Some infectious bacteria like NTHI, which is responsible for conjunctivitis or “pink eye”, middle ear infections and sinusitis, defend themselves from immune attack by appropriating the very molecules sent to destroy them. Researchers describe how they discovered the mechanisms that enable this in NTHI (short for Nontypeable Haemophilus influenzae) in an article published this month in the journal PLoS Pathogens.

It seems that barely a month goes by without a new account of how a strain of bacteria or some other pathogen has developed a new trick to get around our immune defences. The temptation to view this as “cleverness” on their part is strong, and we forget that because of their huge numbers and short lifecycle they have the chance to spawn multitudes of new mutations, from which only a handful needs to emerge with a survival advantage.

What is particularly interesting about this latest rather “elegant” example, described by lead study author Dr Kevin M. Mason, principal investigator in the Center for Microbial Pathogenesis at The Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, in the USA, and colleagues, is that this is the first to show bacteria using a cell transporter system to secure their survival.

Our immune systems are constantly vigilant against pathogens like bacteria that scavange for any opportunity to invade and use our resources for their own ends: this is the nature of infection. As a first line of defence against such invasions, the immune system despatches a group of molecules called host-derived antimicrobial peptides or AMPs which seek out and destroy the undesirables. AMPs’ secret weapon is their ability to push through the outer skin of bacteria cells because it is quite permeable.

But, in response to this, bacteria like NTHI have evolved a series of countermeasures. They have remodelled their outer membrane so it is less permeable.

Most of the time NTHI just sits harmlessly in the upper respiratory tract, but now and again it transforms into a more harmful form, which then leads to infections like conjunctivitis, sinusitis, acute “otitis media” (middle ear infection), and complications of cystic fibrosis.

Mason told the press that when NTHI transforms to the more pathogenic version, it appears to use what are called Sap proteins to arm itself against attack by AMPs (Sap stands for “sensitivity to antimicrobial peptides”). We already knew this, he said, but what remained unclear, was just how the Sap transporter complex protects against AMPs.

To look into this further, Mason and colleagues carried out a series of tests on laboratory animals with middle ear infections similar to those that happen in humans.

They had already discovered previously that NTHI bacteria lacking the protein SapA were more vulnerable to attack from AMPs.

In the new study, they examine more closely how the bacterial cell’s Sap transporter system recognizes and ushers the host AMPs into itself. It appears without this system, the bacteria cannot survive in the host, as Mason explained:

“It seems that NTHI senses the presence of these immune molecules, steals them from the host and arms itself to protect against future attacks.”

The bacteria cells suck in the AMPs and once inside, set about degrading them. Then, by reconstructing their membranes, they look like they have already been attacked, which protects them from being further assailed by more AMPs.

“Basically, transporting AMPs acts as a counter strategy to evade innate immune defense and ultimately benefits the bacterium nutritionally,” said Mason.

He and his colleagues suggest the Sap transporter system could be a new target for drugs that use AMP derivatives as alternatives to antibiotics as a way to treat infections caused by NTHI.

He said they want eventually to be able to block this “uptake system” and thereby starve the bacteria of their essential nutrients:

“If we could develop a small molecule inhibitor that could block binding and transport, we could render NTHI susceptible to immune attack, while preserving the body’s normal bacteria that are often disrupted by conventional antibiotic use,” explained Mason.

Written by Catharine Paddock PhD