By Phil Williams
University of Georgia
Scientists may need to reexamine assumptions about the spread
of antibiotic-resistant genes, according to a new study by
researchers at the University of Georgia.
They found that poultry litter -a ubiquitous part of large
broiler operations – harbors a vastly larger number of microbial
agents that collect and express resistance genes than was
previously known.
The study, published April 20 in the Proceedings of the
National Academy of Sciences, shows that waste left behind by flocks
raised in industrial chicken houses is rich in genes called
integrons that promote the spread and persistence of clusters of
varied antibiotic resistance genes.
Solving long-standing puzzle
“We were surprised to find a vastly greater pool of these
multi-resistance clustering agents than anyone had suspected
before,” said Anne Summers, a UGA microbiologist who led the
study. “Finding such a huge reservoir of integrons explains a
long-standing puzzle about how clusters of resistance genes
spread so rapidly and persist in bacterial communities even after
antibiotic use concludes.”
Other authors of the paper included Sobhan Nandi, a
postdoctoral associate in the UGA department of microbiology, and
John Maurer
and Charles Hofacre of the department of avian medicine in UGA’s
College of Veterinary Medicine. Maurer also holds an appointment
with the UGA College of Agricultural and Environmental Sciences’
Center for Food Safety in Griffin.
Antibiotic resistance is a serious and growing problem for farm
animal operations and human health. Antibiotic use to treat
disease and increase feed efficiency has been a common part of
industrial farms for more than half a century.
When antibiotic-resistant bacteria began to show up in hospitals
in the 1950s, researchers initially believed that simply
restricting the use of antibiotics on farms could reduce the
prevalence of antibiotic resistance among humans.
“Over the past 30 years, we have learned this hope was
unrealistic because we share both pathogenic and benign bacteria
with other humans and animals,” said Summers, “and because
bacteria transfer genes among themselves.”
Samples takens from Georgia poultry houses
At the heart of the multi-resistance problem are integrons,
which scientists until now have exclusively studied in such
pathogenic
bacteria as Salmonella and E. coli.
The UGA team wondered, however: Does the poultry production
environment also harbor integrons that assemble these large
clusters of distinct resistance genes?
To find out, samples of poultry litter from Georgia broiler
houses were collected regularly over a 13-week period. Litter
begins as a bedding material of softwood shavings placed in
commercial broiler houses before chicks are brought to it. By the
time the flock is harvested, the shavings have become mixed with
chicken feces, uric acid, skin, feathers, insects and small
invertebrates. Rich in minerals, poultry litter is often recycled
for fertilizer and other uses.
What the researchers discovered was startling: One integron type,
called intl1 (typically found in E. coli and Salmonella) was up
to 500 times more abundant than these bacteria themselves were in
litter. A bit of microbial sleuthing revealed that integrons are
also carried by so-called Gram positive bacteria that are much
more abundant in litter than the E. coli-type bugs, called Gram
negative bacteria.
“The fact that integron genes in the Gram positive bacteria
are identical to those of E. coli indicates they are being
actively
exchanged among these otherwise unrelated bacteria,” said
Summers. “Just as intriguing, integrons and resistance genes were
abundant regardless of antibiotic use on the farms, suggesting
that, once acquired, integrons are inherently stable, even
without continual exposure to antibiotics.”
The study has several significant implications, said Summers.
Most studies of antibiotic resistance have been done in hospital
settings, and until recently, much less work has been done on the
real-world ecology of systems that create
multiple-resistant clusters. Knowledge about how antibiotic
resistances
spread from animals to humans is at present sketchy; however,
since humans and their pets are “colonized” by similar bacteria,
it is reasonable to think we and our companion animals also
harbor such multi-resistance gene clusters that are enriched when
we take an antibiotic ourselves or treat our pets.
Integrons are the key to the problem
Humans and animals have billions of bacteria in and on their
bodies at any time, and even if resistance to a single antibiotic
arises in a few of them through mutation, there are still several
other antibiotics that can eliminate them. But if bacteria in the
same environment are already equipped with clusters of genes
conferring resistance to many antibiotics and can readily
exchange these clusters, then the treatment options are limited.
“That’s what we have today, and the surprising abundance of
integrons in the environment is a key as to why we have this
problem,” said Summers.
The discovery is now leading Summers and her UGA colleagues to
see whether these resistance-gene-clustering systems are present
in previously unrecognized reservoirs in companion animals and
humans. The results will change our understanding of where
resistance to new antibiotics will develop and how fast and how
far it will spread and have implications for all antibiotic use,
not just that in agriculture.
The research was supported by a grant from the National
Research Initiative of the U.S. Department of Agriculture and made
possible by four anonymous poultry producing companies that
afforded free access to their facilities for sample collection.
