N-acetyl-glucosamine primes Pseudomonas aeruginosa for virulence through a type IV pili/cAMP-mediated morphology transition.

A microbe is pathogenic when it manages to survive in its host and, often, is able to proliferate. Thus, virulence entails coping with host defenses in parallel to dissemination and/or attack of the host. How the pathogen endures the attack by effectors of the immune response remains insufficiently understood. Here, we report that planktonic Pseudomonas aeruginosa is not immediately virulent in a Drosophila model of acute infection. Bacteria undergo a maturation step called priming, which is required for transition to virulence. Primed bacteria switch to a bacillus shape, only in vivo, proliferate and resist the action of a specific combination of antimicrobial peptides. This priming mechanism requires an interplay between two major effectors of the type IV pili (T4P), FimV and Vfr, which enhance lateral cell wall peptidoglycan synthesis. Interestingly, N-acetyl-muramic acid (NAM) abolishes the virulence of the injected bacteria, which become round, and prevents the localization of the T4P hub protein FimV at bacterial poles, and cAMP signaling. In contrast, N-acetyl glucosamine (NAG) counteracts the action of NAM by promoting FimV polar placement. In fact, NAG alone accelerates the speed of P. aeruginosa priming in a PilJ-dependent manner. This suggests that the NAG sensed by microorganisms is a common signal that promotes virulence through a morphological switch, both in bacteria and pathogenic dimorphic yeasts.