How a rare chemical crosslink gives spirochaete bacteria their remarkable ability to burrow through tissues
Imagine a motor so efficient it can propel a cell through gel-like substances, a motor so rugged it lasts a lifetime, and so tiny that thousands could fit on the tip of a human hair.
This isn't science fiction; it's the bacterial flagellum, the outboard motor of the microbial world. But for spirochaetes—the corkscrew-shaped bacteria that cause diseases like Lyme disease and syphilis—this motor has a unique and powerful secret. Unlike most bacteria, whose flagella spin outside the cell, spirochaetes have their flagella tucked inside their outer sheath, like the engine of a submarine.
To withstand the immense internal forces of this unique "internal" rotation, a critical component, the hook, is fortified with a rare and incredibly strong chemical latch: lysinoalanine.
To understand the magic of lysinoalanine, we must first understand the flagellum's structure. Think of it as an engine with three main parts:
Embedded in the cell wall, this is the power source. It uses a flow of charged particles (protons) to rotate, much like an electric motor.
The long, whip-like propeller that extends outwards (or, in spirochaetes, is contained internally) and pushes the bacterium along.
The critical connecting piece between the motor and the filament. It acts as a universal joint, flexing and bending to transmit the motor's rotation into useful propulsion.
In most bacteria, the hook is a flexible coupling. But in spirochaetes, it needs to be much more. It must act as a rigid driveshaft to transmit torque from the internal motor, forcing the entire cell body to rotate and corkscrew through its environment. This is where lysinoalanine comes in.
Lysinoalanine (LAL) is not a standard amino acid you find in a protein recipe. It's a crosslink—a covalent bond formed between two amino acids that are part of the protein chain, stitching different parts of the molecule together.
This crosslink dramatically increases the hook's mechanical strength and rigidity, allowing it to function as a robust driveshaft without snapping under the constant, high-torque rotation.
How did scientists prove that lysinoalanine was the key to the spirochaete hook's strength? A landmark study on the hook protein (FlgE) of Treponema pallidum, the bacterium that causes syphilis, provided the definitive evidence.
Researchers first grew the bacteria and used detergents and biochemical techniques to gently isolate the intact flagellar hooks, separating them from the rest of the cell.
They then used specific enzymes, like a molecular scissor, to chop the large hook protein into smaller, manageable peptides.
The complex mixture of peptides was fed into a mass spectrometer. This instrument acts as a molecular scale, measuring the precise mass of each fragment.
The scientists scanned the mass data, looking for a peptide with a specific "mass fingerprint" that would only exist if a lysine and a cysteine had fused to form a lysinoalanine crosslink.
The mass spectrometer data revealed exactly what they were looking for: peptides with masses corresponding to fragments containing the lysinoalanine crosslink. This was the first direct chemical evidence that the spirochaete hook is fortified with this unique staple.
| Peptide Sequence Region | Measured Mass (Da) | Crosslink Type |
|---|---|---|
| A...K-LAL-C...B | 1456.72 | Lysinoalanine (LAL) |
| X...K-LAL-Y...Z | 1898.91 | Lysinoalanine (LAL) |
| Control (No enzyme) | N/A | N/A |
| Bacterium | Hook Protein | Key Structural Feature | Relative Flexibility | Proposed Function |
|---|---|---|---|---|
| Treponema pallidum (Spirochaete) | FlgE | Multiple LAL crosslinks | Rigid / Low Flex | Driveshaft for corkscrew motility |
| Escherichia coli (Standard) | FlgE | No LAL crosslinks | Highly Flexible | Universal joint for external flagella |
The discovery of lysinoalanine in the spirochaete flagellar hook is more than just a fascinating piece of basic science. It solves a long-standing mechanical puzzle: how a biological structure can be both incredibly strong and assembled inside a living cell. This "molecular staple" is a masterpiece of evolutionary engineering.
Understanding this unique chemistry opens new doors. Could we design drugs that specifically prevent the formation of lysinoalanine, effectively "unstitching" the hook and crippling the bacterium's ability to move and cause disease?
For pathogens like Treponema pallidum and Borrelia burgdorferi (Lyme disease), which are notoriously difficult to treat, this hook protein presents a promising and unique target for a new generation of antibiotics.
The secret latch of the bacterial motor may one day be the key that locks it down for good.