Extracellular Pneumococcal Serine Proteases Affect Nasopharyngeal Colonization

Area of Science:

• Microbiology
• Infectious Diseases
• Bacterial Pathogenesis

Background:

• *Streptococcus pneumoniae* (pneumococcus) utilizes host factors, including serine proteases like plasmin(ogen), for colonization.
• Pneumococci express multiple serine proteases (HtrA, PrtA, SFP, CbpG) with strain-dependent variations.
• The role of these proteases in pneumococcal colonization and disease remains incompletely understood.

Purpose of the Study:

• To investigate the contribution of pneumococcal serine proteases to bacterial adherence and colonization.
• To evaluate the role of these proteases in a mouse model of acute lung infection.
• To assess the potential of pneumococcal serine proteases as antimicrobial targets.

Main Methods:

• Generation of serine protease deletion mutants (double and triple) in *S. pneumoniae* serotypes 19F and 4.
• Adherence assays using Detroit-562 epithelial cells.
• Mouse intranasal colonization model (CD-1 mice) monitored for 14 days.
• Acute pneumonia model in mice using bioluminescent strains for real-time imaging and survival analysis.

Main Results:

• Mutants lacking serine proteases or expressing only a single protease exhibited reduced adherence to epithelial cells.
• Serine protease-deficient mutants showed significantly abrogated nasopharyngeal colonization in mice.
• A specific mutant (TIGR4 *lux* expressing only PrtA) displayed reduced virulence in an acute pneumonia model.

Conclusions:

• Pneumococcal serine proteases are essential for efficient colonization of the nasopharynx.
• These enzymes play a limited role in the pathogenesis of acute pneumonia and invasive disease.
• Serine proteases represent potential targets for novel antimicrobials aimed at reducing pneumococcal transmission.