An Infectious Agent of Deception, Exposed Through Proteomics

Sep 29, 2006

Salmonella bacteria, infamous for food poisoning that kills hundreds of thousands worldwide, infect by stealth. They slip unnoticed into and multiply inside macrophages, the very immune system cells the body relies on to seek and destroy invading microbes.

Just how Salmonella escapes detection by macrophages, turning predator cells to prey complicit in promoting infection, has seemed impossibly complicated, a needle-in-a-haystack proposition involving thousands of proteins, the building blocks that carry out cells’ vital functions.

Applying the high-volume sorting and analytical power of proteomics—a detailed survey of microbial proteins present in the 24 hours that follow mouse-macrophage infection—a team led by Liang Shi of the Department of Energy’s Pacific Northwest National Laboratory in Richland, Wash., has turned up a suspect protein.

The discovery of the protein, dubbed STM3117, is detailed today (Sept. 29) in The Journal of Biological Chemistry. Knocking out the gene that codes for STM3117, the researchers subsequently crippled the microbe’s ability to multiply inside macrophages. Shi and colleagues say the protein and two closely related proteins discovered in the study are similar in genetic sequence to those known to make and modify chemicals in the microbe’s cell wall called peptidoglycan.

Drug and vaccine designers armed with this mouse-model information can target chemicals or immune responses that disrupt peptidoglycan synthesis and other processes linked to Salmonella’s colonization of macrophages in humans, said Joshua Adkins, a co-author on Shi’s paper and lead author of a related study in Molecular & Cellular Proteomics last month. A quick identification of these proteins, Adkins added, could help physicians assess the virulence of a given strain.

The candidate proteins were winnowed from among 315 possibilities that emerged through a combination of techniques, culminating in measurements by Fourier-transform mass spectrometry, or FT-MS. A suite of FT-MS instruments customized by co-author and PNNL-based Battelle Fellow Richard D. Smith enabled the team to rapidly separate and identify many proteins at once even as macrophages were being infected.

Most of the initial candidates were designated “house-keeping” proteins, or those whose numbers relative to other proteins remained more or less constant during the course of infection. But 39 proteins shot up in number during bacterial colonization of macrophages, and of those, a handful or so—including STM3117—responded specifically to a macrophage protein associated with resistance to microbial infection. A standard assay called Western blot confirmed the abundance increases of that small group of proteins during infection.

Source: Pacific Northwest National Laboratory

Explore further: Native vegetation makes a comeback on Santa Cruz Island

add to favorites email to friend print save as pdf

Related Stories

New tool identifies therapeutic proteins in a 'snap'

Aug 21, 2014

(Phys.org) —In human and bacterial cells, glycosylation – the chemical process of attaching complex sugar molecules to proteins – is as fundamental as it gets, affecting every biological mechanism from cell signaling ...

A secret to making macrophages (w/ Video)

Jul 18, 2013

Biologists at the California Institute of Technology (Caltech) have worked out the details of a mechanism that leads undifferentiated blood stem cells to become macrophages—immune cells that attack bacteria ...

Revealing camouflaged bacteria

Apr 16, 2014

A research team at the Biozentrum of the University of Basel has discovered an protein family that plays a central role in the fight against the bacterial pathogen Salmonella within the cells. The so cal ...

Recommended for you

Transparent larvae hide opaque eyes behind reflections

5 hours ago

Becoming invisible is probably the ultimate form of camouflage: you don't just blend in, the background shows through you. And this strategy is not as uncommon as you might think. Kathryn Feller, from the University of Maryland ...

Peacock's train is not such a drag

6 hours ago

The magnificent plumage of the peacock may not be quite the sacrifice to love that it appears to be, University of Leeds researchers have discovered.

Iberian pig genome remains unchanged after five centuries

11 hours ago

A team of Spanish researchers have obtained the first partial genome sequence of an ancient pig. Extracted from a sixteenth century pig found at the site of the Montsoriu Castle in Girona, the data obtained indicates that ...

User comments : 0