Year: 2017
Type: article
Abstract: Antimicrobial peptides (AMPs) are thought to kill bacterial cells by permeabilizing their membranes.However, some antimicrobial peptides inhibit E. coli growth more efficiently in aerobic than in anaerobic conditions.In the attack of the human cathelicidin LL-37 on E. coli, real-time, single-cell fluorescence imaging reveals the timing of membrane permeabilization and the onset of oxidative stress.For cells growing aerobically, a CellROX Green assay indicates that LL-37 induces rapid formation of oxidative species after entry into the periplasm, but before permeabilization of the cytoplasmic membrane (CM).A cytoplasmic Amplex Red assay signals a subsequent burst of oxidative species, most likely hydrogen peroxide, shortly after permeabilization of the CM.These signals are much stronger in the presence of oxygen, a functional electron transport chain, and a large proton motive force (PMF).They are much weaker in cells growing anaerobically, by either fermentation or anaerobic respiration.In aerobic growth, the oxidative signals are attenuated in a cytochrome oxidase-bd deletion mutant, but not in a -bo 3 deletion mutant, suggesting a specific effect of LL-37 on the electron transport chain.The AMPs melittin and LL-37 induce strong oxidative signals and exhibit O 2 -sensitive MICs, while the AMPs indolicidin and cecropin A do not.These results suggest that AMP activity in different tissues may be tuned according to the local oxygen level.This may be significant for control of opportunistic pathogens while enabling growth of commensal bacteria. Author summaryAntimicrobial peptides play a significant role in the innate immune response of plants and animals, including humans.While it is well known that AMPs can permeabilize bacterial cell membranes, a growing body of evidence indicates that they cause a variety of additional deleterious effects.Here we use single-cell imaging methods to study the induction of oxidative stress in live E. coli by several natural cationic AMPs, including the human cathelicidin LL-37.Strong fluorescence signals indicative of oxidative stress correlate with smaller minimum inhibitory concentrations (MICs) in aerobic vs anaerobic growth conditions.A detailed mechanistic study suggests that LL-37 disrupts the proper
Source: PLoS Pathogens
Authors: Heejun Choi, Zhilin Yang, James C. Weisshaar
Institution: University of Wisconsin–Madison
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
OpenAlex ID: W2731570178