Isolation and molecular physiology of bacterial persisters Studies in Bacillus subtilis and Staphylococcus aureus

Persisters are phenotypic variation of microbial cells that are tolerant to harsh conditions such as antibiotic exposure and starvation. They have been confirmed as the major cause of recurrent and chronic infections, as well as one of the main contributors to the development of antibiotic resistance. Despite the severe impact of persisters and the value of knowing the mechanisms of their formation, this phenotype is still puzzling. Therefore, investigating the formation and characteristics of persisters is of great importance in persister prevention and elimination, holding considerable clinical relevance. In this project, we proposed an effective method to identify persisters from both treated Bacillus subtilis and Staphylococcus aureus cultures, which allows us to analyze isolated persisters at both single cell and population levels. Additionally, we described the molecular and physiological characteristics of persistent samples generated from different stress conditions, revealed both their similarities and distinctions. This investigation sheds light on the stress-specific nature of persisters, and the necessity of tailored treatment approaches to treat different persistent populations. Moreover, the potential application of antimicrobial peptides and synergistic antibiotic combinations in preventing persister formation and persister treatment has been tested, which provided valuable insights into persister eradication.