Controlled phage therapy hints at future alternative to antibiotics
Phages, viruses that thrive by infecting bacteria, have long been mooted as a potential replacement for antibiotics. But where antibiotics pose the problem of the bacteria they target mutating into dangerous resistant strains, phages pose risks due to their own fast-paced evolution, though those risks are poorly understood.
But new research suggests it may be possible to mitigate those risks. Left to nature, particular phages are able to seek out and destroy particular types of bacteria. But here it’s only the seeking that the researchers are interested in, using the phages to deliver a payload of gold nanorods which, with the help of light, destroy both the target bacteria and their phages at once. If you’ll forgive the grim analogy, you can think of the phage as the guidance system and the nanorods the warhead of this particular antibacterial guided missile.
“What we did was to conjugate the phages to gold nanorods,” UC Santa Barbara’s Irene Chen explains in a press release. If you thought conjugation was something that happened only to verbs, don’t panic: it can also simply mean to join or couple. “When these nanorods are photo-excited, they translate the energy from light to heat, and that creates very high local temperatures.”
The so-called “phanorod” combinations of nanorods and phages were added to in-vitro cultures of mammal cells with an added bacteria biofilm. They were then exposed to light in near-infrared wavelengths to cause the all-important photo-excitement. The resulting heat kills both the bacteria and the phage.
In experiments, the phanorods successfully destroyed the potent human pathogens E. coli, P. aeruginosa and V. cholerae. It’s important to note that the phanorods also destroyed 20 percent of the mammal cells in the culture, which the research categorizes as a “low rate of damage.”
“This issue of whether it damages mammalian tissues is very important,” Chen explains. “Work in nanotechnology and nanomedicine treating bacterial infections indicates that when it’s non-targeted, it really does burden the surrounding tissues.”
As well as the unpredictable nature of unchecked phage evolution, there are other issues with their historical use. They can potentially carry toxins, and it’s hard to gauge the success of the treatment. “You might see it completely work or you might see it completely fail, but you don’t have the kind of dose response you want,” Chen explains. But this new controlled approach to phage therapy could potentially mitigate these issues as well.
The team’s research will go on to look at more phages to target more types of bacteria, as well as exploring photothermal methods to treat several bacterial infections at once. However, the work is very much at the research stage, and there’s no suggestion of clinical use at this stage.
The team’s research was published Monday in Proceedings of the National Academy of Sciences. It’s free to read online.