Cells of Salmonella enteritidis change
shape as they grow. This scanning
electron micrograph shows a
mixture of small cells with
filaments and very large cells
that lack filaments. Small
cells arise only during certain
growth stages and efficiently
contaminate eggs when the
time is right.
Antibiotics were once called miracle drugs because they revolutionized
treatment of disease, curing bacterial infections that used to lead
to debilitation and, all too often, death. Not only humans, but also
livestock and pets have benefited from these wonder drugs. But over
the years, some bacterial pathogens have developed resistance to the
antibiotics that once spelled their doom.
Agricultural Research Service
scientists in Athens, Georgia, are working to learn which pathogens
are resistant in livestock, determine why and how they became resistant,
and find ways to turn back the tide. All the while, bacteria continue
to do what they do bestadapt in order to survive.
Recently, resistance has been observed in bacteria known to cause plague
and in Staphylococcus aureas, a common agent in wound
and blood infection. When bacteria became resistant to only one or two
antibiotics, there was never a concern, since pharmaceutical companies
kept a steady stream of new drugs coming our way. This changed dramatically
when pathogens developed resistance to more and more of the drugs. Today,
there are fewer new antibiotics being developed, and we face the challenge
of finding new ways to treat diseases and infections we once thought
The Chase Is Afoot
When confronted with emerging resistance to antibiotics, also called
antimicrobials, several U.S. government agencies began to research and
monitor the problem. In 1996, programs conducted by the U.S. Department
of Agriculture (USDA), the Centers for Disease Control and Prevention
(CDC), and the Food and Drug Administration (FDA) were coalesced into
the National Antimicrobial Resistance Monitoring System (NARMS). USDA
leads the animal arm, CDC leads the human arm, and FDA leads the retail
USDA's research component dedicated to this project is the ARS Antimicrobial
Resistance Research Unit, in Athens. Led by microbiologist Paula Fedorka-Cray,
the team is currently testing for and characterizing antimicrobial resistance
in four bacteria: non-typhoid Salmonella, Campylobacter,
generic Escherichia coli, and Enterococcus species. The
bacterial samples tested in the animal arm of NARMS are obtained from
three sources: diagnostic samples taken from sick animals in which treatment
history is presumed but not confirmed, on-farm samples from healthy
animals, and slaughter/processing samples from federally inspected plants.
The lab's scientists isolate, test, and characterize more than 17,000
bacterial isolates per year.
To Each Its Own
It would be simple and convenient if all bacteria reacted predictably
and uniformly to treatment with antimicrobials. Unfortunately, nothing
could be further from the truth. For instance, there are many different
types of Campylobacter. Two of the most common types that cause
illness in humans are C. jejuni and C. coli. Each responds
differently to antimicrobials, and C. coli appears to become
resistant to them faster than C. jejuni. Both have demonstrated
resistance to one of the newest classes of antimicrobialsfluoroquinolones.
Used in human medicine since the 1980s, fluoroquinolones were approved
for use in chickens in 1995. Since then, microbiologist Mark Englen
of the Athens team has been studying and tracking Campylobacter
resistance to these drugs.
Another potentially harmful bacterium, Salmonella, has more
than 2,400 different serotypes, and each one appears to develop resistance
to antimicrobials at a different rate. One type of Salmonella
that most often sickens both humans and other animals is S. typhimurium.
It appears to easily acquire resistance to multiple antimicrobials.
Some strains are now resistant to 13 of 17 antimicrobials tested. Of
all Salmonella types tested from 1997 to 2003, the rate of single-drug
resistance has remained relatively stable at 9.5 percent of the samples.
But Salmonella that are resistant to more than five drugs rose
from 11 percent to 20 percent. And those that are resistant to more
than 10 drugs rose from a scant 0.8 percent to almost 6 percent.
Low-temperature electron micrograph
of a cluster of E. coli bacteria. Each
individual bacterium is oblong shaped.
"The problem is quite clear," says Fedorka-Cray. "More
than 35 percent display resistance to one or more antibiotics. Unfortunately,
there is a finite number of antibiotics, and Salmonella continues
to alter to give itself the greatest chance of survival." Jonathan
Frye, a microbiologist who studies resistant Salmonella in Athens,
has developed new molecular technology that may provide a more accurate
analysis of resistance and the genetics behind acquisition of resistance.
Tangled Web of Transmission
Controlling resistance starts with understanding how it develops and
how bacteria move throughout the ecosystem.
"Antimicrobial use in livestock production can result in resistant
bacteria that can be passed to humans via the food chain, and our team
is studying how and with what frequency this occurs," says Fedorka-Cray.
Meat can also become contaminated during processing, and fruits and
vegetables can pick up bacteria from the manure used to fertilize them.
"Resistance can also develop when a human or a pet is prescribed
an antimicrobialespecially when it's used inappropriately or improperly.
Since any use of antimicrobials may result in selection of resistant
bacteria, these drugs should only be used when necessary," Fedorka-Cray
says. And, she adds, "Since food can be a transmission vehicle,
it is important for people to handle foods correctly, cook food thoroughly,
and always thoroughly wash their hands and food-preparation areas."
Still, some bacteria harbor resistance even though they haven't been
exposed to manmade antimicrobial drugs, she says. This is called "intrinsic
Fedorka-Cray's group has developed the nation's largest descriptive
database of resistant populations of bacteria recovered from animals
over time. "The data help us determine the probability that resistance
will occur or be maintained if antimicrobials are used," she says.
"When you reduce use of antimicrobials, you may reduce prevalence
of resistant organisms. On the other hand, some swine studies have shown
that eliminating antimicrobials does not eliminate resistant bacteria.
This may mean that bacteria have become permanently resistant to some
antimicrobials as a survival tool." Scientists face many such challenges
as they try to determine how to decrease numbers of resistant bacteria.
Microbiologist Charlene Jackson of Athens is focusing her research on
Enterococcus species, bacteria commonly found in nature but particularly
problematic in hospitals.
Changes in antimicrobial use in food-animal production are being made.
"Until recently, the pattern of antimicrobial use on farms changed
very little. Now, veterinariansas well as physicians and those
in related fieldsare reassessing how and when they use antimicrobials.
Today's production systems may not need the same level of antimicrobial
use or may be able to eliminate the use of certain antimicrobials altogether,"
says Fedorka-Cray. "The good news is that we have never reached
a situation where an entire bacterial population isolated from animals
is resistant to all known antimicrobials."By Sharon
Durham, Agricultural Research Service Information Staff.
This research is part of Food Safety (Animal & Plant Products),
an ARS National Program (#108) described on the World Wide Web at www.nps.ars.usda.gov.
Paula Fedorka-Cray is
in the USDA-ARS Antimicrobial Resistance Research Unit, Richard
B. Russell Research Center, 950 College Station Rd., Athens, GA
30605; phone (706) 546-3305, fax (706) 546-3066.
"Detectives Search for Antimicrobial-Resistant Organisms"
was published in the March
2005 issue of Agricultural Research magazine.