Apolipoprotein E‐derived antimicrobial peptide analogues with altered membrane affinity and increased potency and breadth of activity

Kelly, Bridie A.; Neil, Stuart J. D.; McKnight, Áine; Santos, Joana; Sinnis, Photini; Jack, Edward R.; Middleton, David A.; Dobson, Curtis B.

doi:10.1111/j.1742-4658.2007.05981.x

Cited by 27 publications

(41 citation statements)

References 50 publications

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“…The ApoEdpL-W antimicrobial peptide was previously shown to inhibit growth of both P. aeruginosa and S. aureus when added at micromolar concentrations on planktonic cultures (26). We tested the activity of ApoEdpL-W on planktonic and biofilm E. coli K-12 bacteria by using either strain MG1655 or its biofilm-forming isogenic derivative, MG1655 F= (37).…”

Section: Resultsmentioning

confidence: 99%

“…In this study, we investigated resistance mechanisms potentially induced by a new antimicrobial peptide derived from human apolipoprotein E, ApoEdpL-W. ApoEdpL-W is an aromatic-substituted peptide previously reported to be active against P. aeruginosa and S. aureus pathogens and to possibly interact with membranes (26). We showed that E. coli exposure to ApoEdpL-W induces Rcs, Cpx, and E pathways, three regulatory pathways known to sense envelope stress.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a new family of antimicrobial peptides, derived from human apolipoprotein E (ApoE) and acting via perturbation of the membrane lipid bilayer, was described (26,27). The original ApoEdp peptide (sequence, LRKLRKRLLLRKLRKRLL) showed direct, broad anti-infective activity against bacteria and viruses (27).…”

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confidence: 99%

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Induction of the Cpx Envelope Stress Pathway Contributes to Escherichia coli Tolerance to Antimicrobial Peptides

Audrain

Ferrières

Zaïri

et al. 2013

Appl Environ Microbiol

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e Antimicrobial peptides produced by multicellular organisms as part of their innate system of defense against microorganisms are currently considered potential alternatives to conventional antibiotics in case of infection by multiresistant bacteria. However, while the mode of action of antimicrobial peptides is relatively well described, resistance mechanisms potentially induced or selected by these peptides are still poorly understood. In this work, we studied the mechanisms of action and resistance potentially induced by ApoEdpL-W, a new antimicrobial peptide derived from human apolipoprotein E. Investigation of the genetic response of Escherichia coli upon exposure to sublethal concentrations of ApoEdpL-W revealed that this antimicrobial peptide triggers activation of RcsCDB, CpxAR, and E envelope stress pathways. This genetic response is not restricted to ApoEdpL-W, since several other antimicrobial peptides, including polymyxin B, melittin, LL-37, and modified S 4 dermaseptin, also activate several E. coli envelope stress pathways. Finally, we demonstrate that induction of the CpxAR two-component system directly contributes to E. coli tolerance toward ApoEdpL-W, polymyxin B, and melittin. These results therefore show that E. coli senses and responds to different antimicrobial peptides by activation of the CpxAR pathway. While this study further extends the understanding of the array of peptide-induced stress signaling systems, it also provides insight into the contribution of Cpx envelope stress pathway to E. coli tolerance to antimicrobial peptides.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Induction of the Cpx Envelope Stress Pathway Contributes to Escherichia coli Tolerance to Antimicrobial Peptides

Audrain

Ferrières

Zaïri

et al. 2013

Appl Environ Microbiol

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“…Kelly et al (35) recently described a series of peptides with low hemolytic activity and a broad spectrum of antimicrobial and antiviral activities. These peptides were derived from the receptor-binding region of human apolipoprotein E (ApoE), which has been shown to possess anti-infective properties (13).…”

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confidence: 99%

Endocytosis-Mediated Vacuolar Accumulation of the Human ApoE Apolipoprotein-Derived ApoEdpL-W Antimicrobial Peptide Contributes to Its Antifungal Activity in Candida albicans

