Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo
The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments. It has been reported that niclosamide (NIC) can restore the sensitivity of Gram-negative bacteria to colistin (COL). However, NIC is practic...
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Elsevier
2024-12-01
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| Series: | Poultry Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0032579124010708 |
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| author | Junkai Zhang Qingqing Miao Xiaoyuan Ma Dandan He Yushan Pan Li Yuan Yajun Zhai Gongzheng Hu |
| author_facet | Junkai Zhang Qingqing Miao Xiaoyuan Ma Dandan He Yushan Pan Li Yuan Yajun Zhai Gongzheng Hu |
| author_sort | Junkai Zhang |
| collection | DOAJ |
| description | The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments. It has been reported that niclosamide (NIC) can restore the sensitivity of Gram-negative bacteria to colistin (COL). However, NIC is practically insoluble in water and sparingly soluble in organic solvents, leading to limited therapeutic applications. This study aims to prepare a COL-NIC effervescent dry suspension (CNEDS) and evaluate its antibacterial effect against COL-resistant Salmonella both in vitro and in broiler chickens. With the sedimentation volume ratio as an index, suitable suspending agent, wetting agent, filler and effervescent agent were screened through a single-factor method. The preparation conditions were optimized using the Box-Behnken response surface method to obtain the formulation for CNEDS. The quality evaluation results showed that the successfully prepared CNEDS had a sedimentation volume ratio of 0.99, a drying weight loss of 1.3%, and a re-dispersion capability of 1-2 times, all of which met pharmacopoeial requirements. In terms of pharmacological evaluation, we first demonstrated that CNEDS substantially restored COL sensitivity against COL-resistant bacteria. Subsequently, time-killing analysis, scanning electron microscopy (SEM) and live/dead assays confirmed the antibacterial activity of CNEDS against COL-resistant bacteria. Finally, a Salmonella infection model in broiler chickens was established to further assess the therapeutic effect of CNEDS in vivo. CNEDS improved the survival rate of broiler chickens, reduced the bacterial burden on organs. These findings suggest that CNEDS effectively overcome COL resistance, indicating its potential for the treatment of COL-resistant bacterial infections in broiler chickens. |
| format | Article |
| id | doaj-art-47db838e4cc54e28aaee5432786bfcfd |
| institution | Kabale University |
| issn | 0032-5791 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Poultry Science |
| spelling | doaj-art-47db838e4cc54e28aaee5432786bfcfd2024-12-14T06:29:24ZengElsevierPoultry Science0032-57912024-12-0110312104492Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivoJunkai Zhang0Qingqing Miao1Xiaoyuan Ma2Dandan He3Yushan Pan4Li Yuan5Yajun Zhai6Gongzheng Hu7College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR China; Key Laboratory of Quality and Safety Control of Poultry Products (Zhengzhou), Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, 450046, PR ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR China; Key Laboratory of Quality and Safety Control of Poultry Products (Zhengzhou), Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, 450046, PR ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR China; Key Laboratory of Quality and Safety Control of Poultry Products (Zhengzhou), Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, 450046, PR ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR China; Key Laboratory of Quality and Safety Control of Poultry Products (Zhengzhou), Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, 450046, PR ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR China; Key Laboratory of Quality and Safety Control of Poultry Products (Zhengzhou), Ministry of Agriculture and Rural Affairs, Zhengzhou, 450046, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou, 450046, PR China; Corresponding author.The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments. It has been reported that niclosamide (NIC) can restore the sensitivity of Gram-negative bacteria to colistin (COL). However, NIC is practically insoluble in water and sparingly soluble in organic solvents, leading to limited therapeutic applications. This study aims to prepare a COL-NIC effervescent dry suspension (CNEDS) and evaluate its antibacterial effect against COL-resistant Salmonella both in vitro and in broiler chickens. With the sedimentation volume ratio as an index, suitable suspending agent, wetting agent, filler and effervescent agent were screened through a single-factor method. The preparation conditions were optimized using the Box-Behnken response surface method to obtain the formulation for CNEDS. The quality evaluation results showed that the successfully prepared CNEDS had a sedimentation volume ratio of 0.99, a drying weight loss of 1.3%, and a re-dispersion capability of 1-2 times, all of which met pharmacopoeial requirements. In terms of pharmacological evaluation, we first demonstrated that CNEDS substantially restored COL sensitivity against COL-resistant bacteria. Subsequently, time-killing analysis, scanning electron microscopy (SEM) and live/dead assays confirmed the antibacterial activity of CNEDS against COL-resistant bacteria. Finally, a Salmonella infection model in broiler chickens was established to further assess the therapeutic effect of CNEDS in vivo. CNEDS improved the survival rate of broiler chickens, reduced the bacterial burden on organs. These findings suggest that CNEDS effectively overcome COL resistance, indicating its potential for the treatment of COL-resistant bacterial infections in broiler chickens.http://www.sciencedirect.com/science/article/pii/S0032579124010708ColistinNiclosamideResistanceDry suspensionSalmonella |
| spellingShingle | Junkai Zhang Qingqing Miao Xiaoyuan Ma Dandan He Yushan Pan Li Yuan Yajun Zhai Gongzheng Hu Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo Poultry Science Colistin Niclosamide Resistance Dry suspension Salmonella |
| title | Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo |
| title_full | Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo |
| title_fullStr | Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo |
| title_full_unstemmed | Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo |
| title_short | Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo |
| title_sort | colistin niclosamide effervescent dry suspension combats colistin resistant salmonella in vitro and in vivo |
| topic | Colistin Niclosamide Resistance Dry suspension Salmonella |
| url | http://www.sciencedirect.com/science/article/pii/S0032579124010708 |
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