Phase variation in pneumococcal populations during carriage in the human nasopharynx

Area of Science:

• Microbiology
• Genetics
• Mathematical Biology

Background:

• Streptococcus pneumoniae causes pneumonia, septicaemia, and meningitis.
• Asymptomatic nasopharyngeal colonization precedes invasive disease, but the transition mechanism is unclear.
• A phase-variable Type I restriction-modification system (SpnIII) affects capsule expression and colonization.

Purpose of the Study:

• To investigate the role of SpnIII phase variation in Streptococcus pneumoniae colonization.
• To develop a mathematical model predicting SpnIII phase variation dynamics.
• To analyze SpnIII allele patterns in human nasopharyngeal samples.

Main Methods:

• Development of a Markov chain model for phase variation prediction.
• Analysis of Streptococcus pneumoniae samples from the Experimental Human Pneumococcal Carriage (EHPC) project.
• Mathematical modeling to compare observed allele patterns with stochastic predictions.

Main Results:

• The SpnIII restriction-modification system influences Streptococcus pneumoniae colonization.
• Observed SpnIII allele expression patterns in human nasopharyngeal carriage deviate significantly from random stochastic switching.
• Mathematical modeling highlights non-random dynamics in SpnIII allele frequencies.

Conclusions:

• Phase variation of the SpnIII system is a key factor in pneumococcal colonization dynamics.
• Non-stochastic mechanisms likely regulate SpnIII allele expression during human carriage.
• Alternative methylation patterns are crucial for understanding pneumococcal colonization and pathogenesis.