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In recent decades, the extensive and inappropriate use of antibiotics has led to the emergence of antibiotic-resistant bacteria, posing a serious threat to human health. Phage therapy has emerged as a promising approach for preventing and treating infections caused by drug-resistant bacteria, garnering considerable research interest. However, the rapid development of phage-resistant bacterial strains complicates the effectiveness of phage therapy. The phage steering strategy holds promise for addressing this challenge. Objective To isolate virulent phages specific to Salmonella that are suitable for phage steering therapy. Methods Specific virulent phages for Salmonella S503 were isolated and purified from wastewater samples collected from a wet market via the double agar overlay method. Their fundamental biological characteristics, antibacterial efficacy, genomic information, and in vitro biological safety were analyzed. Phage-resistant strains were generated through co-culturing Salmonella S503 with the phages. Subsequently, growth curve analysis, bacterial virulence testing, and antibiotic sensitivity assays were employed to systematically compare the characteristics of the wild-type strain and its phage-resistant counterpart. Results The isolated Salmonella phage was designated HK-1. This phage exhibited strong antibacterial properties, high stability, and confirmed biological safety in vitro. Compared with the wild-type strain Salmonella S503, the phage-resistant strain Salmonella S503-R displayed slow growth, significantly reduced virulence, and increased susceptibility to 11 different antibiotics. Furthermore, phage HK-1 demonstrated synergistic bactericidal effects when being combined with rifampicin, ampicillin, fosfomycin, and gentamicin. Notably, the combinations of HK-1 with ampicillin, fosfomycin, and gentamicin effectively inhibited the growth of Salmonella S503 within 24 h. Conclusion We successfully isolated a virulent phage from wastewater samples. This phage is suitable for phage steering therapy and offers potential for the prevention and treatment of antibiotic-resistant Salmonella.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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