Science1 publisher2 min readPublished
Chlamydia packs its infectious DNA with sphingolipids taken from the host cell
University of Würzburg researchers report that Chlamydia fills about 90 percent of its infectious-form DNA package with host sphingolipids. Disrupting that lipid-DNA bridge could block infection at its start, they say, though the binding site is not yet resolved.
The Scientist · Science desk
What happened
- Combining expansion microscopy with cryo-electron tomography, the team found stacks of membrane forming a structural bridge between the bacterium's inner envelope and its DNA core.
- The pathogen alternates between infectious elementary bodies that survive outside cells and reticular bodies that replicate once inside a host.
- An elementary body measures just 200 to 300 nanometers, below the resolution of an ordinary light microscope.
- Because they could not be resolved optically, chlamydiae were mistaken for viruses until the 1960s.
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Why it matters
- capability Chlamydia cannot reproduce outside a host and takes its sphingolipids from human metabolism, so a drug that broke the lipid-DNA bridge would hit a step the bacterium cannot supply for itself.
- constraint No such drug can be designed from this work yet: the contact between lipid and DNA sits below the study's roughly 30-nanometer resolution, so the atomic binding site is undefined.
- precedent Whether the same packaging appears in other specialized bacteria is untested; if it does, a single mechanism could become a target across several pathogens.
The surprising part is the timing: the sphingolipid moves in and out of the DNA package as the bacterium develops. [11] "To our surprise, in our experiments we observed the highly dynamic incorporation and removal of a sphingomyelin derivative in bacterial nucleoids during the developmental cycle," said Thomas Rudel. [11] In the group's reading, lipid metabolism is not just a supply line for the cell envelope. It regulates when the genome becomes readable, and the release of the DNA from its lipid wrapping is the moment infection begins. [14]
The genome is otherwise held very tightly. During the infectious phase, when the bacterium lives as an elementary body outside any cell, its DNA is compressed into a dense nucleoid that shields the genetic material. [5] It builds this inside a compartment carved out of the host, an inclusion whose colonies often grow larger than the host cell's own nucleus. [3]
Seeing inside a structure that small took a workaround. Expansion microscopy enlarges the specimen instead of the image. The sample is set in a water-swellable hydrogel that grows to as much as eight times its original size, pulling labeled molecules far enough apart that an ordinary light microscope can resolve them. [12]
The study was published in Nature Communications by a team at the University of Würzburg led by Rudel, head of the Chair of Microbiology there, with Marcel Rühling and Fabienne Wagner as co-first authors. [8] Chlamydia trachomatis is one of the most common causes of sexually transmitted infection worldwide. [1]
What to watch
- A follow-up that resolves the lipid-DNA contact below 30 nanometers to define an actual binding site.
- Tests of whether other obligate intracellular bacteria pack their DNA with host lipids the same way.
- The first compound shown to disrupt the lipid-DNA bridge in an infection model.