Salmonella enterica serovar Typhi is a human-restricted pathogen and the primary etiologic agent of typhoid fever with an incidence of 21 million cases each year, resulting in 200,000 deaths annually. About 3–5% of the individuals with an acute clinical or subclinical infection ultimately develop a chronic asymptomatic carrier state. These new chronic carriers are being added to the existing pool every year. This chronic carriage state not only serves as a reservoir for further spread of the disease via bacterial shedding in feces but is also being reported to be associated with malignant transformations in the biliary system. The acute and chronic carrier states are also becoming challenging to resolve with antibiotics due to the emergence of multiple drug-resistant strains. Moreover, biofilm formation is another hindrance in eliminating the infection. It is crucial to understand the development of each of these states to design and test targeted approaches to resolve the more recalcitrant chronic carriage. Bacteriophage therapy is emerging as one of the potential alternatives to deal with acute and chronic infection associated with biofilm formation. In this review, we have discussed the natural process of biofilm formation along with the intelligent role of bacteriophages to resolve such complicated infections, particularly in relation to typhoid.
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