The increasing impact of phloem-restricted bacteria on economically important crops has led to renewed interest in understanding the pathogenesis at the genomic and histological levels of these diseases. The genus Candidatus Liberibacter is associated with economically devastating diseases, highlighting Candidatus Liberibacter asiaticus (CLas) and Candidatus Liberibacter solanaceraum (CLso) in citrus and vegetables. Plant-pathogen interaction studies are limited due to the non-culturable nature of the pathogenic species of the genus Ca. Liberibacter, as well as the lack of experimental models. The objective of this work was to implement a model for the study of bacteria of the genus Candidatus Liberibacter, using tomato-CLso as an experimental model. Through a time course analysis of the tomato-CLso infective process, it was determined that there is a direct correlation between the bacterial load and symptom development, differentiated into early, intermediate and late stages. Additionally, a comparative transcriptional analysis of antibacterial defense marker genes (PR-P1, miR160, and miR393) determined that the response of these genes in the tomato-CLso and lime-CLas pathosystems are equivalent. Our results demonstrate that the tomato-CLso system represents an important model for the study of the interaction between plants and non-cultivable phloem restricted bacteria.