Rossignol

Kelly

Dobson

et al. 2011

Antimicrob Agents Chemother

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“…In addition, the lipidome composition of HCV particles has been shown to resemble that of VLDLs and LDLs (66), suggesting that CAMP is able to interact with HCV particles. Moreover, some AMPs are designed based on apolipoprotein sequences (67)(68)(69). This apparent cross talk between CAMP and apolipoproteins suggests that amphipathic ␣-helices from both proteins probably share the ability to bind to the same types of lipid membranes and induce similar curvature effects (70,71).…”

Section: Discussionmentioning

confidence: 99%

Human Cathelicidin Compensates for the Role of Apolipoproteins in Hepatitis C Virus Infectious Particle Formation

Puig-Basagoiti

Fukuhara

Tamura

et al. 2016

J Virol

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Exchangeable apolipoproteins (ApoA, -C, and -E) have been shown to redundantly participate in the formation of infectious hepatitis C virus (HCV) particles during the assembly process, although their precise role in the viral life cycle is not well understood. Recently, it was shown that the exogenous expression of only short sequences containing amphipathic ␣-helices from various apolipoproteins is sufficient to restore the formation of infectious HCV particles in ApoB and ApoE double-gene-knockout Huh7 (BE-KO) cells. In this study, through the expression of a small library of human secretory proteins containing amphipathic ␣-helix structures, we identified the human cathelicidin antimicrobial peptide (CAMP), the only known member of the cathelicidin family of antimicrobial peptides (AMPs) in humans and expressed mainly in bone marrow and leukocytes. We showed that CAMP is able to rescue HCV infectious particle formation in BE-KO cells. In addition, we revealed that the LL-37 domain in CAMP containing amphipathic ␣-helices is crucial for the compensation of infectivity in BE-KO cells, and the expression of CAMP in nonhepatic 293T cells expressing claudin 1 and microRNA miR-122 confers complete propagation of HCV. These results suggest the possibility of extrahepatic propagation of HCV in cells with low-level or no expression of apolipoproteins but expressing secretory proteins containing amphipathic ␣-helices such as CAMP. IMPORTANCEVarious exchangeable apolipoproteins play a pivotal role in the formation of infectious HCV during the assembly of viral particles, and amphipathic ␣-helix motifs in the apolipoproteins have been shown to be a key factor. To the best of our knowledge, we have identified for the first time the human cathelicidin CAMP as a cellular protein that can compensate for the role of apolipoproteins in the life cycle of HCV. We have also identified the domain in CAMP that contains amphipathic ␣-helices crucial for compensation and show that the expression of CAMP in nonhepatic cells expressing claudin 1 and miR-122 confers complete propagation of HCV. We speculate that low levels of HCV propagation might be possible in extrahepatic tissues expressing secretory proteins containing amphipathic ␣-helices without the expression of apolipoproteins. According to recent estimates, more than 160 million people worldwide are chronically infected with hepatitis C virus (HCV) (1), which causes liver-related pathologies that can result in life-threatening diseases such as cirrhosis and hepatocellular carcinoma (2). Chronic HCV infection is also associated with several extrahepatic manifestations, including immunological disorders such as cryoglobulinemia and B-cell non-Hodgkin lymphoma (3). A vaccine is not yet available, but recent advances in antiviral treatment, improving upon what was for many years the standard therapy of pegylated interferon alpha plus ribavirin, now include several direct-acting antivirals (DAAs) that have increased the rate of sustained virological response (SVR) up to 80 ...

show abstract

Apolipoprotein E‐derived antimicrobial peptide analogues with altered membrane affinity and increased potency and breadth of activity

Cited by 27 publications

References 50 publications

Induction of the Cpx Envelope Stress Pathway Contributes to Escherichia coli Tolerance to Antimicrobial Peptides

Induction of the Cpx Envelope Stress Pathway Contributes to Escherichia coli Tolerance to Antimicrobial Peptides

Endocytosis-Mediated Vacuolar Accumulation of the Human ApoE Apolipoprotein-Derived ApoEdpL-W Antimicrobial Peptide Contributes to Its Antifungal Activity in Candida albicans

Human Cathelicidin Compensates for the Role of Apolipoproteins in Hepatitis C Virus Infectious Particle Formation

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