Synergistic effects of ovine-derived cathelicidins and other antimicrobials against Escherichia coli O157:H7 and Staphylococcus aureus 1056 MRSA

Linden, D. S. van der; Short, David; Dittmann, Antje; Yu, Pak-Lam

doi:10.1007/s10529-009-0010-9

Cited by 25 publications

(20 citation statements)

References 9 publications

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“…This serum and cation sensitivity could mean that, in vivo, other antimicrobial mechanisms are needed to kill bacteria, and cathelicidins are instead required to reduce immune activation against the dead bacteria. Cathelicidins have been shown to act in synergy with other hostderived antimicrobial components, such as lysozyme and lactoferrin, which are stored in the same neutrophil granules as cathelicidins (13,58,59). Thus, although most cathelicidins have limited antimicrobial activity under cell culture conditions in vitro, their bactericidal activity during infections in vivo might be enhanced by acting in concert with other host-derived antimicrobial components.…”

Section: Discussionmentioning

confidence: 99%

Cathelicidins Inhibit Escherichia coli–Induced TLR2 and TLR4 Activation in a Viability-Dependent Manner

Coorens

Schneider

Groot

et al. 2017

The Journal of Immunology

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Activation of the immune system needs to be tightly regulated to provide protection against infections and, at the same time, to prevent excessive inflammation to limit collateral damage to the host. This tight regulation includes regulating the activation of TLRs, which are key players in the recognition of invading microbes. A group of short cationic antimicrobial peptides, called cathelicidins, have previously been shown to modulate TLR activation by synthetic or purified TLR ligands and may play an important role in the regulation of inflammation during infections. However, little is known about how these cathelicidins affect TLR activation in the context of complete and viable bacteria. In this article, we show that chicken cathelicidin-2 kills Escherichia coli in an immunogenically silent fashion. Our results show that chicken cathelicidin-2 kills E. coli by permeabilizing the bacterial inner membrane and subsequently binds the outer membrane-derived lipoproteins and LPS to inhibit TLR2 and TLR4 activation, respectively. In addition, other cathelicidins, including human, mouse, pig, and dog cathelicidins, which lack antimicrobial activity under cell culture conditions, only inhibit macrophage activation by nonviable E. coli. In total, this study shows that cathelicidins do not affect immune activation by viable bacteria and only inhibit inflammation when bacterial viability is lost. Therefore, cathelicidins provide a novel mechanism by which the immune system can discriminate between viable and nonviable Gramnegative bacteria to tune the immune response, thereby limiting collateral damage to the host and the risk for sepsis.

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Section: Discussionmentioning

confidence: 99%

Cathelicidins Inhibit Escherichia coli–Induced TLR2 and TLR4 Activation in a Viability-Dependent Manner

Coorens

Schneider

Groot

et al. 2017

The Journal of Immunology

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“…Lysozyme is a good candidate for hybridization due to the reported synergism between lysozyme and other antimicrobial components including cecropins, defensins, cathelicidins, etc [23,[37][38][39]. In the present study, novel hybrid protein combining PI with hLY was designed.…”

Section: Dissussionmentioning

confidence: 99%

Characterization of bioactive recombinant antimicrobial peptide parasin I fused with human lysozyme expressed in the yeast Pichia pastoris system

Zhao

Tang

Cao

et al. 2015

Enzyme and Microbial Technology

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“…As described previously, SMAP-29 when expressed as a fusion peptide with three other AMPs showed no hemolytic activity under the conditions tested [Niu et al, 2008], suggesting that fusion to other peptides may provide a solution to the cytotoxicity issue. Further, the use of multiple types of AMPs may help reduce the chance of bacterial resistance because it increases the number of potential targets in the bacteria [Sørensen and Borregaard, 2005] and synergistic interactions make the individual peptides effective at lower concentrations [van der Linden et al, 2009]. Other strategies that should be considered depending on target organisms may include (1) fusion of SMAP-29 to a molecule (e.g., an antibody) that binds target bacteria to achieve targeted killing [Franzman et al, 2009], and (2) coupled use with a cell-penetrating peptide, such as Pep-1 and its derivatives [Morris et al, 2001;Zhu et al, 2006;Wagstaff and Jans, 2006], to facilitate killing intracellular bacteria.…”

Section: Use In Combinationmentioning

confidence: 99%

Cathelicidin peptide SMAP‐29: comprehensive review of its properties and potential as a novel class of antibiotics

Dawson

Liu

2009

Drug Development Research

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Sheep myeloid antimicrobial peptide of 29 amino acids (SMAP-29) is one of the most potent antimicrobial peptides known, with a broad spectrum of activity against bacteria, fungi, and viruses. It has also been shown to prevent infections in animals. SMAP-29 is an a-helical cathelicidin that acts rapidly to permeabilize membranes of susceptible organisms. However, it is also cytotoxic and hemolytic to mammalian cells. In this review, all published data on inhibition constants and hemolytic activities of SMAP-29 are brought together for the first time, including data for the peptide of 28 residues that lacks the C-terminal glycine and that also has the new C-terminal residue amidated. Both peptides have been called SMAP-29 in the literature. Antimicrobial activity of SMAP-29 variants (including ovispirins) against Grampositive bacteria is also comprehensively tabulated, and anomalies in the nomenclature of the ovispirins are highlighted. The secondary structure, mode of action, and structure-activity relationships of SMAP-29 are outlined, and the properties that indicate its therapeutic potential are identified; these are its broad-spectrum antimicrobial activity with high potency, rapid biocidal action, limited development of bacterial resistance, synthesis by recombinant technology, ability to bind lipopolysaccharide, and demonstrated protection against infection in animal models. The limitations of SMAP-29 are its high cytotoxicity and hemolytic activity, reduced activity under physiological conditions, and limited evidence for synergistic effects in combination with conventional antibiotics. Strategies with the potential to improve the selectivity toward pathogenic microorganisms over mammalian cells have been devised by the authors and are outlined. Drug Dev Res 70: 481-498, 2009.

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Synergistic effects of ovine-derived cathelicidins and other antimicrobials against Escherichia coli O157:H7 and Staphylococcus aureus 1056 MRSA

Cited by 25 publications

References 9 publications

Cathelicidins Inhibit Escherichia coli–Induced TLR2 and TLR4 Activation in a Viability-Dependent Manner

Cathelicidins Inhibit Escherichia coli–Induced TLR2 and TLR4 Activation in a Viability-Dependent Manner

Characterization of bioactive recombinant antimicrobial peptide parasin I fused with human lysozyme expressed in the yeast Pichia pastoris system

Cathelicidin peptide SMAP‐29: comprehensive review of its properties and potential as a novel class of antibiotics

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