Featured Research

from universities, journals, and other organizations

New study sheds light on how Salmonella spreads in the body

Date:
December 6, 2012
Source:
University of Cambridge
Summary:
Scientists have discovered a new mechanism used by bacteria to spread in the body. The mechanism offers the potential to identify targets to prevent the dissemination of the infection process.

Findings of Cambridge scientists, published December 6 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.

Related Articles


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.

The researchers, from the Mastroeni and Maskell laboratories at the University of Cambridge's Department of Veterinary Medicine, investigated this phenomenon further and made the surprising discovery that salmonellae lacking the SPI-2 T3SS remain trapped inside cells and cannot spread in the body. One idea is that this will in turn lead to the arrest of bacterial division as a consequence of spatial or nutritional constraints. Despite growing to high numbers per cell, these mutants are much less able to grow overall in the body because far fewer cells become infected due to the greatly reduced ability of the bacteria to escape from the original infected cells.

These findings call into question the usefulness of some in vitro experimental systems that, when used in isolation, do not usefully represent the very complex structure of mammalian organisms.

The team also presented a new role for the NADPH phagocyte oxidase (Phox) (a host mechanism which generates reactive oxygen species which can inhibit the growth and/or kill the bacteria) in the control of Salmonella infection. They observed that this system inhibits bacterial escape from host cells, and that normally the SPI-2-encoded T3SS counters this system to facilitate bacterial exit from infected cells. This highlights a previously unknown interplay between SPI-2 T3SS and innate immunity in the dynamics of within-host bacterial growth and spread. The research shows that in the absence of an active Phox, SPI-2 T3SS becomes dispensable for the spread of Salmonella in the tissues. Conversely, when an active Phox is present, a SPI-2 T3SS mutant grows inside cells to high intracellular densities but appears to be unable to escape from the cells and disseminate in the body.

Dr Grant said: "Salmonella is a significant public health threat. Unfortunately, effective treatments and vaccinations have thus far eluded scientists, in part because of a lack of understanding of how and why the bacteria spread. This research provides critical insight which will hopefully lead to new medical interventions for this disease."


Story Source:

The above story is based on materials provided by University of Cambridge. The original story is licensed under a Creative Commons license. Note: Materials may be edited for content and length.


Journal Reference:

  1. Andrew J. Grant, Fiona J. E. Morgan, Trevelyan J. McKinley, Gemma L. Foster, Duncan J. Maskell, Pietro Mastroeni. Attenuated Salmonella Typhimurium Lacking the Pathogenicity Island-2 Type 3 Secretion System Grow to High Bacterial Numbers inside Phagocytes in Mice. PLoS Pathogens, 2012; 8 (12): e1003070 DOI: 10.1371/journal.ppat.1003070

Cite This Page:

University of Cambridge. "New study sheds light on how Salmonella spreads in the body." ScienceDaily. ScienceDaily, 6 December 2012. <www.sciencedaily.com/releases/2012/12/121206203411.htm>.
University of Cambridge. (2012, December 6). New study sheds light on how Salmonella spreads in the body. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2012/12/121206203411.htm
University of Cambridge. "New study sheds light on how Salmonella spreads in the body." ScienceDaily. www.sciencedaily.com/releases/2012/12/121206203411.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins