Opposing selective forces for expression of the gonococcal lactoferrin receptor

Area of Science:

• Microbiology
• Infectious Diseases
• Bacterial Pathogenesis

Background:

• Neisseria gonorrhoeae utilizes human transferrin (Tf) receptors for infection.
• Many isolates lack lactoferrin (Lf) receptors, despite Lf's abundance in mucosal environments.
• Tf receptor deficiency renders gonococci unable to infect male volunteers.

Purpose of the Study:

• To investigate the role of Lf and Tf receptors in Neisseria gonorrhoeae infection.
• To determine if Lf receptor expression is sufficient for infection and confers a competitive advantage.
• To characterize the prevalence and genetic basis of Lf receptor expression in clinical isolates.

Main Methods:

• Experimental infections in male volunteers using isogenic gonococcal mutants.
• Mixed infection models to assess competitive advantages.
• Analysis of clinical isolates for Lf receptor expression and genetic deletions (lbpB-lbpA).

Main Results:

• Lf receptor expression alone was sufficient for infection in the absence of Tf receptors.
• Co-expression of Lf and Tf receptors provided a competitive advantage over Tf receptor-only strains.
• Nearly 50% of clinical isolates lacked Lf receptors, often due to an identical lbpB-lbpA deletion.
• Among Lf+ strains, 70% expressed LbpA but not LbpB.

Conclusions:

• Selective pressures favor Lf receptor expression in the male urethra.
• Conversely, other niches may exert pressure against Lf receptor expression.
• The Lf receptor plays a significant role in gonococcal pathogenesis and adaptation.