Chitosan-Aspirin Combination Inhibits Quorum-Sensing Synthases (lasI and rhlI) in Pseudomonas aeruginosa.

BACKGROUND: Quorum sensing (QS) controls the virulence of P. aeruginosa. This study aims to determine the anti-QS activity of aspirin alone and in combination with chitosan to reach maximum inhibition. We tested ten virulent Pseudomonas aeruginosa (P. aeruginosa) isolates and screened for N-acyl homoserine lactone (AHL) production using Agrobacterium tumefaciens as a biosensor. P. aeruginosa isolates were treated with sub-minimum inhibitory concentrations (MICs) of aspirin and chitosan-aspirin. We used broth microdilution and checkerboard titration methods to determine the MICs and the synergistic effect of these two compounds, respectively. Real-time polymerase chain reaction (PCR) was used to estimate the anti-QS activity of the aspirin-chitosan combination on the expression of lasI and rhlI genes. RESULTS: Aspirin decreased the motility and production of AHLs, pyocyanin, and biofilm. Chitosan potentiated the inhibitory effect of aspirin. The chitosan-aspirin combination inhibited lasI and rhlI gene expression in PAO1 (ATCC 15692) by 7.12- and 0.92-fold, respectively. In clinical isolates, the expression of lasI and rhlI was decreased by 1.76 × 102- and 1.63 × 104-fold, respectively. Molecular docking analysis revealed that aspirin could fit into the active sites of the QS synthases lasI and rhlI with a high binding affinity, causing conformational changes that resulted in their inhibition. CONCLUSIONS: The chitosan-aspirin combination provides new insights into treating virulent and resistant P. aeruginosa.

Chitosan and chitosan-zinc oxide nanocomposite inhibit expression of LasI and RhlI genes and quorum sensing dependent virulence factors of Pseudomonas aeruginosa.

The great ability of Pseudomonas aeruginosa to cause chronic infection is attributed to several virulence factors, biofilm formation, intrinsic and acquired resistance to many antibiotics. Anti-quorum sensing (QS) and anti-virulence therapy are promising alternatives to the existing antibiotic therapy. In this study, the effect of chitosan and the prepared chitosan-zinc oxide (CH/ZnO) nanocomposite on QS-dependent virulence factors and acyl homoserine lactone "AHL" production was studied. The chemical structure of the prepared CH/ZnO nanocomposite was characterized by FT-IR spectrum and XRD. The thermal stability and particle size were determined. Chitosan causes a significant decrease in AHL, biofilm, pyocyanin production and motility of P. aeruginosa. CH/ZnO nanocomposite augments the inhibitory activity of chitosan in both phenotypic and genotypic levels. Both chitosan and CH/ZnO nanocomposite downregulate the expression of LasI and RhlI genes using quantitative real-time PCR. The expression of RhlI gene in PAO1 is reduced by 1240 folds after treatment with CH/ZnO nanocomposite. The expression of LasI and RhlI genes in clinical isolates is reduced by 1778.07 and 627.29 folds upon treatment with CH/ZnO. These promising results may find a rescue in the battle of fighting P. aeruginosa by repressing its QS-dependent virulence factors.

Importance of serum IL-18 and RANTES as markers for breast carcinoma progression.

BACKGROUND: Interleukin-18 (IL-18), a cytokine that plays an important role in the T-cell-helper response, acts as an angiogenic factor and a tumor suppressor. RANTES (regulated upon activation normal T-cells expressed and secreted) is a member of the C-C chemokine family with chemoattractant activity for a variety of cell types. High incidence and intensity of RANTES were noted in advanced breast carcinoma. AIM OF THE STUDY: To correlate the levels of RANTES and IL-18 in serum of breast cancer patients with bone or other organ metastasis compared to breast cancer patients without metastasis and healthy controls and to estimate the role of each of them as a prognostic marker for the progression of the disease. PATIENTS AND METHODS: The study was conducted on 60 breast cancer patients (25 cases with no metastasis and 35 cases with metastasis) who were admitted to the outpatient clinic of the NCI, Cairo University during the period from March 2004 to September 2004 and 30 apparently healthy controls who were volunteers at the blood bank of the NCI, Cairo University. RESULTS: Showed that there was a statistically significant difference between the level of IL-18 in breast cancer patients without metastasis and the control group (p<0.05) while there was a highly significant difference between the metastatic group and the control group (p<0.001). There was a significant increase in IL-18 levels between metastatic and non-metastatic cases (p<0.01). RANTES showed a significant increase in breast cancer cases with no metastasis and the control group (p<0.05) and it showed a highly significant increase in metastatic patients compared to controls (p<0.001). There was no significant increase in the level of RANTES in metastatic compared to non-metastatic patients (p>0.05). CONCLUSIONS: IL-18 is an important non invasive marker suspecting metastasis. Even though RANTES levels were higher in cancer patients compared to controls, its role in staging of breast cancer was not clear in this study.