Salmonella: Subverting Defences

Salmonella is known for causing bad cases of food-poisoning. Like all pathogens it has an arsenal of proteins and enzymes that help it wreak havoc on our bodies, but it’s greatest weapon of all is possibly ourselves…Intrigued? Read on.

Salmonella are peritrichous (that means they have whip-like flagella all over their surface) gram-negative rod shaped bacteria that are entero-invasive pathogens of humans. The Salmonella enterica strain S. typhimurium is the most common cause of salmonellosis which is seen as food poisoning with flu-like symptoms, vomiting and diarrhoea. As it is an easy and accessible gateway for pathogens to enter the human body, the gut is one of the most protected sites in the human body. The immune system has involved a great deal of defences in this area, including evolution of paneth cells that secrete antimicrobial peptides such as defensins, in combination with M cells and inter-epithelial dendritic cells for constant monitoring of the gut lumen via antigen sampling. A large amount of immune cells also exist in the basal lamina underneath the gastrointestinal epithelium. Neutrophils can also be rapidly recruited to sites of infection in the gut and can cross the epithelial barrier to gain access to the gut lumen.
Essentially, this is the Fort Knox of the human body.

So how does Salmonella get past all this?

Firstly, Salmonella enters the gastrointestinal tract with food and is protected from the stomach acid by the sheer bulk and matter of the food entering this system. Despite this, many Salmonella cells will die here due to the low pH of the stomach but enough will survive to reach the colon. The pathogen’s flagella is used to swim towards the intestinal epithelial cells here and other proteins mediate adherence to this surface. Once attached, a range of virulence factors ensure that the Salmonella penetrates through the M Cells and epithelial cells to invade the host tissues. At this stage of the infection symptoms can start to arise- the destruction of epithelial cells and the invasion of tissues means that vast quantities of fluid are lost as diarrhoea and the body sends ‘pain signals’ to the brain, resulting in the cramps of food poisoning.

At this stage, a healthy immune system has recognised that there is a threat via the recognition of Salmonella flagellar proteins and shed LPS. Among other responses, immune and epithelial cells secrete Interleukin-8 (IL-8), a compound that strongly attracts neutrophils to the site of infection. These cells are potent phagocytes of the immune system that can open up the epithelial barrier to reach the gut lumen, devouring and destroying any foreign object or pathogen in their path. Their recruitment to a site is a trademark of inflammation as this innate immune response is simply the recruitment of immune cells to a site of damage, infection or both. With these immune cells active, it should only be a matter of time now for the immune system to mop up the Salmonella infection ravaging your guts.

Oh, but Salmonella has different ideas. This sneaky pathogen has evolved to use our own immune responses and gut bacteria against us! Many pathogens have ‘learned’ to dampen down our natural inflammatory responses to extend their own survival, however it is thought that Salmonella has taken a different route altogether. It deliberately encourages the triggering of an inflammatory response (although it is dampened down to a degree, all good things in moderation) so that the epithelial barrier preventing Salmonella from disseminating throughout your body is disrupted by the neutrophil recruitment. The leaky tight junctions between the epithelial cells are now perfect opportunities for grabbing nutrients in the forms of fluid and ion secretion (i.e diarrhoea- Lovely) and for Salmonella to invade the gastrointestinal tissues with little effort.

Salmonella also utilises the commensal gut bacteria to its advantage. Normally our gut bacteria occupy most ‘living spaces’ in the gut so that pathogens find it difficult to get a foothold in. This natural microbiota produces toxic hydrogen sulphide (HS) gas as a by-product of fermenting carbohydrate sources in your gut (chicken meat is especially rich in sulphides) but this is quickly converted into the more harmless thiosulphate form (S2O32-) which normally passes through your guts like a warm, eggy breeze. But when the reactive oxygen species released by neutrophils in an attempt to kill the invading Salmonella contact this S2O32-, they instead react to form tetrasulphate (S4O62-). Salmonella has adapted to incorporate and utilise tetrasulphate in its respiratory chain, thus utilising our own gut bacteria against us. By using tetrasulphate, a compound that very few if any gastrointestinal bacteria can use, Salmonella has secured itself a plentiful resource in the gut lumen, one that allows it to outcompete and thrive in the gastrointestinal environment despite our protective flora’s best efforts.

Another way in which Salmonella has subverted our own defences is in sloughed off cells. When an epithelial cell is infected with any pathogen, the neighbouring cells will squeeze the infected cell out into the gut lumen to be passed out at the earliest opportunity. Sloughed off cells will naturally die, and sometimes break up while in the gut lumen. When this happens Salmonella can utilise the ethanolamine (2-amino-ethanol) that forms a large part of human cell membranes as a nutrient source, giving the pathogen another advantage over the residents in the gut lumen to thrive and grow to invasive levels. This combination of manipulating host inflammation and defences allows Salmonella to outcompete the natural gut flora to grow in the restricted environment of the gastrointestinal tract, but to also evade the immune system for that little bit longer.

So, is that it? Are we doomed? Has Salmonella got the upper hand once and for all? Not by a long shot. The human immune system is a determined thing, and most salmonella food poisoning while unpleasant is treatable by antibiotics at the moment. But, as I’ve mentioned in a previous post, the rise of antibiotic-resistant pathogens is accelerating and we better adapt to this harsh reality just as Salmonella has adapted to make the most out of its harsh environment.



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