Salmonella biofilms program innate immunity for persistence in Caenorhabditis elegans

Abstract

Significance Salmonella resides as an intracellular pathogen in eukaryotic hosts and causes diarrhea or typhoid fever. In a small but alarming proportion of infected humans, Salmonella exists asymptomatically as biofilms, a basis for long-term disease transmission. Although Salmonella biofilms have been observed in chronically infected mice, mechanisms underlying why and how such multicellular aggregates are formed in vivo remain poorly understood. We exposed optically transparent Caenorhabditis elegans to Salmonella and observed the progression of infection in intestines from free-living cells to static aggregates. We discovered that a secreted toxin is down-regulated when Salmonella forms biofilms, leading to an adaptive advantage in chronic infections. Hence, Salmonella biofilms enable dormancy to prolong in vivo existence. The adaptive in vivo mechanisms underlying the switch in Salmonella enterica lifestyles from the infectious form to a dormant form remain unknown. We employed Caenorhabditis elegans as a heterologous host to understand the temporal dynamics of Salmonella pathogenesis and to identify its lifestyle form in vivo. We discovered that Salmonella exists as sessile aggregates, or in vivo biofilms, in the persistently infected C. elegans gut. In the absence of in vivo biofilms, Salmonella killed the host more rapidly by actively inhibiting innate immune pathways. Regulatory cross-talk between two major Salmonella pathogenicity islands, SPI-1 and SPI-2, was responsible for biofilm-induced changes in host physiology during persistent infection. Thus, biofilm formation is a survival strategy in long-term infections, as prolonging host survival is beneficial for the parasitic lifestyle.