (Exaiptasia pallida), suggesting the deep evolutionary origins of these dipeptides and their involvement in symbiosis. These and other metabolites may be used as diagnostic markers for thermal stress in wild coral.

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Section: Parallel Reaction Monitoring Msmentioning

confidence: 99%

Metabolomic shifts associated with heat stress in coral holobionts

et al. 2021

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“…Supernatants were analyzed via the methods of Su et al (2020). Specificity was achieved through a combination of chromatographic separations followed by high-resolution MS.…”

Section: Discussionmentioning

confidence: 99%

Disruption of the MreB Elongasome Is Overcome by Mutations in the Tricarboxylic Acid Cycle

2021

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The bacterial actin homolog, MreB, is highly conserved among rod-shaped bacteria and essential for growth under normal growth conditions. MreB directs the localization of cell wall synthesis and loss of MreB results in round cells and death. Using the MreB depolymerizing drug, A22, we show that changes to central metabolism through deletion of malate dehydrogenase from the tricarboxylic acid (TCA) cycle results in cells with an increased tolerance to A22. We hypothesize that deletion of malate dehydrogenase leads to the upregulation of gluconeogenesis resulting in an increase in cell wall precursors. Consistent with this idea, metabolite analysis revealed that malate dehydrogenase (mdh) deletion cells possess elevated levels of several glycolysis/gluconeogenesis compounds and the cell wall precursor, uridine diphosphate N-acetylglucosamine (UDP-NAG). In agreement with these results, the increased A22 resistance phenotype can be recapitulated through the addition of glucose to the media. Finally, we show that this increase in antibiotic tolerance is not specific to A22 but also applies to the cell wall-targeting antibiotic, mecillinam.

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“…Supernatants were analyzed via the methods of Su et al (Su, Chiles et al 2020). Specificity was achieved through a combination of chromatographic separations followed by high-resolution MS.…”

Section: Methodsmentioning

confidence: 99%

Disruption of the MreB elongasome is overcome by mutations in the TCA cycle

Barton

Grinnell

Morgenstein

2020

Preprint

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24Antibiotic resistant bacteria are a global threat to human health. One way to combat the 25 rise of antibiotic resistance is to make new antibiotics that target previously ignored 26 proteins. The bacterial actin homolog, MreB, is highly conserved among rod-shaped 27 bacteria and essential for growth, making MreB a good focus for antibiotic targeting. 28 Therefore, it is imperative to understand mechanisms that can give rise to resistance to 29 MreB targeting drugs. Using the MreB targeting drug, A22, we show that changes to 30 central metabolism through deletion of TCA cycle genes, leads to the upregulation of 31 gluconeogenesis resulting in cells with an increased minimal inhibitory concentration to 32 A22. This phenotype can be recapitulated through the addition of glucose to the media. 33Finally, we show that this increase in minimal inhibitory concentration is not specific to 34 A22 but can be seen in other cell wall targeting antibiotics, such as mecillinam. 35 36 Importance 37The spread of antibiotic resistance has made bacterial infections harder to treat. Finding 38 new targets for antibiotic development is critical to overcoming the variety of resistance 39 mechanism that are already crippling our ability to treat infections with current 40 antibiotics. The bacterial actin homolog MreB is a good target for new antibiotic 41 development because it is essential for growth and highly conserved among rod-shaped 42 pathogens. The significance of this research is in understanding the mechanisms cells 43 can develop toward the inhibition of MreB to better understand how to make MreB 44 targeting antibiotics in the future. 45Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, and Vibrio cholerae 63 (7, 8). Therefore, MreB is a good target candidate for new antibiotic development. While 64 there are no current FDA-approved MreB-targeting antibiotics, the compound A22 is 65 used in laboratory settings to study the role of MreB in the cell. A22 binds adjacent to 66 the ATP binding pocket of MreB and alters its polymerization dynamics (9-13). MreB 67 directs the localization of cell wall synthesis, and disruption of MreB, either through the 68 use of A22 or genetic modifications, causes cells to become misshapen and lyse. One 69

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In-Source CID Ramping and Covariant Ion Analysis of Hydrophilic Interaction Chromatography Metabolomics

Cited by 30 publications

References 24 publications

Metabolomic shifts associated with heat stress in coral holobionts

Metabolomic shifts associated with heat stress in coral holobionts

Disruption of the MreB Elongasome Is Overcome by Mutations in the Tricarboxylic Acid Cycle

Disruption of the MreB elongasome is overcome by mutations in the TCA cycle

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