The Journal of antimicrobial chemotherapy · 2022
Synergy of outer membrane disruptor SLAP-S25 with hydrophobic antibiotics against Gram-negative pathogens.
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Yang Zhiqiang, Song Meirong, Li Xiaoyu, Zhang Qi, Shen Jianzhong, Zhu Kui
Аннотация
OBJECTIVES: An effective strategy for combating MDR Gram-negative pathogens can greatly reduce the cost and shorten the antibiotic development progress. Here, we investigated the synergistic activity of outer membrane disruptor SLAP-S25 in combination with hydrophobic antibiotics (LogP > 2, including novobiocin, erythromycin, clindamycin and rifampicin) against MDR Gram-negative pathogens.
METHODS: Five representative Gram-negative bacteria were selected as model strains to analyse the synergistic combination of SLAP-S25 and hydrophobic antibiotics. Carbapenem-resistant hypervirulent Klebsiella pneumoniae CRHvKP4 was used to investigate the synergistic mechanism. The in vivo synergistically therapeutic activity of SLAP-S25 and hydrophobic antibiotics was measured in the mouse peritonitis/sepsis model infected with K. pneumoniae CRHvKP4.
RESULTS: SLAP-S25 disrupted the outer membrane by removing LPS from Gram-negative bacteria, facilitating the entry of hydrophobic antibiotics to kill MDR Gram-negative pathogens. Moreover, the combination of SLAP-S25 and rifampicin exhibited promising therapeutic effects in the mouse infection model infected with K. pneumoniae CRHvKP4.
CONCLUSIONS: Our findings provide a potential therapeutic strategy to combine SLAP-S25 with hydrophobic antibiotics for combating MDR Gram-negative pathogens.
METHODS: Five representative Gram-negative bacteria were selected as model strains to analyse the synergistic combination of SLAP-S25 and hydrophobic antibiotics. Carbapenem-resistant hypervirulent Klebsiella pneumoniae CRHvKP4 was used to investigate the synergistic mechanism. The in vivo synergistically therapeutic activity of SLAP-S25 and hydrophobic antibiotics was measured in the mouse peritonitis/sepsis model infected with K. pneumoniae CRHvKP4.
RESULTS: SLAP-S25 disrupted the outer membrane by removing LPS from Gram-negative bacteria, facilitating the entry of hydrophobic antibiotics to kill MDR Gram-negative pathogens. Moreover, the combination of SLAP-S25 and rifampicin exhibited promising therapeutic effects in the mouse infection model infected with K. pneumoniae CRHvKP4.
CONCLUSIONS: Our findings provide a potential therapeutic strategy to combine SLAP-S25 with hydrophobic antibiotics for combating MDR Gram-negative pathogens.