# Lipid scavenging by the Lyme disease spirochete Borrelia burgdorferi

## TL;DR

This study reveals how the Lyme disease bacterium Borrelia burgdorferi scavenges lipids from its host to build its cell membrane, which could lead to new diagnostic tests or vaccines.

## Contribution

The paper provides the first comprehensive lipidomic analysis of B. burgdorferi and links lipid scavenging to gene expression and virulence.

## Key findings

- B. burgdorferi scavenges lipids from its environment to form its cell membrane.
- Lipid availability in the medium affects the expression of virulence-related genes like ospA and ospC.
- Scavenged lipids may serve as antigenic targets for immune responses and vaccine development.

## Abstract

Lyme disease is caused by the host-adapted spirochete Borrelia burgdorferi. With a genome of only 1.5 mbp, B. burgdorferi is dependent on metabolites scavenged from their vertebrate and invertebrate hosts for growth. These scavenged nutrients include several lipid precursors: the spirochete is auxotrophic for fatty acids and cholesterol, and also accumulates environmental phospholipids. Comprehensive lipidomic analysis of B. burgdorferi by LC MS/MS was used to identify previously undescribed membrane components. These include some likely scavenged from the culture medium and some which may be synthesized de novo via unknown pathways. Changes in fatty acid composition as cells enter stationary phase suggest that scavenging of environmental lipids is preferential to de novo synthesis, while transcriptomics suggests that this may be due to the energetic cost of synthesizing glycerol phosphate precursors. In media supplemented with excess phospholipids, scavenged lipids can be found at high concentrations in cells, suggesting that the membranes of infecting bacteria are likely to be partly shaped by the host environment. Transcriptomic analysis also show a link between environmental lipids and the expression of virulence-associated surface lipoproteins including reciprocal regulation of ospA and ospC. Given that borrelial membrane lipids are known to be antigenic during infection, these findings identify potential new targets for the development of diagnostic tests or vaccines.

Lyme disease is caused by a bacterium, Borrelia burgdorferi, which has an unusually small genome; it scavenges most of the nutrients it needs to survive from its hosts. This scavenging is critical to bacterial survival during the infectious cycle and to colonization of humans. The components of the bacterial cell membrane, which is the interface between the bacteria and its hosts, are largely stolen from the host environment. Some membrane lipids are the targets of antibodies produced during Lyme disease, and therefore these lipids could be the targets of new diagnostic tests or vaccines. However, the chemical composition of the B. burgdorferi cell membranes has not been fully described. We use mass spectrometry to completely characterize the lipid content of the bacteria, revealing the spectrum of membrane components that may be presented to the immune system during infection. We also find that the presence of lipids in the growth medium alters the expression of infection-associated bacterial genes, suggesting a link between the maintenance of the bacterial membrane and the ability to persist in humans to cause disease.