PHENICS

Streptococcus pneumoniae (or pneumococcus) is a major human pathogen and the leading cause of lower respiratory tract infections. While genetically acquired resistance allows bacteria to grow in the presence of antibiotics, phenotypic tolerance enables survival during treatment, with cells resuming growth once the antibiotic is no longer present. Certain subpopulations, such as persisters and VBNC (Viable But Not Culturable) cells, are particularly tolerant to multiple antibiotics and associated with the recalcitrance of chronic infections, highlighting how heterogeneity can shape different phenotypic outcomes across the bacterial population. Persisters have been reported in bacteria, but despite the presence of chronic pneumococcal infections, specific molecular determinants have not been yet identified for pneumococcal persister formation. Moreover, although over 100 bacterial species can enter the VBNC state, there have been no investigations into pneumococcal VBNCs, revealing a critical gap in our understanding of this pathogen's biology. The aim of PHENICS is to explore how phenotypic heterogeneity drives cell survival in S. pneumoniae, with a focus on characterizing its persister and VBNC states. The molecular mechanisms driving the formation of these states, as well as the transition from one to another, will be studied using both untargeted and targeted approaches, with particular attention paid to the role of protein phosphorylation.