Interactions of plumbagin with five common antibiotics against Staphylococcus aureus in vitro

Songtao Bie; Qiuyue Mo; Chen Shi; Hui Yuan; Chunshuang Li; Tong Wu; Wenlong Li; Heshui Yu

doi:10.1371/journal.pone.0297493

Interactions of plumbagin with five common antibiotics against Staphylococcus aureus in vitro

PLoS One. 2024 Jan 26;19(1):e0297493. doi: 10.1371/journal.pone.0297493. eCollection 2024.

Authors

Songtao Bie^{1

2

3}, Qiuyue Mo^{1

3}, Chen Shi^{1

3}, Hui Yuan^{1

3}, Chunshuang Li^{1

3}, Tong Wu^{1

3}, Wenlong Li^{1

2

3}, Heshui Yu^{1

2

3}

Affiliations

¹ College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
² State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
³ Haihe Laboratory of Modern Chinese Medicine, Tianjin, China.

Abstract

Staphylococcus aureus is the main culprit, causing a variety of severe clinical infections. At the same time, clinics are also facing the severe situation of antibiotic resistance. Therefore, effective strategies to address this problem may include expanding the antimicrobial spectrum by exploring alternative sources of drugs or delaying the development of antibiotic resistance through combination therapy so that existing antibiotics can continue to be used. Plumbagin (PLU) is a phytochemical that exhibits antibacterial activity. In the present study, we investigated the in vitro antibacterial activity of PLU. We selected five antibiotics with different mechanisms and inhibitory activities against S. aureus to explore their interaction with the combination of PLU. The interaction of combinations was evaluated by the Bliss independent model and visualized through response surface analysis. PLU exhibited potent antibacterial activity, with half maximal inhibitory concentration (IC50) and minimum inhibitory concentration (MIC) values against S. aureus of 1.73 μg/mL and 4 μg/mL, respectively. Synergism was observed when PLU was combined with nitrofurantoin (NIT), ciprofloxacin (CPR), mecillinam (MEC), and chloramphenicol (CHL). The indifference of the trimethoprim (TMP)-PLU pairing was demonstrated across the entire dose-response matrix, but significant synergy was observed within a specific dose region. In addition, no antagonistic interactions were indicated. Overall, PLU is not only a promising antimicrobial agent but also has the potential to enhance the growth-inhibitory activity of some antibiotics against S. aureus, and the use of the interaction landscape, along with the dose-response matrix, for analyzing and quantifying combination results represents an improved approach to comprehending antibacterial combinations.

Copyright: © 2024 Bie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Infective Agents* / pharmacology
Drug Synergism
Humans
Methicillin-Resistant Staphylococcus aureus*
Microbial Sensitivity Tests
Naphthoquinones*
Staphylococcal Infections*
Staphylococcus aureus

Substances

Anti-Bacterial Agents
plumbagin
Anti-Infective Agents
Naphthoquinones

Grants and funding

Y W. Science and Technology Program of Tianjin (22ZYJDSS00100). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Y W. Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine (22HHZYSS00003).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. S B. Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D202002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.