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Synergistic antibacterial and anti-inflammatory activity of temporin A and modified temporin B in vivo.

Capparelli R, Romanelli A, Iannaccone M, Nocerino N, Ripa R, Pensato S, Pedone C, Iannelli D - PLoS ONE (2009)

Bottom Line: Temporins are antimicrobial peptides secreted by the granular glands of the European red frog (Rana temporaria).Administration of 3.4 mg/Kg of temporin A (TA)+1.6 mg/Kg TB-YK, given to individual mice concurrently with a lethal dose of bacteria (gram positive or negative), rescued 100% of the animals.The model offers the possibility to test in a preclinical setting the true potential of TA and TB-YK in combination as antimicrobial and anti-inflammatory agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Soil, Plant, Environment and Animal Production Sciences, University of Naples Federico II, School of Biotechnological Sciences, Napoli, Italy. capparel@unina.it

ABSTRACT
Temporins are antimicrobial peptides secreted by the granular glands of the European red frog (Rana temporaria). They are 10-14 amino acid long polypeptides active prevalently against gram positive bacteria. This study shows that a synthetic temporin B analogue (TB-YK), acquires the capacity to act in synergism with temporin A and to exert antimicrobial and anti-inflammatory activity in vivo against gram positive and gram negative bacteria. Administration of 3.4 mg/Kg of temporin A (TA)+1.6 mg/Kg TB-YK, given to individual mice concurrently with a lethal dose of bacteria (gram positive or negative), rescued 100% of the animals. More importantly, the same doses of temporins, administered one week after experimental infection with a sub lethal dose of bacteria, sterilized 100% of the animals within 3-6 days. Also, it is described an animal model based on the use of sub lethal doses of bacteria, which closely mimics bacterial infection in humans. The model offers the possibility to test in a preclinical setting the true potential of TA and TB-YK in combination as antimicrobial and anti-inflammatory agents.

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Related in: MedlinePlus

Expression levels of cytokine genes in mice infected with S.enterica serovar Paratyphi B (105 CFU/mouse) and 6 days lose treated with temporins (35/75 pool).Each hystogram represents the mean value measured in 2 mice, each one tested in triplicate.
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pone-0007191-g009: Expression levels of cytokine genes in mice infected with S.enterica serovar Paratyphi B (105 CFU/mouse) and 6 days lose treated with temporins (35/75 pool).Each hystogram represents the mean value measured in 2 mice, each one tested in triplicate.

Mentions: Treated mice, compared to the untreated ones, showed lower levels of the pro-inflammatory cytokines TNF-α and INF-γ and higher levels of the anti-inflammatory cytokines IL-4 and IL-6, indicative of a more balanced Th1/Th2 response (Figure 8). To study the anti-inflammatory activity of temporins under conditions that more closely reproduce bacterial infection in humans, the experiment was repeated using a small initial inoculum of bacteria. Mice were infected with S. enterica serovar Typhimurium (105 CFU/mouse) and 6 days later treated with the 35/75 pool. The cytokine expression levels in the liver were monitored daily by RT-PCR. The experiment demonstrated that temporins bring the levels of the cytokines back to those of naïve mice within 5 days (Figure 9). The experiments on cytokines as described in this paragraph were repeated on mice infected with S. aureus and yielded very similar results.


Synergistic antibacterial and anti-inflammatory activity of temporin A and modified temporin B in vivo.

Capparelli R, Romanelli A, Iannaccone M, Nocerino N, Ripa R, Pensato S, Pedone C, Iannelli D - PLoS ONE (2009)

Expression levels of cytokine genes in mice infected with S.enterica serovar Paratyphi B (105 CFU/mouse) and 6 days lose treated with temporins (35/75 pool).Each hystogram represents the mean value measured in 2 mice, each one tested in triplicate.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747021&req=5

pone-0007191-g009: Expression levels of cytokine genes in mice infected with S.enterica serovar Paratyphi B (105 CFU/mouse) and 6 days lose treated with temporins (35/75 pool).Each hystogram represents the mean value measured in 2 mice, each one tested in triplicate.
Mentions: Treated mice, compared to the untreated ones, showed lower levels of the pro-inflammatory cytokines TNF-α and INF-γ and higher levels of the anti-inflammatory cytokines IL-4 and IL-6, indicative of a more balanced Th1/Th2 response (Figure 8). To study the anti-inflammatory activity of temporins under conditions that more closely reproduce bacterial infection in humans, the experiment was repeated using a small initial inoculum of bacteria. Mice were infected with S. enterica serovar Typhimurium (105 CFU/mouse) and 6 days later treated with the 35/75 pool. The cytokine expression levels in the liver were monitored daily by RT-PCR. The experiment demonstrated that temporins bring the levels of the cytokines back to those of naïve mice within 5 days (Figure 9). The experiments on cytokines as described in this paragraph were repeated on mice infected with S. aureus and yielded very similar results.

Bottom Line: Temporins are antimicrobial peptides secreted by the granular glands of the European red frog (Rana temporaria).Administration of 3.4 mg/Kg of temporin A (TA)+1.6 mg/Kg TB-YK, given to individual mice concurrently with a lethal dose of bacteria (gram positive or negative), rescued 100% of the animals.The model offers the possibility to test in a preclinical setting the true potential of TA and TB-YK in combination as antimicrobial and anti-inflammatory agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Soil, Plant, Environment and Animal Production Sciences, University of Naples Federico II, School of Biotechnological Sciences, Napoli, Italy. capparel@unina.it

ABSTRACT
Temporins are antimicrobial peptides secreted by the granular glands of the European red frog (Rana temporaria). They are 10-14 amino acid long polypeptides active prevalently against gram positive bacteria. This study shows that a synthetic temporin B analogue (TB-YK), acquires the capacity to act in synergism with temporin A and to exert antimicrobial and anti-inflammatory activity in vivo against gram positive and gram negative bacteria. Administration of 3.4 mg/Kg of temporin A (TA)+1.6 mg/Kg TB-YK, given to individual mice concurrently with a lethal dose of bacteria (gram positive or negative), rescued 100% of the animals. More importantly, the same doses of temporins, administered one week after experimental infection with a sub lethal dose of bacteria, sterilized 100% of the animals within 3-6 days. Also, it is described an animal model based on the use of sub lethal doses of bacteria, which closely mimics bacterial infection in humans. The model offers the possibility to test in a preclinical setting the true potential of TA and TB-YK in combination as antimicrobial and anti-inflammatory agents.

Show MeSH
Related in: MedlinePlus