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NYU Researchers Find Viruses Can Transfer Toxin Genes Between Bacterial Species

NEW YORK (GenomeWeb News) – Bacterial genes can be transferred as quickly between some bacteria of different species as they can within the same species, according to a paper in today’s issue of Science.
Phages, viruses that infect bacteria, usually infect only closely related bugs. But a duo of New York University researchers showed that genetic regions housing super-antigen genes and other mobile elements — called pathogenicity islands — could be transferred between Staphylococcus aureus and another species, Listeria monocytogenes. Based on their results, the authors urged caution about the use of phage-mediated therapies in settings in which these and other gene-swapping bacteria co-occur.
“[P]hages may participate in a far more expansive network of genetic information exchange among bacteria of different species than originally thought, with important implications for the evolution of human pathogens,” co-authors John Chen and Richard Novick, researchers from New York University’s Kimmel Center for Biology and Medicine, wrote.
Many viruses that infect bacteria take bits of bacterial DNA with them as they move from one bacterial cell to another. But since these so-called transducing phages tend to parasitize groups of closely related bacteria, researchers traditionally thought this sort of genetic exchange occurred mostly within bacterial species. Even so, Chen and Novick reasoned, it is possible that phages contribute to more widespread genetic exchange between bacteria.
The pair addressed this possibility by looking first at S. aureus pathogenicity islands, or SaPIs — genetic elements specialized for phage-mediated transfer between bacteria. The SaPIs, 14 to 18 thousand base elements, code for mobile elements, including superantigens. Among them: the gene coding for the toxic shock toxin.
“Although they are ubiquitous among S. aureus strains, the SaPIs are extremely rare in non-aureus staphylococci and have yet to be described in other bacterial genera, despite their great mobility,” the authors noted.
For the latest study, the researchers investigated the sequence specificity of the SaPI insertion site by making a deletion in the site and looking at whether the modified strain could still take up an SaPI derivative. Indeed, they found that a phage called 80α could transfer the SaPI to the deletion strain with about the same transfer frequency observed in the normal parental strain.
These SaPI integrations often occurred at secondary sites in the genome and involved crossover events mediated by an enzyme called integrase, they found. The SaPI integrase also seemed to require lower sequence specificity than other integrases, making it more likely that SaPIs would be able to be taken up by species beyond S. aureus.
“The frequency and variability of secondary sites in S. aureus increases the probability that suitable insertion sites are present in many bacterial species, and any bacterium that can absorb SaPI helper phage is a potential recipient,” the authors reasoned.
To test this, the researchers looked at a variety of Gram-positive bacteria to see whether they could take up modified SaPI. Within the Staphylococcus genus, the researchers found that S. xylosus could take up SaPI derivatives. The researchers noted that rare SaPI transduction to both S. xylosus and S. epidermidis has been reported in the past.
When they looked at other genera, the researchers found that Listeria monocytogenes was the only non-staphylococci bug tested that took up SaPIs, whereas SaPIs did not transfer to several other species, including Bacillus subtilis, Salmonella enterica, and Streptococcus pyogenes.
The efficiency and frequency of the pathogenicity island transfer to L. monocytogenes was also unexpected: the SaPIs were transferred to L. monocytogenes almost as often as they were to S. aureus. The researchers found that several other mobile elements — and several SaPI helper phages — were also transferred efficiently to L. monocytogenes.
For instance, Chen and Novick found that they could transfer a modified virulence factor inserted into the Panton-Valentine leukocidin, or PVL, locus of a detoxified phage to L. monocytogenes — a result the duo called “disconcerting,” given PVL’s potential role in some staphylococcal diseases.
Because S. aureus and L. monocytogenes can be found in cow’s milk and can both contribute to an udder inflammatory condition called bovine mastitis, the researchers decided to test whether phage-mediated SaPI transfer occurred in milk. Indeed, the researchers found evidence for spontaneous prophage-mediated transfer of the SaPIs SaPI1 and SaPIbov1 between S. aureus and L. monocytogenes strains co-cultured in raw milk.
And, the researchers noted, such results may have real world implications, since phage therapy is currently being explored as an avenue for treating the S. aureus infection behind bovine mastitis. Based on Chen and Novick’s experiments, phage treatments may clear S. aureus strains but may also lead to SaPI transfer to L. monocytogenes. That suggests care should be taken to avoid phage treatments that inadvertently introduce SaPI and other potential mobile elements into new bacterial strains, the authors noted.
“Although superantigen-producing L. monocytogenes strains have not yet been reported,” they cautioned, “it is certainly true that environmental isolates of S. aureus carrying SaPIs are ubiquitous. Thus, the widespread used of anti-aureus phages in agriculture may accelerate the spread of staphylococcal toxins to Listeria or to any other bacteria to which the phages can adsorb.”