# Dissection of amino acid acquisition pathways demonstrates that amino acid starvation of Borrelia burgdorferi results in a (p)ppGpp-independent maladaptive response

## TL;DR

This study shows that Borrelia burgdorferi, the Lyme disease bacterium, cannot adapt to amino acid starvation using a common bacterial stress response mechanism.

## Contribution

The paper reveals that B. burgdorferi lacks a (p)ppGpp-dependent response to amino acid starvation, leading to maladaptive outcomes.

## Key findings

- Peptide transport and the BB0401 transporter are essential for B. burgdorferi viability during infection.
- Amino acid starvation does not trigger the canonical stringent response in B. burgdorferi.
- The bacterium shows maladaptive phenotypes under severe amino acid stress.

## Abstract

Borrelia burgdorferi, the causative agent of Lyme disease, is well known for its unique physiology and enzootic cycle. Building on previous work showing peptide transport is essential for viability, we endeavored to clearly define the impact of peptide starvation on the spirochete and directly compare peptide starvation to targeted free amino acid starvation. Herein, we confirm the ability of a putative glutamate transporter, BB0401, to transport glutamate and aspartate as well as demonstrate its requirement for viability. Using conditional mutants for both peptide transport and BB0401, we characterize these systems throughout the enzootic cycle, confirming their essential role during murine infection and revealing that they are dispensable during prolonged colonization of the tick midgut. We broadly define the metabolic perturbations resulting from these starvation models and show, even under the most severe amino acid stress, B. burgdorferi is unable to modulate its physiological response via the canonical (p)ppGpp-driven stringent response.

Amino acid starvation of Borrelia burgdorferi does not induce a physiological response via the canonical (p)ppGpp-driven stringent response and results in severe maladaptive phenotypes.