Salmonellosis causes 3 million deaths per year and 1 billion people are affected worldwide. This disease is caused by Salmonella Enteritidis,and it is an important issue for the poultry and eggs industry. The problem increases with the bacterial resistance towards the allowed antibiotics. In Colombia, the government invests USD 1,3 billion per year to control salmonellosis and still it is not fully controlled. In this sense, bacteriophages are an alternative solution to control bacterial contamination and infections. This work presents the assessment of the evolutionary interaction of bacteriophage San23 with its host. San23 was chosen among 20 native phages, and the phage-host interaction was evaluated along 12 days. The model consisted of a microcosms set up with 107CFU/ml bacteria and 106PFU/ml phages in 6 ml of LB broth. After 48 hours,samples were taken, bacteria and phage were isolated,and 6ul of the lysate were transferred to new media; this was repeated until the 12th day. Once all the samples were collected,isolated bacteria from each time point were challenged against isolated phages from the previous,contemporary and posterior time point. Unexpectedly, the results showed more a mutational asymmetry dynamic instead of an antagonistic relationship. Then, we performed a genomic analysis of bacteria and phages obtained from the microcosms. Using Next-Generation sequencing, we sequenced the bacteria and phages genomes from the different time points. This information allowed us to detect the changes in the genomes, and identified the differences in proteins related to the bacterial resistance mechanisms. Among others,we found that a resistance mechanism probably used against San23 is a mutation at the receptor that binds the phage fibbers;based on this finding,we analysed the responses in the phage population genome. Taken together, these data provide a deep insight into the phage-host interaction and can serve as additional criteria to select phages for phage therapy.