Saturday, June 02, 2007

MDR mobility

There is much talk in the blogsphere about this idiot who knowingly exposed a huge number of people to a multi drug resistant strain of TB. f you are interested, Tara Smith over at Aetiology has several posts (1,2,3 & 4 so far) on the topic including links to other discussions and information.

Instead of commenting on that situation I thought I'd call attention to a recent paper by Tim Welch and others in Plos One about a plasmid inferring multi drug resistance that has been found to be present quite common in our food supply.

This plasmid is of concern because it was isolated from a strain of the plague bacteria, Yersinia pestis, back in the mid 1990s. Since then it has not turned up in Y. pestis again but this new paper reports finding related plasmids in the fish pathogen Yersinia ruckeri and in a strain of the food born pathogen Salmonella. The picture on the left shows the relationship between the three plasmids.

The inner circle shows the conserved backbone indicating that the plasmids isolated from three different species of bacteria have a recent, common origin. They all have the genes necessary to be self mobilizing but they differ in the number of drug resistance genes they carry, ranging from 9 to 13.

using data from the conserved backbone Welch et al. screened a large number of MDR strains of Salmonella, E. coli and Klebsiella sp. isolated from agricultural products and found that the majority of the resistant strains harbor a relative of this plasmid.

From the paper:
The discovery of these MDR IncA/C plasmids in evolutionarily distinct pathogens attests to recent genetic exchange, either directly between these bacterial species or through bacterial intermediates, and it suggests that overlap in the ecological niches of these organisms is sufficient to permit past or future plasmid transmission.

we present evidence that a common plasmid backbone is prevalent among E. coli, Klebsiella sp. and multiple Salmonella serotypes isolated from retail meats in the US, and among some food animal isolates of E. coli. Our data imply that high levels of MDR in the causative agent of plague may rapidly evolve naturally...


Dave said...

Hey Andrew. I've been thinking about this and should really check the paper again, but to what extent do the resistance genes overlap with antibiotics commonly used in agriculture? I think a pattern is emerging, and has sound theoretical underpinnings, but given the economic stake in antibiotics in animal feed, there's a need for really unassailable data before anyone will move on it.

amstar said...


This is the list of determinants found on the plasmids:
sulfonamides (sul1, sul2);
phenicols (cat, floR);
tetracyclines (tetRA);
aminoglycosides/aminocyclitols (aacC, aadA, aphA, strAB);
quaternary ammonium compounds (qacEdelta1, sugE1, sugE2);
β-lactams (blaCMY-2-1, blaCMY-2-2, blaSHV-1);
trimethoprim (dhfrI);
mercury ions (merRTPABDE, merRTPCADE)

According to this publication from the USDA, sulfonamides, tetracyclines, aminoglycosides, and β-lactams are among the antibiotics approved for either disease prevention or growth enhancement.

I understand powerful political pressures exist that would resist any moves to restrict antibiotic use, but how else did all of these genes get so widespread if not by selective pressures associated with antibiotic use. It is a big plasmid there must be some cost to carrying it around, right? What additional information do you think is needed to make the data unassailable?

Innocent bystander said...

The plasmid is obviously emergent as a result of environmental stimuli (i.e., antibiotic use for therapy/growth promotion). The questions are 1) the risk to human health because these resistances target animal drugs that mostly do not resist commonly used human drugs; 2) whether these plasmid would go away with cessation of antibiotic use or if the will stay in populations regardless; and 3) what is the risk of transfer of these plasmids to other bacteria (from the publication here and others in Pubmed it seems inevitable that they IncA/C plasmids are readily transferred to a variety of hosts.