Gramicidin S and polymyxins: the revival of cationic cyclic peptide antibiotics

Mogi, Tatsushi; Kita, Kiyoshi

doi:10.1007/s00018-009-0129-9

Cited by 111 publications

(86 citation statements)

References 61 publications

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“…A ratio of Ͼ1 indicates transcriptional activation due to the presence of a specific compound. (28,61,71). Under the employed growth condition, the most distinct resistance phenotypes for the wild-type strain in comparison to the ⌬PA0920 strain were observed in the presence of ampicillin, oxacillin, cefsulodin, daptomycin, protamine sulfate, poly-L-lysine, and polymyxin E (compare structures denoted in Fig.…”

Section: Resultsmentioning

confidence: 99%

Resistance Phenotypes Mediated by Aminoacyl-Phosphatidylglycerol Synthases

et al. 2012

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The specific aminoacylation of the phospholipid phosphatidylglycerol (PG) with alanine or with lysine catalyzed by aminoacylphosphatidylglycerol synthases (aaPGS) was shown to render various organisms less susceptible to antibacterial agents. This study makes use of Pseudomonas aeruginosa chimeric mutant strains producing lysyl-phosphatidylglycerol (L-PG) instead of the naturally occurring alanyl-phosphatidylglycerol (A-PG) to study the resulting impact on bacterial resistance. Consequences of such artificial phospholipid composition were studied in the presence of an overall of seven antimicrobials (␤-lactams, a lipopeptide antibiotic, cationic antimicrobial peptides [CAMPs]) to quantitatively assess the effect of A-PG substitution (with L-PG, L-PG and A-PG, increased A-PG levels). For the employed Gram-negative P. aeruginosa model system, an exclusive charge repulsion mechanism does not explain the attenuated antimicrobial susceptibility due to PG modification. Additionally, the specificity of nine orthologous aaPGS enzymes was experimentally determined. The newly characterized protein sequences allowed for the establishment of a significant group of A-PG synthase sequences which were bioinformatically compared to the related group of L-PG synthesizing enzymes. The analysis revealed a diverse origin for the evolution of A-PG and L-PG synthases, as the specificity of an individual enzyme is not reflected in terms of a characteristic sequence motif. This finding is relevant for future development of potential aaPGS inhibitors.

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Section: Resultsmentioning

confidence: 99%

Resistance Phenotypes Mediated by Aminoacyl-Phosphatidylglycerol Synthases

et al. 2012

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“…Third, when used as an antibiotic drug clinically, the immunostimulatory potential might contribute to drug toxicity. In fact, polymyxin B's, gramicidin's, tyrothricin's, and neomycin's toxicity profiles do not recommend systemic treatment, and all four drugs are in topical use only (18)(19)(20). The cyclic polypeptides and aminoglycosides have different toxicity profiles; therefore, it is unlikely that drug toxicity is solely mediated by IL-1b secretion.…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: Cyclic Polypeptide and Aminoglycoside Antibiotics Trigger IL-1β Secretion by Activating the NLRP3 Inflammasome

Allam

Darisipudi²,

Rupanagudi³

et al. 2011

The Journal of Immunology

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Clinical use of antibiotics is based on their capacity to inhibit bacterial growth via bacteriostatic or bacteriocidal effects. In this article, we show that the aminoglycoside antibiotic neomycin, the cyclic lipopeptide antibiotic polymyxin B, and the cyclic peptide antibiotics gramicidin and tyrothricin can induce IL-1β secretion in bone marrow dendritic cells and macrophages. LPS priming was required to trigger the transcription and translation of pro–IL-1β but was independent of TNFR or IL-1R signaling. All four antibiotics required the NLRP3 inflammasome, the adaptor ASC, and caspase-1 activation to secrete IL-1β, a process that depended on potassium efflux but was independent of P2X7 receptor. All four antibiotics induced neutrophil influx into the peritoneal cavity of mice, which required NLRP3 only in the case of polymyxin B. Together, certain antibiotics have the potential to directly activate innate immunity of the host.

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“…Used to study organization, dynamics, and function of membrane-spanning channels (Yala et al 2011) . Linear gramicidins enter lipid membranes forming a dimer channel that conducts a cation flow (Mogi and Kita 2009;Yala et al 2011) (continued) . C-terminal alcohol (Sang and Blecha 2008;Duclohier 2010) .…”

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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Gramicidin S and polymyxins: the revival of cationic cyclic peptide antibiotics

Cited by 111 publications

References 61 publications

Resistance Phenotypes Mediated by Aminoacyl-Phosphatidylglycerol Synthases

Resistance Phenotypes Mediated by Aminoacyl-Phosphatidylglycerol Synthases

Cutting Edge: Cyclic Polypeptide and Aminoglycoside Antibiotics Trigger IL-1β Secretion by Activating the NLRP3 Inflammasome

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

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