To harm or not to harm? On the evolution and expression of virulence in group A streptococci

• Streptococcus pyogenes causes asymptomatic, superficial symptomatic, and invasive infections.
• The two noninvasive types of infection maximize fitness in different conditions.
• Virulence factors are adaptations for superficial symptomatic infection.
• Invasive infection is a non-adaptive side effect of the virulence factors.

Group A streptococci (GAS) cause three different types of infection (sensu lato) with distinct levels of virulence: asymptomatic colonization, superficial symptomatic infection, and invasive infection. To address why this pattern with several infection types has evolved, we combine mechanistic understanding from infection medicine with recent theory from evolutionary ecology. We propose that asymptomatic colonization and superficial symptomatic infection exploit different states of the host epithelium to maximize transmission between hosts in different epidemiological conditions, whereas the ability of the bacteria to cause invasive infection is a non-adaptive side effect of traits required for superficial symptomatic infection.