Structure, Function, and Regulation of LytA: The N-Acetylmuramoyl-L-alanine Amidase Driving the ‘Suicidal Tendencies’ of Streptococcus pneumoniae— A Review

Streptococcus pneumoniae (pneumococcus) is a significant human pathogen responsible for a range of diseases from mild infections to invasive pneumococcal disease, particularly affecting children, the elderly, and immunocompromised individuals. Despite pneumococcal conjugate vaccines reducing the incidence of pneumococcal diseases, challenges persist due to serotype diversity, vaccine coverage gaps, and antibiotic resistance. The LytA autolysin, an N-acetylmuramoyl-L-alanine amidase, is a key enzyme in pneumococcal biology, regulating autolysis and contributing to virulence by facilitating bacterial clearance, inflammation, and biofilm dynamics. LytA also plays an important role in pneumococcal immune evasion by modulating complement activation. Its activity is influenced by environmental factors, genetic regulation, and spatial control and is linked to competence for genetic transformation. Beyond its biological role, LytA is a potential therapeutic target, with studies exploring its application in bacteriolytic treatments, vaccine development, and synergistic antibiotic strategies. Various compounds, including synthetic peptides, plant extracts, and small molecules, have been investigated for their ability to induce LytA-mediated bacterial lysis. Future research aims to develop novel anti-pneumococcal strategies leveraging LytA’s properties, while also addressing limitations in vaccine efficacy and emerging antibiotic resistance. Human challenge models and animal studies continue to refine our understanding of pneumococcal pathogenesis and treatment.