Corneal Infections in Mice with Toxin A and Elastase Mutants of Pseudomonas aeruginosa

Abstract

The data presented indicate that in experimental infections of the mouse cornea, toxin A of Pseudomonas aeruginosa contributes to the organism's pathogenicity, whereas active elastase may not be required. After traumatization, corneas were infected with wild-type parental toxin A-producing strains, two toxin A-deficient mutants (Tox-), or an elastase mutant. The infections produced by both Tox- mutants were less severe than infections produced by their parental strains. Furthermore, the Tox- mutants were not able to persist in the eyes as long as their parental strains. Addition of subdamaging doses of exogenous toxin A to eyes infected with the Tox- mutant PA103-29 significantly increased is virulence. The course of infection and the resulting corneal damage produced by the elastase mutant were indistinguishable from those of its parental strain.

Protease IV, a Unique Extracellular Protease and Virulence Factor from Pseudomonas aeruginosa

“…b One unit of protease IV activity was defined as ⌬A/min ϫ total assay volume/sample volume ϫ E@410 nm ϫ light path (cm) where the extinction coefficient (E) of the product (paranitroanilide) at 410 nm was 9.75 and the light path was 0.53 cm (21 proteases associated with virulence (17)(18)(19)(20)(21)(22)(23)28). Research is currently in progress to determine the therapeutic value of protease inhibitors that are reactive with protease IV in reducing tissue damage that occurs during Pseudomonas infections.…”

“…PA103-29, like its parent (PA103), is deficient in elastase and alkaline protease, but unlike PA103, is also deficient in exotoxin A (19,27,28).…”

“…P. aeruginosa secretes alkaline protease and two elastases (A and B) that have been characterized as exoenzymes and virulence factors (17)(18)(19)(20)(21)(22)(23). Invasiveness of P. aeruginosa in burn patients correlates with elastase production (22).…”

Pseudomonas aeruginosa mediated apoptosis requires the ADP-ribosylating activity of ExoS

“…To successfully colonize and maintain an infectious cycle the organism carefully orchestrates production of a suite of virulence determinants including pili (Hahn, 1997 ;Wall & Kaiser, 1999) and non-pilus adhesins (Simpson et al, 1995), extracellular enzymes (Ohman et al, 1980 ;Salyers & Whitt, 1994), and exotoxins (Iglewski & Kabat, 1975). Some virulence factors are produced and secreted directly into the host cell using the cell-contact-mediated type III secretion machinery.…”

Management of bacterial keratitis: beyond exorcism towards consideration of organism and host factors

“…51,52 Intrastromal injection of purified elastase alone also results in severe corneal damage. Inhibition of elastase activity with 2-mercaptoacetyl-L-phenylalanine-L-leucine 53 prevents keratolysis.…”