RNA chaperone activates Salmonella virulence program during infection.

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Organisms frequently possess proteins with overlapping functions, termed redundant proteins.
• In Salmonella Typhimurium, RNA chaperones CspC and CspE were initially considered to have redundant roles in virulence.
• Mutants lacking both CspC and CspE show reduced virulence, while single mutants exhibit wild-type virulence.

Purpose of the Study:

• To investigate the specific roles of CspC and CspE in Salmonella Typhimurium virulence.
• To elucidate the mechanism by which CspC influences virulence gene regulation.
• To determine the conditions under which CspC and CspE exhibit differential functions.

Main Methods:

• Construction and phenotypic analysis of Salmonella Typhimurium mutants lacking CspC, CspE, or both.
• Assessment of virulence gene activation, specifically the PhoP regulator, under varying pH conditions.
• In vitro analysis of CspC's effect on ugtL mRNA secondary structure and translation using purified components.

Main Results:

• CspC, but not CspE, is essential for activating the PhoP virulence regulator in Salmonella Typhimurium at mildly acidic pH, mimicking conditions inside host macrophages.
• This CspC-dependent activation is specific to mildly acidic environments; mutants lacking CspC behave normally under other PhoP-inducing conditions.
• CspC facilitates the translation of the virulence gene ugtL by resolving mRNA secondary structures that impede ribosome binding.

Conclusions:

• The apparent redundancy between CspC and CspE in Salmonella Typhimurium virulence is misleading; they possess distinct and critical functions.
• CspC plays a specific role in regulating virulence gene expression in response to the acidic environment encountered within host cells.
• This study highlights how seemingly interchangeable proteins can mediate crucial, condition-specific adaptations essential for bacterial survival and pathogenesis.