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New study sheds light on how Salmonella spreads in the body

last modified May 27, 2016 12:23 PM
Research could have major implications for improving treatment and vaccination.

Findings of Cambridge scientists, published today in the journal PLoS Pathogens, show a new mechanism used by bacteria to spread in the body with the potential to identify targets to prevent the dissemination of the infection process.

Salmonella enterica is a major threat to public health, causing systemic diseases (typhoid and paratyphoid fever), gastroenteritis and non-typhoidal septicaemia (NTS) in humans and in many animal species worldwide. In the natural infection, salmonellae are typically acquired from the environment by oral ingestion of contaminated water or food or by contact with a carrier.  Current vaccines and treatments for S. enterica infections are not sufficiently effective, and there is a need to develop new therapeutic strategies.

Dr Andrew Grant, lead author of the study from the University of Cambridge, said: “A key unanswered question in infectious diseases is how pathogens such as Salmonella grow at the single-cell level and spread in the body.  This gap in our knowledge is hampering our ability to target therapy and vaccines with accuracy.”

During infection, salmonellae are found mainly within cells of the immune system where they are thought to grow and persist.  To do so the bacteria adapt to their surrounding environment and resist the antimicrobial activity of the cell.  Research from the Cambridge group has shown that the situation is more complex in that the bacteria must also escape from infected cells to spread to distant sites in the body, avoiding the local escalation of the immune response and thus playing a ‘catch me if you can’ game with the host immune system.

A body of knowledge has been built using in vitro (test tube) cell culture experiments that indicates that replication of Salmonella enterica within host cells in vitro is somewhat dependent on the bacteria making a syringe-like structure, called a Type 3 Secretory System (T3SS). This then injects bacterial proteins into the host cell, which in turn enhance bacterial replication inside that cell.  This T3SS is encoded by genes in a region of the bacterial chromosome called Salmonella Pathogenicity Island 2 (or SPI-2). Translating this cell culture work into whole animals, it has become accepted dogma that the SPI-2 T3SS is also required for bacterial intracellular replication in cells inside the body.

However, using fluorescence and confocal microscopy (which are imaging techniques), the Cambridge team has dispelled this dogma concerning the requirement for the SPI-2 T3SS for intracellular replication in the body. The researchers have shown that mutants lacking SPI-2 can reach high numbers within individual host cells, a situation that does not happen in in vitro cell culture.

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