The regulation of the curli adhesin requires much more than the CsgD regulator in Salmonella enterica serovar Typhi

Authors : Camille Ou, Charles M. Dozois, France Daigle

Read the original article published on September 9, 2023 in Scientific Reports : https://www.nature.com/articles/s41598-023-42027-y

The Salmonella bacterium produces filamentous structures called curli. These structures enable it to adhere to various surfaces and form bacterial films (biofilms), providing protection against the immune system and antibiotics. There are several serovars of Salmonella with different characteristics. For instance, the Salmonella enterica serovar Typhi (S. Typhi) bacterium is responsible for typhoid fever, a potentially deadly disease affecting 11 to 21 million people annually. S. Typhi has the unique ability to form biofilms in the gallbladder of infected individuals. On the other hand, its cousin, the Salmonella enterica serovar Typhimurium (S. Typhimurium) bacterium, causes gastrointestinal problems and foodborne illnesses. Unlike S. Typhi, it can infect various animals in addition to humans. Despite their differences, these two bacteria share a significant portion of their DNA, making it relevant to compare them to better understand their functioning.

The exact functioning of curli in S. Typhi remains a mystery.  Some indicators, such as the presence of antibodies in individuals who have had typhoid fever, suggest a potential production of curli during infection. However, experiments have shown that S. Typhi does not produce curli under conditions favorable for S. Typhimurium. This suggests that S. Typhi follows its own rules regarding the formation of bacterial biofilms. Trials in culture media mimicking infection conditions have revealed that curli are particularly active in an environment with low salt and nutrients. The influence of temperature and oxygen on curli genes has also been studied, showing notable differences between S. Typhi and S. Typhimurium.

In S. Typhimurium, a key regulator named CsgD orchestrates the production of curli. However, in S. Typhi, it has been observed that the equivalent of S. Typhi's CsgD has a reduced ability to bind to the DNA of curli genes compared to that of S. Typhimurium. Furthermore, even by replacing S. Typhi's CsgD with that of S. Typhimurium, the characteristics associated with curli production are still not recovered in S. Typhi. This suggests a distinct regulation of curli in S. Typhi. Alterations are found in other genes of the curli system in S. Typhi. Genetic substitution experiments of the entire curli system with that of S. Typhimurium have confirmed that these alterations do not contribute to the difference in curli expression in S. Typhi.

In conclusion, the regulation of curli genes in S. Typhi differs from that in S. Typhimurium, involving genetic alterations, notably in the CsgD gene. Understanding the regulatory mechanisms is crucial as curli influence how the bacterium produces biofilms and interacts with the immune system and intestinal cells. This opens avenues for developing new strategies to better control infections caused by S. Typhi, as well as other Salmonella found in poultry and pig farming.