Bringing Structure to Biology
The enemies of our enemies
The image in our calendar for October shows a virus which can kill a bacterium. A bacterium that is responsible a disease which affects over 15 million people each year. What can we learn from viruses that attack our own attackers?
More than a nasty cough
Nearly 59 000 people died of whooping cough in 2015, mainly in the developing world. Also known as Pertussis or the 100-day cough, it is caused by bacterium Bordetella pertussis and characteristic symptoms are fits of coughing, followed by a high-pitched ‘whoop’ sound as the sufferer breathes back in.
B. pertussis was first discovered in 1906, and vaccines became available for use in the 1940s. Though a number of antibiotics have been used more recently to treat the infection, these vaccines are still the primary method for prevention of the disease. In the 21st century, however, whooping cough has seen a resurgence in the Western world, most likely due to reductions in immunity levels combined with mutations helping the bacteria evade the immune response.
Attacking the bacterium
Over many years we have developed vaccines to resist attack by B. pertussis, but the bacterium already has its own attackers. Bordetella pertussis phage (BPP-1) is a virus that infects and kills B. pertussis. Like many viruses, BPP-1 has an icosahedral (football-shaped) head, called a capsid of about 670 Å in diameter which contains its genome. Electron microscopy studies of BPP-1 (PDB entry 3j4u) suggest that it is a hybrid virus. It has proteins in its capsid from two different lineages into which icosahedral viruses have been classified.
A 'Roll reversal'
The two proteins in the capsid are termed the major capsid protein (MCP) and the cement protein (CP). The BPP-1 capsid contains 420 copies of each one (Fig). The cement protein is so called as it stabilises and strengthens the capsid, which must withstand around 40 atmospheres of pressure (equivalent to about 400 metres below the sea) as the genome is forced inside. MCP has a shape called the jelly roll fold. This is found in other viruses, but in those the jelly roll is the major capsid protein not the cemener protein.
The BPP-1 capsid. CP is shown in blue and MCP in ivory
In BPP-1, the major capsid protein is also unusual as a viral protein. It has the same overall fold as other viral MCPs, for instance that from HK97 which attacks E. coli, but the parts of it occur in a different order giving the protein a new topology. One domain, termed the A domain has five beta strands arranged in a sheet, but how these are connected together has not been seen previously in any other virus.
The order of beta strand structural elements in the central portion of MCP. On the left, that from HK97 phage and on the right from BPP-1. The beta strands are shown as arrows coloured from blue to red in the order thay are connected. Loops between them are lines, black and dotted where they are the same between the 2 molecules, and solid colours where they differ.
A most unusual virus
These features of the capsid proteins aren’t the only unusual features of BPP-1. It’s capable of making large changes to its protein coding genes due to a so-called “diversity-generating retro-element (DGR)” which enables it to adapt rapidly to environmental change. This ability is exceedingly rare outside of eukaryotes and makes BPP-1 useful for biotechnology as a vector for a technique called phage-display, but also means it can keep a step ahead of any resistance mechanism that it’s host, B. pertussis might evolve. As antibiotic resistance becomes more and more of an issue, could viruses such as BPP-1, the enemies of our enemies, become really useful friends?
About the artwork
The image is an intaglio print by Yuen-Hang Li of Impington Village College. Three BPP-1 virus capsids are shown, depicted in blue. Striking colours have been chosen, with a bright blue virus on a fiery red and orange backdrop.