The Scientist - USA (2021-02)

© LISA CLARK

that specifically infects and destroys this

bacterium. Cells with the gummy mucoid

coating, the researchers noted, were more

resistant to phage infection than regu-

lar cells were. What’s more, over gener-

ations, bacterial populations were more

likely to evolve the mucoid phenotypes in

the presence of Phi2 than they were in

its absence, indicating that the phenotype

may arise in Pseudomonas as an adaptive

response to phage attack.^2 Scanlan, now

at University College Cork (UCC) in Ire-

land, notes that more work is needed to

extend the findings to a clinical setting,

but the results hint that phages could in

some cases be responsible for driving bac-

teria to adopt more virulent phenotypes.

Such a role for viruses in driving bac-

terial evolution fits well with phages’

reputation as “the ultimate predators,”

says Colin Hill, a molecular microbiol-

ogist also at UCC who got his introduc-

tion to phages studying bacteria used in

making fermented foods such as cheese.

Hill notes an estimate commonly cited

in the context of marine biology—a field

that explored phage-bacteria interactions

long before human biology did—that

phages kill up to 50 percent of the bac-

teria in any environment every 48 hours.

“The thing that any bacterium has on its

mind most, if bacteria had minds, would

be phage,” Hill says, “because it’s the thing

most likely to kill them.”

Several in vivo animal studies lend

support to the idea that predatory phages

help shape bacterial evolution and com-

munity composition in the mamma-

lian microbiome. In 2019, for example,

researchers at Harvard Medical School

reported that phages not only directly

affect the bacteria they infect in the

mouse gut, but also influence the rest of

the microbiome community via cascad-

ing effects on the chemical and biologi-

cal composition of the gut.^3 Observa-

tional studies hint at similar processes

at work in the human gut. A few years

ago, researchers at Washington Univer-

sity Medical School in St. Louis observed

patterns of phage and bacterial popula-

tion dynamics that resembled predator-

prey cycles in the guts of children younger

than two years old: low bacterial densi-

ties at birth were followed by decreases

in phages, after which the bacteria would

rebound, and then the phages would fol-

low suit. The team concluded that these

cycles were likely a natural part of healthy

microbiome development.^4

Although researchers are only just

beginning to appreciate the importance of

phages in microbiome dynamics, they’ve

already begun to explore links to human

disease. Authors of one 2015 study reported

that Crohn’s disease and ulcerative coli-

tis patients showed elevated levels of cer-

tain phages, particularly within the viral

order Caudovirales. They proposed that an

altered virome could contribute to patho-

genesis through predator-prey interac-

tions between phages and their bacterial

hosts.^5 Other studies have explored possi-

ble phage-driven changes in the bacterial

community in human diseases such as dia-

PHAGE LIFECYCLE

Phages can interact with bacteria in two main ways. In the first, phages infect a bacterial

cell and hijack that cell’s protein-making machinery to replicate themselves, after which

the newly made virus particles lyse the bacterium and go on to infect more cells. In the

second process, known as lysogeny, the viral genome is incorporated into the bacterial

chromosome, becoming what’s known as a prophage, and lies dormant—potentially for

many generations—until certain biotic or abiotic factors in the bacterium or the environ-

ment induce it to excise itself from the chromosome and resume the cycle of viral replica-

tion, lysis, and infection of new cells.

Infection

DNA integration

Lysogeny

Production of phage Induction

components

Free virions

Lysis Prophage