Fey highlights MRSA, discusses antibiotic-resistant bacterial species
In the last several years, use of antibiotics in food animals has become the target of many, who blame antibiotic use for the creation of “superbugs.”
“I want to tell producers a microbiological story that population geneticists and biologists are throwing around different ideas for how livestock-associated MRSA is developing and evolving,” comments Paul Fey, director of the Clinical Microbiology Laboratory at the University of Nebraska Medical Center. “It is a different story than we have heard so far.”
MRSA, Fey explains, is methicillin-resistant Staphylococcus aureus, and the bacterium has a long history.
Advent of antibiotics
Before 1941, Fey notes that antibiotics weren’t available.
“If we look at the mortality rate of staphylococcal bacteria prior to 1941 – the pre-antibiotic era – we saw a mortality rate of 82 percent,” he says. “The causes of disease showed cases where people were getting a splinter, coming down with staphylococcal bacteria and dying.”
When penicillin was discovered and put into use, the staphylococcal bacteria begin to resist penicillin.
“Penicillin is the best antibiotic we can use against Staphylococcus aureus, but most of the bacteria have resistance,” Fey says. “To combat that, pharmaceutical companies made methicillin.”
Methicillin is a penicillin-like antibiotic with a slight change in the structure of the drug, allowing it be to be effective against the bacteria.
“The change of a side chain to make methicillin made the staph not resistant,” Fey explains. “Methicillin was used from the 60s until the present day.”
MRSA is able to resist the antibiotic and cannot be killed by traditional methods.
“At the University of Nebraska Medical Center, about 45 percent of our bacterial isolates are resistant to methicillin, and 95 to 97 percent are resistant to penicillin,” Fey comments.
Staphylococcus aureus is a highly significant bacterium of today, notes Fey, adding that it has a wide variety of defense mechanisms.
“S. aureus is a well-armed pathogen and is interesting to study,” he continues. “It causes a wide variety of different infections in a variety of organisms.”
Fey notes that the bug may result in problems ranging from respiratory infections to osteomyelitis, endocarditis and an array of toxin-mediated diseases, among others.
“It is also a significant cause of food poisoning and causes a variety of different types of skin and soft tissue diseases,” Fey says, adding that the bacteria can be very serious. “Right now, it is the most common cause of endocarditis, nosocomial infections, or infections originating in hospitals, and soft tissue infections.”
Fey additionally notes that methicillin is no longer the antibiotic of choice for use against staphylococci, but rather, similar antibiotics are utilized.
Until 1999, Fey says that it was believed MRSA existed only in hospital-type situations.
However, Native American and Native Alaskan communities started to see high rates of MRSA, even though they had no contact with healthcare facilities.
“It was very different than what we had seen before,” Fey explains. “Then, a particular strain of the bacteria called USA300, a major community-acquired strain in the U.S., was isolated from companion animals.”
The question, Fey asks, is what makes the USA300 strain special and able to colonize both humans and animals.
“We don’t really know what is important about USA300, but we do have some important hypothesis about the strain,” he continues.
“This particular strain also has a new gene called a genomic island,” Fey says. “That island is called the ACME island, and it is thought to confer an increased ability of the organism to colonize skin.”
The ability of the bacteria to colonize skin increases its ability to transfer between individuals.
Other organisms already have the ability to infect multiple species, including food animals, says Fey, and some can cause disease in both humans and animals.
“The strain ST398 started when the research enterprise became associated with MRSA in food animals,” he says. “Unfortunately, it has the capability to colonize and cause disease in humans, as well.”
However, the strain is unique in that it can’t be passed from human to human.
“If we look at pig farms with the ST298 strain of Staphylococcus aureus, there is an increased risk of infection for the person working with the pigs,” he says. “However, they don’t typically transfer it to other members of the family.”
“Originally, humans transferred it to pigs,” he says.
Though the strain is thought to have originated in humans, it picked up the resistance to methicillin and other antibiotics while in swine populations.
“We also found that once we have strains that re-infect humans from pigs, they have changed a bit,” Fey comments. “When we analyze those strains, they have picked up other human-specific virulence factors.”
“When it is transferred back to human populations, it is picking up extra virulence factors that allow it to cause disease,” he notes. “The propensity of Staph aureus to acquire new genes allows it to cause disease in humans and animals.”
“We know we have situations where animals can transfer Staphylococcus aureus to humans, and we have examples where humans have given Staphylococcus aureus to food animals,” Fey comments.
He also notes that there are areas where research must continue to understand MRSA and antibiotic resistance further.
“I think there are other selective pressures in play here,” Fey says. “I think we really need to look at what selective environments are allowing the selection to occur.”
Fey continues, “There are a lot of really interesting biological factors in play.”
Bacteria become resistant to antibiotics by acquiring genetic material from other resistant bacteria. Bacterial DNA is present on small rings known as plasmids. Plasmids can be transferred between bacteria in a number of ways.
“Penicillin, methicillin and cephalosporins are all beta-lactam antibiotics,” Paul Fey, director of the Clinical Microbiology Laboratory at the University of Nebraska Medical Center, explains. “The beta-lactam antibiotics work by binding enzymes to the cell wall of bacteria and not allowing bacteria to build their cell wall anymore. As the cell grows, it bursts, killing the bacteria.”
However, the plasmids contain a gene called MECa, which allows the bacteria to hydrolyze the beta-lactam antibiotics and negate their ability to function.
“Methicillin resistance is transferrable,” Fey says.