Disease relevance of lasA

• Revised nucleotide sequence of the lasA gene from Pseudomonas aeruginosa PAO1 [1].
• These results indicate that insertional inactivation of lasA renders P. aeruginosa avirulent in a murine model of keratitis and that neither LasR nor elastase production is required for the establishment and maintenance of corneal infection [2].
• Positive correlation of algD transcription to lasB and lasA transcription by populations of Pseudomonas aeruginosa in the lungs of patients with cystic fibrosis [3].
• This lasA protein produced in E. coli activated the extracellular elastase produced by the P. aeruginosa mutant, PAO-E64 [4].

High impact information on lasA

• This residual activity was abolished by inactivation of lasB in PAO-E64, a lasA-deficient mutant, demonstrating that it was due to the lasA gene product [5].
• Northern analysis demonstrated that, like lasB, lasA is transcriptionally controlled by the lasR gene product [5].
• When transcriptional fusion plasmids were used to quantify the expression of the lasB and lasA genes in P. aeruginosa PAO1-I and PAO-R1, the lasB::lacZ fusion in PAO-R1 showed only 3.5% as much activity as it did in PAO1-I, while the activity of the lasA::lacZ fusion in PAO-R1 was 27.8% of that in PAO1-I [2].
• In scarified corneas, P. aeruginosa PAO-A1 (LasA negative) or PAO-B1A1 (LasB and LasA negative) at a dose of 10(8) CFU per eye caused very mild or no disease following infection; however, the defect in PAO-A1 could not be complemented by supplying a functional copy of lasA either on a plasmid or inserted into the chromosome [2].
• We also observed that PAO-A1 was closer to the parental phenotype, with respect to elastolytic and proteolytic activities, than the previously characterized, chemically induced lasA mutant PAO-E64 [6].

Biological context of lasA

• Complementation with lasA did not restore virulence in either model of infection [7].
• The full elastolytic phenotype of Pseudomonas aeruginosa requires lasB, the structural gene for elastase, its transcriptional activator lasR, and lasA [5].
• Thus the lasA gene product has a direct effect on broadening the substrate specificity of secreted proelastase, as well as a second role (direct or indirect) in the secretion of elastase [8].
• Pseudomonas aeruginosa lasA gene: determination of the transcription start point and analysis of the promoter/regulatory region [9].
• The lasA gene was physically mapped on plasmid pELA1 by deletion analysis and transposon mutagenesis [10].

Anatomical context of lasA

• Mutation of lasA and lasB reduces Pseudomonas aeruginosa invasion of epithelial cells [11].

Associations of lasA with chemical compounds

• Mutation of lasA and/or lasB reduced P. aeruginosa invasion, which was not fully restored by extracellularly added LasB, P. aeruginosa conditioned medium containing LasA and LasB, or EGTA pretreatment of cells [11].

Other interactions of lasA

• Known QS-regulated extracellular proteins, including elastase (lasB), LasA protease (lasA) and alkaline metalloproteinase (aprA) were also detected [12].
• This correlation may not indicate a direct association between algD and either lasA or lasB [3].
• These RNAs were blotted and hybridized with probes to P. aeruginosa lasA, lasB, and toxA [13].
• The direction of transcription of lasA was determined with a promoterless chloramphenicol acetyltransferase cartridge [10].

Analytical, diagnostic and therapeutic context of lasA

• Large aggregates were isolated from porcine bronchoalveolar lavage fluid and incubated with supernatants from P. aeruginosa cultures (PAO1, parent strain; PAO1-A1, lasA-negative mutant; PAO1-B1, elastase-negative mutant) or purified elastase [14].
• N-terminal sequence analysis identified the protein as a fragment of the lasA gene product (P.A. Schad and B.H. Iglewski, J. Bacteriol. 170:2784-2789, 1988) [15].

References