Indiana University-Purdue University Indianapolis (IUPUI) / The patients with Cystic fibrosis (CF), an inherent genetic disorder, suffer from chronic
bacterial infection in the lung. In CF, modification of epithelial cells leads to alteration of
the lung environment, such as inhibition of ciliary bacterial clearance and accumulation
of thickened mucus in the airways. Exploiting these conditions, opportunistic pathogens
like Pseudomonas aeruginosa cause lifelong persistent infection in the CF lung by
forming into antibiotic-resistant aggregated communities called biofilms. Airway
infections as well as inflammation are the two major presentations of CF lung disease. P.
aeruginosa strains isolated from CF lungs often contain mutations in the mucA gene, and
this mutation results in higher level expression of bacterial polysaccharides and toxic
lipoproteins. In a previous work, we have found a putative lipoprotein gene (PA4326)
which is overexpressed in antibiotic-induced biofilm formed on cultured CF-derived
airway cells. In the current work, we speculated that this particular putative lipoprotein
affects cellular cytotoxicity and immune-stimulation in the epithelial cells. We found that
mutation of this gene (ΔPA4326) results in reduced airway cell killing without affecting
other common virulence factors.Moreover, we observed that this gene was able to stimulate secretion of the proinflammatory
cytokine IL-8 from host cells. Interestingly, we also found that ΔPA4326
mutant strains produced less pyocyanin exotoxin compared to the wild type. Furthermore,
our results suggest that PA4326 regulates expression of the pyocyanin biosynthesis gene
phzM, leading to the reduced pyocyanin phenotype. Overall, these findings implicate
PA4326 as a virulence factor in Pseudomonas aeruginosa. In the future, understating the
molecular interplay between the epithelial cells and putative lipoproteins like PA4326
may lead to development of novel anti-inflammatory therapies that would lessen the
suffering of CF patients.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/5629 |
| Date | January 2014 |
| Creators | Akhand, Saeed Salehin |
| Contributors | Anderson, Gregory G., Chang, Hua-Chen, Nelson, David, Atkinson, Simon |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Rights | Attribution-NonCommercial-NoDerivs 3.0 United States, http://creativecommons.org/licenses/by-nc-nd/3.0/us/ |
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