
細菌集団内の一部の細菌は、薬剤排出ポンプの発現増加、外膜小胞の分泌、膜の変化などの応答を示すことで、抗菌ペプチドの蓄積を抑え、表現型耐性を示す。


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

細菌集団内の異質な薬剤排出ポンプ発現が抗菌ペプチドに対する表現型耐性の基盤となる