Role of Neisseria meningitidis luxS in cell-to-cell signaling and bacteremic infection

Abstract

Numerous pathogenic bacteria contain luxS, which is required for autoinducer-2 production. Here, we demonstrate that Neisseria meningitidis contains a functional copy of luxS that is necessary for full meningococcal virulence; strains with a luxS deletion are defective for bacteremia, a prerequisite of meningococcal pathogenesis.

FIG. 1.

(A) Complementation of E. coli DH5α with luxS_Nm. The growth profiles and extracellular AI-2 activity of E. coli DH5α carrying either pGEM T-Easy or the same vector containing luxS_Nm in the forward or reverse orientation were measured. Growth profiles: empty vector, closed squares; luxS_Nm in forward orientation, closed circles; luxS_Nm in reverse orientation, open circles. AI-2 activity: V. harveyi BB120 (wild type, after 24 h), black bar; luxS_Nm in forward orientation, grey bars; luxS_Nm in reverse orientation, white bars. Activities are presented as the fold increase of bioluminescence in relation to E. coli DH5α carrying an empty vector at the respective time point. (B) Growth profiles and AI-2 activity of N. meningitidis. N. meningitidis strains MC58 (closed circles) and MC58ΔluxS (open circles) were grown, and the optical densities at 600 nm of cultures were measured. Culture supernatants of MC58 (grey bars), MC58ΔluxS (white bars), and V. harveyi BB120 (black bar) were assayed for AI-2 activity. Activities are presented as the fold increase of bioluminescence in relation to the control (sterile medium) at the respective time points. The results for MC58ΔluxS^Ect were identical to those for the wild type and are not shown. For panels A and B, single representative experiments are shown, although similar results were obtained on three occasions for both assays.

FIG. 2.

MC58ΔluxS is defective for bacteremic infection compared with the parental strain, MC58. This defect is restored by supplying a single, intact copy of luxS in trans to MC58ΔluxS (MC58ΔluxS^Ect); the difference in the virulences of MC58ΔluxS and MC58ΔluxS^Ect is highly significant (P < 0.001). The CI is the proportion of the strains in the bloodstream 21 to 24 h following infection with a 1:1 ratio of the strains.