Dual mode of action of Bac7, a proline-rich antibacterial peptide

Podda, Elena; Benincasa, Monica; Pacor, Sabrina; Micali, Fulvio; Mattiuzzo, Maura; Gennaro, Renato; Scocchi, Marco

doi:10.1016/j.bbagen.2006.09.006

Cited by 116 publications

(148 citation statements)

References 44 publications

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“…Bac7(1-35) and other PR-AMPs have also shown membranolytic activity in E. coli and S. Typhimurium, but only at much higher concentrations than their MIC values (16-to 64-fold); however, lytic effects due to PR-AMPs occur over longer times than those observed by most AMPs with lytic activity (30). For this reason, membrane damage has been described as a secondary effect at killing concentrations (30). No other species have been studied in details in relation to the killing mechanism.…”

Section: Mode Of Action Of Bac7(1-35) Against P Aeruginosamentioning

confidence: 99%

“…The flow cytometric assays were performed with a Cytomics FC 500 instrument (Beckman-Coulter, Inc., Fullerton, CA), as described previously (14,22). Integrity of bacterial cell membrane was assessed by measuring the propidium iodide (PI) uptake by flow cytometry, as previously described (30). Briefly, mid-log-phase bacterial cultures, diluted at 1 ϫ 10 6 CFU/ml in MHB, were incubated at 37°C for different times with increasing concentrations of Bac7 .…”

Section: Methodsmentioning

confidence: 99%

“…PR-AMPs cross the plasma membrane, exploiting the inner membrane protein SbmA (23,29), and enter the cytoplasm, where they inhibit vital functions such as protein synthesis (12). Bac7(1-35) and other PR-AMPs have also shown membranolytic activity in E. coli and S. Typhimurium, but only at much higher concentrations than their MIC values (16-to 64-fold); however, lytic effects due to PR-AMPs occur over longer times than those observed by most AMPs with lytic activity (30). For this reason, membrane damage has been described as a secondary effect at killing concentrations (30).…”

Section: Mode Of Action Of Bac7(1-35) Against P Aeruginosamentioning

confidence: 99%

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The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

Runti

Benincasa

Giuffrida

et al. 2017

Antimicrob Agents Chemother

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Pseudomonas aeruginosa infections represent a serious threat to worldwide health. Proline-rich antimicrobial peptides (PR-AMPs), a particular group of peptide antibiotics, have demonstrated in vitro activity against P. aeruginosa strains. Here we show that the mammalian PR-AMP Bac7(1-35) is active against some multidrug-resistant cystic fibrosis isolates of P. aeruginosa. By confocal microscopy and cytometric analyses, we investigated the mechanism of killing against P. aeruginosa strain PAO1 and three selected isolates, and we observed that the peptide inactivated the target cells by disrupting their cellular membranes. This effect is deeply different from that previously described for PR-AMPs in Escherichia coli and Salmonella enterica serovar Typhimurium, where these peptides act intracellularly after having been internalized by means of the transporter SbmA without membranolytic effects. The heterologous expression of SbmA in PAO1 cells enhanced the internalization of Bac7(1-35) into the cytoplasm, making the bacteria more susceptible to the peptide but at the same time more resistant to the membrane lysis, similarly to what occurs in E. coli. The results evidenced a new mechanism of action for PRAMPs and indicate that Bac7 has multiple and variable modes of action that depend on the characteristics of the different target species and the possibility to be internalized by bacterial transporters. This feature broadens the spectrum of activity of the peptide and makes the development of peptide-resistant bacteria a more difficult process.

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Section: Mode Of Action Of Bac7(1-35) Against P Aeruginosamentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Mode Of Action Of Bac7(1-35) Against P Aeruginosamentioning

confidence: 99%

See 1 more Smart Citation

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

Runti

Benincasa

Giuffrida

et al. 2017

Antimicrob Agents Chemother

Self Cite

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“…Resistant to proteases . Not cytotoxic on mammalian cells (Vooturi and Firestine 2010) therefore, all D-enantiomers are equally active, giving AMPs a broad action spectrum (Podda et al 2006). The mechanisms of action of AMPs are divided into pore and non-pore models (Wimley and Hristova 2011).…”

Section: Virusesmentioning

confidence: 99%

New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches

2012

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Antimicrobial peptides (AMPs) have a broad spectrum of activity and unspecific mechanisms of action. Therefore, they are seen as valid alternatives to overcome clinically relevant biofilms and reduce the chance of acquired resistance. This paper reviews AMPs and anti-biofilm AMP-based strategies and discusses ongoing and future work. Recent studies report successful AMP-based prophylactic and therapeutic strategies, several databases catalogue AMP information and analysis tools, and novel bioinformatics tools are supporting AMP discovery and design. However, most AMP studies are performed with planktonic cultures, and most studies on sessile cells test AMPs on growing rather than mature biofilms. Promising preliminary synergistic studies have to be consubstantiated and the study of functionalized coatings with AMPs must be further explored. Standardized operating protocols, to enforce the repeatability and reproducibility of AMP anti-biofilm tests, and automated means of screening and processing the ever-expanding literature are still missing.

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“…In the case of latter, the peptides penetrate all the way through the membrane and then inhibit various intracellular functions, including cell wall, nucleic acid and protein synthesis (9). Interestingly, recent findings suggest that the bactericidal effects of some antibacterial peptides involve a dual mode of action: membrane disruption coupled to secondary intracellular targeting (10,11). The antibacterial peptide bactenecin, which is expressed by bovine neutrophils, is a β-hairpin monomer that contains four arginine residues and one intramolecular disulfide bond, and is more potent against Gram-negative than Gram-positive bacteria (12,13).…”

Section: Introductionmentioning

confidence: 99%

Different modes of antibiotic action of homodimeric and monomeric bactenecin, a cathelicidin-derived antibacterial peptide

Lee

Yang²,

Kim³

et al. 2009

BMB Reports

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The bactenecin is an antibacterial peptide with an intramolecular disulfide bond. We recently found that homodimeric bactenecin exhibits more potent antibacterial activity than the monomeric form and retains its activity at physiological conditions. Here we assess the difference in the modes of antibiotic action of homodimeric and monomeric bactenecins. Both monomeric and dimeric bactenecins almost completely killed both Staphylococcus aureus and E. coli within 10-30 min at concentrations of 8-16 μM. However, exposure to liposomes elicited an increase in the fluorescence quantum yield from a tryptophan-containing monomeric analog, while the homodimeric analog showed a significant reduction in fluorescence intensity. Moreover, unlike the monomer, the homodimer displayed apparent membrane-lytic activity enabling release of various sized dyes from liposomes, and rapidly and fully depolarized the S. aureus membrane. Together, our results suggest that homodimeric bactenecin forms pores in the bacterial membrane, while monomeric one penetrates through the membrane to target intracellular molecules/ organelles. [BMB reports 2009; 42(9): 586-592]

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Dual mode of action of Bac7, a proline-rich antibacterial peptide

Cited by 116 publications

References 44 publications

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches

Different modes of antibiotic action of homodimeric and monomeric bactenecin, a cathelicidin-derived antibacterial peptide

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