Salmonella’s adaptability comes with evolutionary trade-offs
A recent "Nature Communications" paper by the Hardt (IMB) and Vorholt groups reveals how Salmonella's glpT gene acts as a double-edged sword: boosting replication in macrophages but hindering growth in the gut lumen during infection in mice.
Salmonella enterica, a common cause of foodborne illnesses, owes much of its high prevalence to its adaptability. A recent study showcased the limits of its metabolic adaptation by demonstrating how the glpT gene has a context-dependent fitness effect depending on Salmonella’s location during infection.
In the initial stages of infection, within the gut lumen, glpT-deficient mutants exhibited a growth advantage. This advantage is attributed to the high phosphate concentrations in the gut, where the absence of GlpT prevents excessive phosphate import, thereby benefiting the bacteria. However, this benefit is transient. As the infection progresses and Salmonella encounters macrophages—immune cells responsible for engulfing pathogens—the lack of GlpT becomes detrimental. Inside these cells, GlpT plays a crucial role for bacterial survival and replication. Thus, glpT-deficient mutants are less fit within macrophages.
This study underscores the concept of antagonistic pleiotropy, where a single gene can have opposing effects on an organism's fitness depending on the context. For Salmonella, the expression of glpT is a trade-off: disadvantageous in the nutrient-rich environment of the gut lumen but advantageous within the hostile confines of macrophages. Exploiting such trade-offs could open avenues for targeted therapeutic interventions.
Link to the paper in external page "Nature Communications".