Salmonella typhi uses CFTR to enter intestinal epithelial cells

Area of Science:

• Microbiology
• Genetics
• Immunology

Background:

• Cystic fibrosis transmembrane conductance regulator (CFTR) mutations cause cystic fibrosis (CF).
• Heterozygous carriers of CFTR mutations may exhibit enhanced resistance to certain infectious diseases, potentially explaining the high prevalence of mutant alleles in specific populations.
• Typhoid fever, caused by Salmonella typhi, is a significant global health concern.

Purpose of the Study:

• To investigate the role of CFTR in Salmonella typhi entry into host cells.
• To determine if CFTR genotype influences susceptibility to typhoid fever.
• To explore the potential mechanism of CFTR-mediated Salmonella typhi translocation.

Main Methods:

• In vitro studies using epithelial cells expressing wild-type or mutant CFTR to assess Salmonella typhi uptake.
• In vivo studies using Cftr-genotyped mice to evaluate Salmonella typhi translocation.
• Use of monoclonal antibodies and synthetic peptides targeting CFTR to block bacterial entry.
• Immunoelectron microscopy to visualize CFTR-Salmonella typhi interactions.

Main Results:

• Salmonella typhi, but not Salmonella typhimurium, utilizes wild-type CFTR for entry into epithelial cells.
• Cells expressing wild-type CFTR showed higher Salmonella typhi internalization compared to cells with the common deltaF508 CFTR mutation.
• Heterozygous deltaF508 Cftr mice exhibited significantly reduced Salmonella typhi translocation compared to wild-type mice.
• CFTR genotype did not affect Salmonella typhimurium translocation.
• Reduced CFTR expression in heterozygotes correlated with decreased Salmonella typhi binding in the submucosa.

Conclusions:

• CFTR plays a crucial role in the entry of Salmonella typhi into host cells.
• Diminished CFTR levels in individuals heterozygous for CFTR mutations may confer resistance to typhoid fever.
• Targeting CFTR could be a potential strategy for developing novel approaches to combat typhoid fever.