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Synergistic Effect of Lithocholic Acid with Gentamicin against Gram-Positive Bacteria but Not against Gram-Negative Bacteria
oleh: Hongfa Lv, Lianping Wang, Shuang Liu, Wei Hu, Jianfeng Wang, Xuming Deng, Jinying Gao
Format: | Article |
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Diterbitkan: | MDPI AG 2022-04-01 |
Deskripsi
<i>Listeria monocytogenes</i> (<i>L. monocytogenes</i>) is an important Gram-positive food-borne pathogen that severely threatens public health. A checkerboard microdilution method was performed to evaluate the synergistic effect of lithocholic acid (LCA) with Gentamicin (Genta) against <i>L. monocytogenes</i>. BacLight LIVE/DEAD staining, scanning electron microscopy and biofilm inhibition assays were further used to explore the bactericidal effect and antibiofilm effect of this combination on <i>L. monocytogenes</i>. Additionally, the synergistic effects of LCA derivatives with Genta were also evaluated against <i>L. monocytogenes</i>, <i>S.</i><i>aureus</i> and <i>S. suis.</i> The results indicated that a synergistic bactericidal effect was observed for the combined therapy of LCA at the concentration without affecting bacteria viability, with Genta. Additionally, LCA in combination with Genta had a synergistic effect against Gram-positive bacteria (<i>L. monocytogenes</i>, <i>S</i><i>. aureus</i> and <i>S</i><i>. suis</i>) but not against Gram-negative bacteria (<i>E</i><i>. coli</i>, <i>A</i><i>. baumannii</i> and <i>Salmonella</i>). BacLight LIVE/DEAD staining and scanning electron microscopy analysis revealed that the combination of LCA with Genta caused <i>L. monocytogenes</i> membrane injury, leading to bacteria death. We found that 8 μg/mL LCA treatment effectively improved the ability of Genta to eradicate <i>L. monocytogenes</i> biofilms. In addition, we found that chenodeoxycholic acid, as a cholic acid derivative, also improved the bactericidal effect of Genta against Gram-positive bacteria. Our results indicate that LCA represents a broad-spectrum adjuvant with Genta for infection caused by <i>L. monocytogenes</i> and other Gram-positive pathogens.