Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance

被引：246

作者：

Spohn, Reka ^{[1
]}

Daruka, Lejla ^{[1
,2
]}

Lazar, Viktoria ^{[1
,8
]}

Martins, Ana ^{[1
]}

Vidovics, Fanni ^{[1
]}

Grezal, Gabor ^{[1
,3
]}

Mehi, Orsolya ^{[1
]}

Kintses, Balint ^{[1
,4
]}

Szamel, Monika ^{[1
,2
]}

Jangir, Pramod K. ^{[1
,2
]}

Csorgo, Balint ^{[1
,9
]}

Gyorkei, Adam ^{[1
,3
]}

Bodi, Zoltan ^{[1
]}

Farago, Aniko ^{[2
,4
]}

Bodai, Laszlo ^{[4
]}

Foldesi, Imre ^{[5
]}

Kata, Diana ^{[5
]}

Maroti, Gergely ^{[6
]}

Pap, Bernadett ^{[6
]}

Wirth, Roland ^{[7
]}

Papp, Balazs ^{[1
,3
]}

Pal, Csaba ^{[1
]}

机构：

[1] Biol Res Ctr, Inst Biochem, Synthet & Syst Biol Unit, Szeged, Hungary

[2] Univ Szeged, Fac Sci & Informat, Doctoral Sch Biol, Szeged, Hungary

[3] HCEMM BRC Metab Syst Biol Lab, Szeged, Hungary

[4] Univ Szeged, Dept Biochem & Mol Biol, Szeged, Hungary

[5] Univ Szeged, Dept Lab Med, Szeged, Hungary

[6] Hungarian Acad Sci, Biol Res Ctr, Inst Plant Biol, Szeged, Hungary

[7] Univ Szeged, Dept Biotechnol, Szeged, Hungary

[8] Technion Israel Inst Technol, Fac Biol, Haifa, Israel

[9] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国惠康基金; 欧洲研究理事会;

关键词：

HOST-DEFENSE PEPTIDES; ANTIBIOTIC-RESISTANCE; GENE AMPLIFICATION; SOIL BACTERIA; MECHANISMS; PROTAMINE; RESERVOIR; DATABASE; MUTD5;

D O I：

10.1038/s41467-019-12364-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Antimicrobial peptides (AMPs) are promising antimicrobials, however, the potential of bacterial resistance is a major concern. Here we systematically study the evolution of resistance to 14 chemically diverse AMPs and 12 antibiotics in Escherichia coli. Our work indicates that evolution of resistance against certain AMPs, such as tachyplesin II and cecropin P1, is limited. Resistance level provided by point mutations and gene amplification is very low and antibiotic-resistant bacteria display no cross-resistance to these AMPs. Moreover, genomic fragments derived from a wide range of soil bacteria confer no detectable resistance against these AMPs when introduced into native host bacteria on plasmids. We have found that simple physicochemical features dictate bacterial propensity to evolve resistance against AMPs. Our work could serve as a promising source for the development of new AMP-based therapeutics less prone to resistance, a feature necessary to avoid any possible interference with our innate immune system.

引用

页数：13

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