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Vrla, G. D.

Publications and source records attributed to Vrla, G. D..

2 recordsLinked to original sources

C. elegans reads bacterial non-coding RNAs to learn pathogenic avoidance

C. elegans is exposed to many different bacteria in its environment, and must distinguish pathogenic from nutritious bacterial food sources. Here, we show that a single exposure to purified small RNAs isolated from pathogenic Pseudomonas aeruginosa (PA14) is sufficient to induce pathogen avoidance, both in the treated animals and in four subsequent generations of progeny. The RNA interference and piRNA pathways, the germline, and the ASI neuron are required for bacterial small RNA-induced avoidance behavior and transgenerational inheritance. A single non-coding RNA, P11, is both necessary and sufficient to convey learned avoidance of PA14, and its C. elegans target, maco-1, is required for avoidance. A natural microbiome Pseudomonas isolate, GRb0427, can induce avoidance via its small RNAs, and the wild C. elegans strain JU1580 responds similarly to bacterial sRNA. Our results suggest that this ncRNA-dependent mechanism evolved to survey the worms microbial environment, use this information to make appropriate behavioral decisions, and pass this information on to its progeny.

genetics

Surface association induces cytotoxic alkyl-quinolones in Pseudomonas aeruginosa

Surface attachment, an early step in the colonization of multiple host environments, activates the virulence of the human pathogen P. aeruginosa. However, the signaling pathways and downstream toxins specifically induced by surface association to stimulate P. aeruginosa virulence are not fully understood. Here, we demonstrate that alkyl-quinolone (AQ) secondary metabolites are rapidly induced upon surface association and represent a major class of surface-dependent cytotoxins. AQ cytotoxicity is direct and independent of other AQ functions like quorum sensing or PQS-specific activities like iron sequestration. Furthermore, the regulation of AQ production can explain the surface-dependent virulence regulation of the quorum sensing receptor, LasR, and the pilin-associated candidate mechanosensor, PilY1. PilY1 regulates surface-induced AQ production by repressing the AlgR-AlgZ two-component system. AQs also contribute to the known cytotoxicity of secreted outer membrane vesicles. These findings collectively explain previously mysterious aspects of virulence regulation and provide new avenues for the development of anti-infectives.

microbiology