Protection by peptide HH2 against an invasive <i>Staphylococcus aureus</i> infection in mice, compared to a negative control peptide HH17.

<p>Mice were pretreated with saline (control) or 4 mg/kg peptide (IP) in saline, and infected 4 hours later with approximately 1.0×10⁹ CFU of <i>S. aureus</i>. Twenty-four hours post infection, mice were euthanized and the peritoneal lavage taken, and plated on Mueller Hinton agar. The graph is representative data from a series of 2 independent experiments. *represents p<0.05.</p

Effect of IDR peptides on the growth of <i>M. tuberculosis</i> and cytotoxicity in monocytic cells.

<p>(A) <i>Mycobacterium tuberculosis</i> strain H37Rv was incubated with increasing concentrations of the indicated peptides in doubling dilutions ranging from 128 to 8 µg/mL to determine the minimal inhibitory concentration (MIC). (B) The effect on monocyte viability was assessed by incubating increasing concentrations of these peptides with cells and assessing the integrity of the cytoplasmic membrane. The data is expressed as means ± standard deviation of 6 independent experiments with each one performed in duplicate.</p

Effect of antimicrobial peptide treatment on pulmonary bacilli burdens and tissue damage (pneumonia) during experimental tuberculosis kinetic.

<p>(A) Mice were infected with the drug-sensitive H37Rv Mtb strain, and after 60 days were treated, three times per week, with ∼1 mg/kg of the indicated peptide in 100 mL of saline solution. HH2 and 1018 decreased the lung bacillary loads in comparison with untreated mice, whereas 1002 showed no significant changes. (B) Percentage of the lung surface affected by pneumonia as determined by automated morphometry. Results are expressed as means ± standard deviations, P<0.05 * or P<0.01** were considered statistically significant. Both 1018 and HH2 peptides significantly decreased the pneumonic area when compared with the control group. The graph is representative data from a series of 3 independent experiments.</p

Direct antimicrobial activity of the IDR peptides vs. Gram negative pathogen <i>Pseudomonas aeruginosa</i> and Gram positive pathogen.

<p><i>Staphylococcus aureus</i> - Mean of three independent experiment.</p>1<p>Taken from Wieczorek et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059119#pone.0059119-Wieczorek1" target="_blank">[19]</a>.</p

Immunomodulatory activities of peptides IDR-HH2, IDR-1002 and IDR 1018 in human peripheral blood mononuclear cells (PBMC).

<p>Cells were stimulated with 20 µg/ml of peptide.</p>1<p>Experiments were performed 2–4 times and means are presented. All values for peptide treated cells represent significant induction relative to the untreated control (p<0.05) for the two chemokines MCP-1 and Gro-α, and significant reduction in LPS stimulated TNF-α relative to the LPS-treated but peptide-untreated control. There was no significant induction of TNF-α by the peptides themselves. The data for IDR-1018 are consistent with those presented in Wieczorek et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059119#pone.0059119-Wieczorek1" target="_blank">[19]</a>.</p

Effect of antimicrobial peptides on the treatment of mice infected with a drug-resistant strain.

<p>(A) Animals were infected with the MDR strain and after 60 days treated three times per week with 32 µg in 100 µL of saline solution of the indicated peptide. Compared to the control untreated animals, IDR peptides HH2 and 1018 induced a significant decrease in lung bacillary loads. (B) Measurement of the area of consolidation of pneumonia showed that only HH2 and 1018 significantly reduced the pneumonic areas when compared with control mice. The data is expressed as means ± standard deviation of 3 independent experiments; p<0.01 indicated with a bar and **over the two bars was considered statistically significant.</p

Representative electron microscopy micrographs of <i>Mycobacterium tuberculosis</i> strain H37Rv treated with high concentrations of IDR peptides.

<p>(A) Control bacteria show thick homogeneous electron lucent cell wall (asterisk) and cytoplasm with some electron dense granules (63,000x); (B) Incubation with peptide 1002 induces abnormalities in the cell wall, such as thinning, budding and partial dissolution (arrows) (100,000x). (C) Peptide HH2 induces complete disappearance of the cell wall with electron lucent cytoplasm (asterisks) or homogenous cell wall thinning and condensation (arrows) with slight electron lucent change of the cytoplasm (80,000x). (D) Incubation with peptide 1018 produced a peripheral electron dense rim with areas of rupture and dissolution (arrows) in the cell wall, which also have irregular electron dense condensations (asterisk) and an electron lucent halo around the cytoplasm (100,000x). All bars in the figures represent 5 µm. The micrographs are representative of 2 independent experiments.</p