
細菌群體中存在兩種表型亞群:一種能夠高度累積抗菌肽,另一種則能夠通過增強排出泵、膜脂質改變和分泌外膜囊泡來降低抗菌肽的累積,從而逃避抗菌肽的殺滅作用。


coremsg

Antimicrobial resistance threatens the viability of modern medical interventions. There is a dire need of developing novel approaches to counter resistance mechanisms employed by starved or slow-growing pathogens that are refractory to conventional antimicrobial therapies. Antimicrobial peptides have been advocated as potential therapeutic solutions due to low levels of genetic resistance observed in bacteria against these compounds. However, here we show that subpopulations of stationary phase Escherichia coli and Pseudomonas aeruginosa survive tachyplesin treatment without genetic mutations. These phenotypic variants induce efflux, outer membrane vesicles secretion and membrane modifications in response to tachyplesin exposure, sequestering the peptide in their membranes where it cannot exert its antimicrobial activity. We discovered that formation of these phenotypic variants could be prevented by administering tachyplesin in combination with sertraline, a clinically used antidepressant, suggesting a novel approach for combatting antimicrobial-refractory stationary phase bacteria.

### Competing Interest Statement

The authors have declared no competing interest.

Heterogeneous efflux pump expression underpins phenotypic resistance to antimicrobial peptides

大腸桿菌和綠膿桿菌中異質性的排出泵表達支撐了對抗菌肽的表型耐藥性