Bacteria and other pathogens often enters the body at mucosal surfaces, which line body cavities that are exposed to the environment. Among the microbes that take residence in these surfaces are small viruses known as bacteriophages, which infect and kill bacteria. But the role that such viruses play in defending their host against infection has remained undocumented, until now.
In a paper published in the Proceedings of the National Academy of Sciences (1), the team describes a new Bacteriophage Adherence to Mucus (BAM) model and suggests that this phage-host relationship is one of the first examples of a symbiotic relationship between phage and metazoan host.
“We’re kind of proposing that this is a new novel immunity that’s non-host derived,” said Jeremy Barr, the paper’s lead author and a post-doctoral research fellow in the lab of SDSU biology professor Forest Rohwer. “This is to our knowledge one of the first examples of a direct symbiosis between a phage and an animal.”
The phages stick to mucosal sites through protein manes on their capsids that are similar to immunoglobulins. The group found that these immunoglobulin-like proteins bind to sugar residues in the mucus so that the phage can embed itself in the mucosal layer.
“The idea is novel and quite attractive,” said Fredrick Bushman, professor of microbiology at the University of Pennsylvania who was not involved in the study. “It makes sense that metazoa and phage would co-evolve so that phage were concentrated at the same surface sites as bacteria, thereby allowing the phage to access their prey efficiently and the host to block bacterial infection…I bet many laboratories will design experiments to follow up on these ideas.”
During previous studies of coral reef systems, Rohwer and his lab first noticed a substantial increase in phage concentration on mucosal surfaces compared to the surrounding cellular environment.
To follow-up, the team collected mucus samples from a diverse range of systems, including coral, fish, mice, and humans. They then counted the phage-to-bacteria ratio in the samples using fluorescent DNA stains and epifluorescence microscopy. In their analysis, the group found an increased phage-to-bacteria ratio on the mucosal surfaces that they sampled compared to the surrounding environment.
“Since then, we knew this was something that was actually happening in nature, and there was definitely an increase in all these all these really diverse mucus,” Barr said. “That was kind of a starting point.”
Then the group used a well-known phage model system, bacteriophage T4, and cultured cells to further test the phage’s dependence on the mucosal layers. They compared two human lung cell populations: one that produced a mucus layer and one that was modified to not produce a mucus layer.
After incubating the cells with Escherichia coli, the researchers found that the phage protected the mucus-producing cells from cell death. In contrast, cultured cells that did not have a mucosal layer for the phage to stick to a cell death rate 3 times that of unmodified cells after 12 hours.
The research may potentially lead to therapeutic breakthroughs in treatment for Escherichia coli and other gastrological infections. “There’s been a lot of these pathogenic E. coli outbreaks in the last couple years,” said Barr. “There could definitely be a prophylactic treatment in a phage therapy angle that we could work towards.”
- Barra, J.J., R. Auroa, M. Furlana, K.L. Whitesona, M.L. Erbb, J. Poglianob, A. Stotlanda, R. Wolkowicza, A.S. Cuttinga, K.S. Dorana, et al. 2013. Bacteriophage adhering to mucus provide a non–host-derived immunity. PNAS Early Edition. 10.1073/pnas.1305923110