Gut instinct: Salmonella bacteria's molecular tactics to cau...(Once the bacterium is taken up in the SC...),Health

As the Salmonella penetrates through the epithelial layer, it encounters a dense population of macrophages that normally act to engulf and digest pathogens and debris. Unlike other gut commensal microbesE. coli for exampleSalmonella is able to survive and replicate within SCV of these macrophages, which eventually transport it to organs including the liver and spleen. "The host cells isolate nutrients from bacteria," Shi explains. "They may deplete metal ions, nucleotides, and amino acids which are essential for bacterial life and growth. In this way, Salmonella are essentially starved to death."

But the Salmonella are prepared, and respond first by sensing the new conditions, then synthesizing proteins allowing them to acquire nutrients from this new environment while switching on genes girding the bacteria against destructive host peptides.

As Shi explains, a regulatory system allowing Salmonella to monitor and respond to rapidly changing conditions is made up of two proteins: PhoP and PhoQ. The PhoP/PhoQ regulators act as a master control, switching off invasion proteins when they are no longer required while switching on a new set of protein factors necessary for intracellular survival. In a domino effect, part of this transition activates magnesium transporters, which act to reestablish metal ion levels in the depleted conditions of the vacuole.

But now a problem arises. Salmonella must maintain proper Mg2+ concentration in their cytoplasm, though PhoP, once turned on, acts to continually increase these levels. The single master switch PhoP/PhoQ is not
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