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Virulence Factor Transfers among Enterococci Suggest Risk for Probiotics 

Bacteria have been processing food for humans at least since farmers learned very early on to make cheese and yogurt. Although food safety issues seem to be in constant ferment, fresh concerns over the enterococci—several of which are used for starter cultures for cheeses and yogurts as well as in probiotic preparations and “functional foods”—are emerging. Several factors contribute to those concerns, including the broadening presence in foods of these erstwhile nosocomial pathogens and the prevalence of multidrug resistance among them.

 “Enterococci rank in the top three of all [pathogens causing] hospital-acquired infections in the U.S., accounting for more than 800,000 cases per year, at an estimated cost of $500 million,” says Judith A. Kjelstrom, associate director of the Biotechnology Program at the University of California, Davis. These bacteria “are a leading epidemiologic reservoir for the genesis of serious and life-threatening infections involving the intra-abdominal cavity and bloodstream  and also are responsible for many urinary tract infections . . . It should be noted that infections are not caused by indigenous microbes, but are acquired from the hospital environment. It is not understood how these enterococci take over the colon and move the commensals aside.”

Until recently, little was known about the critical differences between strains that are safe for use in foods and those that are not. However, virulence factors can be transferred among such strains, enabling some of those used in the food industry as starter cultures to acquire virulence factors in vitro from strains isolated as nosocomial pathogens in clinical settings, according to Michael J. Gasson and Tracy J. Eaton of the Institute of Food Research, Norwich, United Kingdom, who report their findings in the June issue of Applied and Environmental Microbiology (65:1628-1635). The U.K. Food Standards Agency sponsors their research, which is intended to place the scientific basis for this evaluation on firmer footing under food safety regulations developed under the auspices of the European Community. 

Gasson and Eaton find that Enterococcus strains that are being used in the food industry carry genes encoding several types of pheromones, which can serve as virulence factors. Other types of virulence factors include compounds that endow bacteria with properties such as hemolysin- or cytolysin-producing capacity, resistance to phagocytosis, and adhesiveness.

Ominously, these enterococcal pheromone genes are associated with plasmids that carry a high likelihood of spreading antibiotic resistance along with virulence determinants. “The pheromone-responsive plasmids of Enterococcus faecalis, which encode the virulence factor called aggregation substance, also carry antibiotic resistance determinants,” says Kjelstrom. “Emergence of vancomycin-resistant and multidrug-resistant strains of [Enterococcus] is a worldwide health concern.” Because vancomycin is often the antibiotic of last resort in cases of multidrug resistance involving infections caused by the enterococci, “this is a very important food safety issue,” she says. 

Despite these risky prospects, the starter strains being used in the food industry, when tested, contain fewer virulence determinants than do isolates from foods, which, in turn, contain fewer such determinants than do clinical isolates obtained from patients, according to Gasson and Eaton. Moreover, apparently no single virulence factor in Enterococcus by itself can convert a harmless strain into a pathogen. “If you are going to put new Enterococcus strains into the food chain you need to be pretty cautious in assessing the possible safety concerns,” says Gasson. 

“We haven't asked what the effect of [transfer of virulence determinants from medical isolates] is on the virulence of the food strain,” Gasson continues. “We need to do challenge experiments before and after acquisition. But imagine you consumed 10¹¹ cells of a safe strain, and that there existed among your commensal bacteria a small population of Enterococci with virulence determinants.” The health risk is that those determinants could spread from the small population into the far greater numbers of food- or probiotics-borne enterococcal bacteria—enabling them to cause infectious havoc.  

“Why take the risk?” asks Kjelstrom. “It goes against common sense to use this organism since we have so many lactic acid bacteria to choose from.” However, advocates of using Enterococcus in foods have built a thriving probiotics business around this microbe, with some of them claiming that Enterococcus-based cultures are superior to those that use lactobacilli.

Normally healthy individuals are probably not particularly vulnerable to such still-hypothetical virulence transfer events involving food and commensal strains of Enterococci, whereas those whose immune systems are already compromised might well be, says Abigail Salyers of the University of Illinois, Champaign-Urbana. “If it proves to be true that Enterococcus strains in food have the potential to cause infection in certain people, then people with those predisposing conditions should be warned against the consumption of foods that carry Enterococcus.”

David Holzman 
David Holzman is a freelance science writer in Lexington, Mass.