Pathoadaptation of the passerine-associated Salmonella enterica serovar Typhimurium lineage to the avian host

Author summary During Salmonella enterica evolution, many different ecological niches have been effectively occupied by this highly diverse bacterial pathogen. While many S. enterica serovars successfully maintained their ability to infect and colonize in a wide-array of host species, a few biotypes have evolved to colonize and cause a disease in only one or a small group of hosts. The evolutionary dynamic and the mechanisms shaping the host-specificity of Salmonella adapted strains are important to better understand Salmonella pathogenicity and its ecology, but still not fully understood. Here, we report genetic and phenotypic characterization of a S. Typhimurium strain that was isolated from several wild sparrows in Israel. This strain presented unique phenotypic profile that included impaired biofilm formation, high sensitivity to oxidative stress and reduced intracellular replication in non-phagocytic cells. In addition, while this strain was able to cause high inflammatory disease in an avian host, it was highly attenuated in the mouse model. Genome analysis identified that specific genetic signatures found in the sparrow strain are more frequently associated with poultry isolates than clinical isolates of S. Typhimurium. These genetic features are expected to accumulatively contribute toward the adaptation of this strain to birds. Salmonella enterica is a diverse bacterial pathogen and a primary cause of human and animal infections. While many S. enterica serovars present a broad host-specificity, several specialized pathotypes have been adapted to colonize and cause disease in one or limited numbers of host species. The underlying mechanisms defining Salmonella host-specificity are far from understood. Here, we present genetic analysis, phenotypic characterization and virulence profiling of a monophasic S. enterica serovar Typhimurium strain that was isolated from several wild sparrows in Israel. Whole genome sequencing and complete assembly of its genome demonstrate a unique genetic signature that includes the integration of the BTP1 prophage, loss of the virulence plasmid, pSLT and pseudogene accumulation in multiple T3SS-2 effectors (sseJ, steC, gogB, sseK2, and sseK3), catalase (katE), tetrathionate respiration (ttrB) and several adhesion/ colonization factors (lpfD, fimH, bigA, ratB, siiC and siiE) encoded genes. Correspondingly, this strain demonstrates impaired biofilm formation, intolerance to oxidative stress and compromised intracellular replication within non-phagocytic host cells. Moreover, while this strain showed attenuated pathogenicity in the mouse, it was highly virulent and caused an inflammatory disease in an avian host. Overall, our findings demonstrate a unique phenotypic profile and genetic makeup of an overlooked S. Typhimurium sparrow-associated lineage and present distinct genetic signatures that are likely to contribute to its pathoadaptation to passerine birds.

Automated summary

Salmonella enterica is a highly diverse bacterial pathogen that infects humans and animals. While many serovars of S. enterica have a broad host specificity, some pathotypes have evolved to cause disease in limited host species. The mechanisms underlying the host specificity of Salmonella are not fully understood. This study provides genetic analysis, phenotypic characterization, and virulence profiling of a monophasic S. enterica serovar Typhimurium strain isolated from wild sparrows in Israel, revealing unique genetic features and phenotypic profiles that contribute to its adaptation to birds.