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. 2022 Dec 9;7(50):46486-46493.
doi: 10.1021/acsomega.2c05288. eCollection 2022 Dec 20.

Characterization and Potentiating Effects of the Ethanolic Extracts of the Red Seaweed Gracillaria sp. on the Activity of Carbenicillin against Vibrios

Wen-Jung Lu  1 , Ya-Chin Tsui  1 , Chun-Ju Chang  1 , Pang-Hung Hsu  2   3   4 , Mei-Ying Huang  5 , Margaret Lai  1 , Yu-Wei Lian  1 , Chia-Lin Chen  1 , Hong-Ting Victor Lin  1   2
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Characterization and Potentiating Effects of the Ethanolic Extracts of the Red Seaweed Gracillaria sp. on the Activity of Carbenicillin against Vibrios

Wen-Jung Lu et al. ACS Omega. .

Abstract

β-lactam-resistant Vibrio strains are a significant clinical problem, and β-lactamase inhibitors are generally coadministered with β-lactam drugs to control drug-resistant bacteria. Seaweed is a rich source of natural bioactive compounds; however, their potential as β-lactamase inhibitors against bacterial pathogens remains unknown. Herein, we evaluated the potential β-lactamase inhibitory effect of the ethanolic extracts of the red seaweed Gracilaria sp. (GE) against four Vibrio strains. The minimum inhibitory concentration, half-maximal inhibitory concentration, checkerboard assay results, and time-kill study results indicate that GE has limited antibacterial activity but can potentiate the activity of the β-lactam antibiotic carbenicillin against Vibrio parahemolyticus and V. cholerae. We overexpressed and purified recombinant metallo-β-lactamase, VarG, from V. cholerae for in vitro studies and observed that adding GE reduced the carbenicillin and nitrocefin degradation by VarG by 20% and 60%, respectively. Angiotensin I-converting enzyme inhibition studies demonstrated that GE did not inhibit VarG via metal chelation. Toxicity assays indicated that GE exhibited mild toxicity against human cells. Through gas chromatography and mass spectrometry, we showed that GE comprises alkaloids, phenolic compounds, terpenoids, terpenes, and halogenated aromatic compounds. This study revealed that extracts of the red seaweed Gracillaria sp. can potentially inhibit β-lactamase activity.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Time-kill curve of Vibrios with CAR, GE alone, or in combination. (A) V. parahemolyticus (B) V. cholerae. Data are expressed as mean ± SD (n = 3). CAR, carbenicillin; GE, Gracillaria sp. extract. For V. parahemolyticus, CAR (64 μg/mL) and GE (7.81 μg/mL); for V. cholerae, CAR (4 μg/mL) and GE (7.81 μg/mL).
Figure 2
Figure 2
Effect of Gracilaria sp. extracts on VarG for carbenicillin degradation.
Figure 3
Figure 3
Effect of Gracilaria sp. extracts on VarG. Using nitrocefin as a substrate, and the variety of OD486 was measured. EDTA was used as positive control with the concentration of 1 mM. GE was used with the concentration of 1 μg/mL. All treatments were performed in triplicate and expressed as mean ± SD (n = 3). Significantly different between different groups and control are showed with *.
Figure 4
Figure 4
Effect of Gracilaria sp. extracts on ACE. Hippuryl-histidyl-leucine (HHL) was used as a substrate, and hippuric acid (HA) was measured at OD228. Captopril was used as positive control with the concentration of 10 μg/mL. All treatments were performed in triplicate and expressed as mean ± SD (n = 3). Different letters are show significantly different between groups.
Figure 5
Figure 5
Cytotoxicity test of Gracilaria sp. extracts in human hepatic HepG2 cells. Data are expressed as mean ± SD (n = 3).
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