Lister Institute Fellow Serge Mostowy Publishes New Paper on Combating ‘Superbug’ Shigella

We are pleased to announce that Lister Institute Fellow Professor Serge Mostowy has recently published a significant new paper on the potential of septin proteins to combat ‘superbugs.’ In a major contribution to research on antimicrobial resistance, Professor Mostowy’s team have demonstrated that the proteins can act as ‘cellular police’ – identifying and trapping superbug cells, and eventually killing them.

The paper, entitled Septins Recognize and Entrap Dividing Bacterial Cells for Delivery to Lysosomes was published in the journal Cell Host & Microbe on the 12th of December 2018. It explains the actions of septins, a class of Guanosine-5′-triphosphate (GTP) binding proteins that are considered part of the cytoskeleton, when they come into the presence of the bacteria Shigella.

Shigella is one of the leading causes of diarrhoea around the world, and is classified as a top 12 pathogen posing a risk to human health by the World Health Organization (WHO). It is a very important infectious bacteria to study, both for its own sake and due to the implications that a better understanding of Shigella’s nature and responses might have for treating infectious diseases in general, particularly in terms of antibiotic resistance.

Professor Mostowy’s team are at the forefront of this field, and we have previously discussed his important work in this area. In this new paper Professor Mostowy has demonstrated that septins are able to affix to curved bacterial membranes through the presence of cardiolipin, a lipid found in the membrane of most bacteria and also forming part of the inner mitochondrial membrane.

The septins are ‘recruited’ to these sites of membrane curvature and, once in place, can assemble into cages surrounding growing bacterial cells. These cages inhibit the division of the bacterial cells, effectively slowing down or even stopping the growth and spread of the infection.

The cages carry out this process by recruiting autophagic and lysosomal machinery (naturally-occurring structures used in the normal disassembly, removal and recycling of non-functional cellular components) in order to kill bacterial cells. Cardiolipin has been found to enable and improve the identification of the invasive Shigella cells, kick-starting the process of septin cage entrapment.

It was also found that bacterial mutants that lack cardiolipin are less likely to be trapped in septin cages, adding further weight to the conclusion that its presence assists with fighting infection in this manner. Professor Mostowy said:

“The rise of ‘superbugs’ is one of the greatest global health challenges we face. New drugs to tackle antimicrobial resistance are crucial but they are costly and all likely to be met with resistance. We must therefore also look at other, novel ways to control bacterial infection.”

“By applying cutting edge microscopy techniques, only available in the last few years, to study the cellular immune response to Shigella, we now have clear evidence that septins can be a new ‘natural’ weapon in the fight against AMR. Remarkably, these proteins act as host cell ‘sensors’ to recognise actively dividing bacteria, the exact bacterial population that causes disease, for entrapment. In addition to Shigella, this may also apply to a wide variety of invasive bacterial pathogens such as Pseudomonas and Staphylococcus.”

The potential implications of this research are very exciting, as Professor Mostowy explains;

“We are actively working to engineer this discovery for human health application. If we can use drugs to boost septin caging, we have a new way to stop infection.”

Professor Mostowy is a professor at The London School of Hygiene & Tropical Medicine, a globally-renowned research and education institution with a substantial track record in public health. You can find out more about Professor Mostowy’s work on his laboratory’s website at Mostowy Lab.

We are pleased to have played a role in supporting Professor Mostowy through a Lister Institute Research Prize and are looking forward to hearing more about his team’s important progress in the vitally important field of bacterial infection research.