Temporal transcriptomic changes during in vitro cultivation of the human tick-borne relapsing fever spirochete...

Clonal selection driven by antigenic variation enables immune evasion in Relapsing Fever Borrelia spirochetes, yet the mechanism and potential triggers for the rapid switch of the main serotype are not fully known. Tick-borne relapsing fever (TBRF) spirochetes of the genus Borrelia exhibit clonal selection by alternation in the expression of their variable major proteins (Vmp's) which drive antigenic variation followed by recurrent waves of bacteremia. In this study we analyzed exploratory transcriptomic variations during in-vitro growth of Borrelia persica in stable (37 °C) and stressed (39 °C) conditions. The observed vlp subfamily profiles of Borrelia persica showed decreasing alpha (p = 0.0014), gamma (p = 0.023), and delta (p = 0.002) transcript abundance and increasing beta (p = 0.003) transcript abundance over the sampled culture period. No significant changes were found in vlp expression when comparing between growth at 37 °C and 39 °C (vlp alpha, p = 0.923; vlp beta, p = 0.254; vlp gamma, p = 0.914; vlp delta, p = 0.645). Vlp expression changes were consistent in direction and repeatable across biological replicates. Among 80 examined stress-related genes, six were downregulated and one was upregulated at T1 relative to T0. The reciprocal pattern, where vlp alpha decreased sharply while vlp beta increased, provides an exploratory description of expression dynamics and a basis for future studies evaluating spontaneous clonal selection and antigenic diversity. The current study provides preliminary evidence for spontaneous antigenic variation and clonal selection in B. persica.