THERAPEUTIC POTENTIAL OF INHALED ALX-009 (OSCN-/ BLF) FOR THE TREATMENT OF ACHROMOBACTER SPP. INFECTIONS IN CYSTIC FIBROSIS.
C. Bechetoille*, Y. Sonmez*, L. Jubeau * and V. Juarez-Perez.
Recent epidemiologic studies in Europe and USA indicate that prevalence of Achromobacter spp. is increasing within the CF population. ALX-009 is a fixed combination of two endogenous compounds of the innate immune system, OSCN- and Lactoferrin (LF), both reduced in CF patients. OSCN- disturbs the bacterial machinery while LF either acts as iron chelator and/or by direct interaction with bacterial membranes. According to the current knowledge, particularly from data obtained with Burkholderia spp., the mode of action of ALX-009 may be described as follows:
• High concentration of OSCN- penetrates the cell and induces rapid bacterial killing by impairing the enzymes necessary to the respiratory pathways (Carlson et al. Infection and immunity. 1984, 44, 581). This effect last up to 6h,
• At lower concentrations, i.e. from 6-12h, OSCN- is still in contact with the surface of the bacterial wall and attacks the proteins involved in membrane transport
• In the meantime and up to 24h after addition of the compounds to the culture, bLF “relays” OSCN- hampering the regrowth of bacteria by direct contact with bacteria (Roseneau et al. Rom. J. Biochem. 2010. 47(2):203-209).
The combined effects of OSCN- /LF may offer an innovative multi-target strategy to fight resistant pathogens. Achromobacter spp. is a gram negative bacteria able to induce severe lung infections in these patients and for which therapeutic options are limited. In previous reports, Alaxia demonstrated the therapeutic potential of the drug ALX-009 on a large collection of Burkholderia spp. and other emergent bacteria in cystic fibrosis patients. The present study aims at evaluating the bactericidal capacity of ALX-009 against a large number of isolates of the multi-drug resistant bacteria Achromobacter spp.