New pneumococcal serotype 20C is a WciG O-acetyltransferase deficient variant of canonical serotype 20B

<i>Streptococcus pneumoniae</i> (pneumococcus) is a significant human pathogen known for producing a wide array of antigenically and structurally diverse capsule types, a fact that poses a serious challenge to the effectiveness of vaccines targeting pneumococcal capsule polysaccharide (PS). Herein, we provide a comprehensive analysis-genetic, antigenic, and biochemical of a newly identified capsule type, 20C, which differs from the canonical serotype 20B due to the inactivation of the capsule O-acetyltransferase gene, <i>wciG</i>. Our findings highlight how pneumococci can alter their capsule PS structure and immunological characteristics through minor genetic modifications. Since the appearance of new capsule types can directly affect pneumococcal conjugate vaccine (PCV) implementation, a deeper understanding of capsule PS at the genetic, immunological, and biochemical levels is critical for the development of future diagnostic tools and vaccines.