Genome-Wide Evaluation of the Interplay between Caenorhabditis elegans and Yersinia pseudotuberculosis duringIn VivoBiofilm Formation

Abstract

The formation of an incapacitating biofilm onCaenorhabditis elegansbyYersinia pseudotuberculosisrepresents a tractable model for investigating the genetic basis for host-pathogen interplay during the biofilm-mediated infection of a living surface. Previously we established a role for quorum sensing (QS) and the master motility regulator, FlhDC, in biofilm formation byY. pseudotuberculosisonC. elegans. To obtain further genome-wide insights, we used transcriptomic analysis to obtain comparative information onC. elegansin the presence and absence of biofilm and on wild-typeY. pseudotuberculosisandY. pseudotuberculosisQS mutants. Infection ofC. eleganswith the wild-typeY. pseudotuberculosisresulted in the differential regulation of numerous genes, including a distinct subset of nematode C-lectin (clec) and fatty acid desaturase (fat) genes. Evaluation of the correspondingC. elegansclec-49andfat-3deletion mutants showed delayed biofilm formation and abolished biofilm formation, respectively. Transcriptomic analysis ofY. pseudotuberculosisrevealed that genes located in both of the histidine utilization (hut) operons were upregulated in both QS andflhDCmutants. In addition, mutation of the regulatory genehutCresulted in the loss of biofilm, increased expression offlhDC, and enhanced swimming motility. These data are consistent with the existence of a regulatory cascade in which the Hut pathway links QS andflhDC. This work also indicates that biofilm formation byY. pseudotuberculosisonC. elegansis an interactive process during which the initial attachment/recognition ofYersiniato/byC. elegansis followed by bacterial growth and biofilm formation.