Direct affinity screening chromatography–mass spectrometry assay for identification of antibacterial agents from natural product sources

Schug, Kevin A.; Wang, Evelyn; Shen, Sijia; Rao, Sunaina; Smith, Sally J.; Hunt, Laura R.; Mydlarz, Laura D.

doi:10.1016/j.aca.2011.11.038

Cited by 12 publications

(5 citation statements)

References 25 publications

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“…Caribbean gorgonians may rely on other mechanisms, such as inducible immune defenses [22,23,42,43] or QS, for microbial regulation. Nonetheless, the presence of strong antimicrobial activity against human pathogens is notable for the potential of development of novel antimicrobial therapies, especially against antibiotic resistant bacterial strains [44]. …”

Section: Discussionmentioning

confidence: 99%

Microbial Regulation in Gorgonian Corals

et al. 2012

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Gorgonian corals possess many novel natural products that could potentially mediate coral-bacterial interactions. Since many bacteria use quorum sensing (QS) signals to facilitate colonization of host organisms, regulation of prokaryotic cell-to-cell communication may represent an important bacterial control mechanism. In the present study, we examined extracts of twelve species of Caribbean gorgonian corals, for mechanisms that regulate microbial colonization, such as antibacterial activity and QS regulatory activity. Ethanol extracts of gorgonians collected from Puerto Rico and the Florida Keys showed a range of both antibacterial and QS activities using a specific Pseudomonas aeruginosa QS reporter, sensitive to long chain AHLs and a short chain N-acylhomoserine lactones (AHL) biosensor, Chromobacterium violaceium. Overall, the gorgonian corals had higher antimicrobial activity against non-marine strains when compared to marine strains. Pseudopterogorgia americana, Pseusopterogorgia acerosa, and Pseudoplexuara flexuosa had the highest QS inhibitory effect. Interestingly, Pseudoplexuara porosa extracts stimulated QS activity with a striking 17-fold increase in signal. The stimulation of QS by P. porosa or other elements of the holobiont may encourage colonization or recruitment of specific microbial species. Overall, these results suggest the presence of novel stimulatory QS, inhibitory QS and bactericidal compounds in gorgonian corals. A better understanding of these compounds may reveal insight into coral-microbial ecology and whether a therapeutic potential exists.

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Section: Discussionmentioning

confidence: 99%

Microbial Regulation in Gorgonian Corals

et al. 2012

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“…In the simplest case, microbial growth directly results in an easily detectable signal (such as changes in absorption, fluorescence or bioluminescence). More complex techniques using tools such as microfluidics, fluorescence polarization activity assays or mass spectrometry have been developed that enable rapid and large-scale analysis and allow the screening of compounds for their ability to specifically interact with a given drug target, or use MIC shift assays to detect hypersensitive or resistant mutants and thereby control for compound specificity [137][138][139][140][141] .…”

Section: Ab5: Feasibilitymentioning

confidence: 99%

Improving target assessment in biomedical research: the GOT-IT recommendations

Emmerich¹,

Martínez-Gamboa

Hofmann

et al. 2020

Nat Rev Drug Discov

111

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Academic research plays a key role in identifying new drug targets, including understanding target biology and links between targets and disease states. To lead to new drugs, however, research must progress from purely academic exploration to the initiation of efforts to identify and test a drug candidate in clinical trials, which are typically conducted by the biopharma industry. This transition can be facilitated by a timely focus on target assessment aspects such as target-related safety issues, druggability and assayability, as well as the potential for target modulation to achieve differentiation from established therapies. Here, we present recommendations from the GOT-IT working group, which have been designed to support academic scientists and funders of translational research in identifying and prioritizing target assessment activities and in defining a critical path to reach scientific goals as well as goals related to licensing, partnering with industry or initiating clinical development programmes. Based on sets of guiding questions for different areas of target assessment, the GOT-IT framework is intended to stimulate academic scientists’ awareness of factors that make translational research more robust and efficient, and to facilitate academia–industry collaboration.

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“…For example, in the work by Raji et al [37], this assumption was demonstrated to be a poor one for assessing binding between a series of similarly sized peptides. In the case of vancomycin binding, the tripeptide bacterial cell wall model, this assumption has been shown to be reasonably valid [9]. In fact, this assumption was also made by Jørgensen et al [1], where they considered that the response factor for the doubly protonated antibiotic-peptide complex was similar to the response factor for the doubly protonated Bfree^antibiotic.…”

Section: Equimolar Binding Modelmentioning

confidence: 76%

“…Numerous studies about noncovalent binding determination between vancomycin and different cell wall model targets have been performed [1,3,[5][6][7]. In an effort to build from the knowledge gained, this model has also been used to facilitate the discovery of new antibiotic leads that might exhibit their activity through the same mechanism [8,9].…”

Section: Introductionmentioning

confidence: 99%

Determination of Noncovalent Binding Using a Continuous Stirred Tank Reactor as a Flow Injection Device Coupled to Electrospray Ionization Mass Spectrometry

Santos

Waybright

Fan

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. Described is a new method based on the concept of controlled band dispersion, achieved by hyphenating flow injection analysis with ESI-MS for noncovalent binding determinations. A continuous stirred tank reactor (CSTR) was used as a FIA device for exponential dilution of an equimolar host-guest solution over time. The data obtained was treated for the noncovalent binding determination using an equimolar binding model. Dissociation constants between vancomycin and AcLys(Ac)-Ala-Ala-OH peptide stereoisomers were determined using both the positive and negative ionization modes. The results obtained for Ac-L-Lys(Ac)-D-Ala-D-Ala (a model for a Gram-positive bacterial cell wall) binding were in reasonable agreement with literature values made by other mass spectrometry binding determination techniques. Also, the developed method allowed the determination of dissociation constants for vancomycin with Ac-L-Lys(Ac)-D-Ala-L-Ala, Ac-L-Lys(Ac)-L-Ala-D-Ala, and Ac-L-Lys(Ac)-L-Ala-L-Ala. Although some differences in measured binding affinities were noted using different ionization modes, the results of each determination were generally consistent. Differences are likely attributable to the influence of a pseudo-physiological ammonium acetate buffer solution on the formation of positively-and negatively-charged ionic complexes.

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Direct affinity screening chromatography–mass spectrometry assay for identification of antibacterial agents from natural product sources

Cited by 12 publications

References 25 publications

Microbial Regulation in Gorgonian Corals

Microbial Regulation in Gorgonian Corals

Improving target assessment in biomedical research: the GOT-IT recommendations

Determination of Noncovalent Binding Using a Continuous Stirred Tank Reactor as a Flow Injection Device Coupled to Electrospray Ionization Mass Spectrometry

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