Satellites, aerial photography, and computerized geographic imaging systems have enabled us to map the Earth with unprecedented accuracy. Planes now feature screens that let passengers monitor the flight’s path, while real-time websites map highway traffic flow with stunning precision. But when it comes to mapping another travel pattern—that of bacteria within the human body—scientists have only a vague idea of what is going on.
Now researchers at the U.K.‘s University of Cambridge are pioneering a new way to track the spread of bacteria within the body, integrating mathematical models with observational data to both predict and trace pathogenic movement.
Duncan Maskell and Pietro Mastroeni, both Cambridge immunologists, describe their work using Salmonella bacteria and mice in the October issue of the open access journal Public Library of Science Biology.
The researchers infected mice with fluorescent Salmonella and then studied their cells at specific time intervals to obtain “snapshots” of the infection process. What the scientists found was strikingly different from what previous experiments—done with tissue culture in Petri dishes rather than in live animals—had suggested.
“When mouse cells in a tissue culture are infected with bacteria, the bugs multiply and multiply until eventually the cell bursts,” Maskell said. But in the live mice, cells burst open, or lysed, regardless of how many bacteria were inside. Lysis, the researchers found, was not dependent upon the density of bacteria inside the cells but instead occurred randomly.
The researchers were also surprised to observe that at any given time, most mouse cells contained just a single bacterial cell, rather than many. Within a single cell, Mastroeni said, “we found that bacteria never grow to very high numbers.”
The fact that few cells contain many bacteria makes sense, Mastroeni said.
“When one cell carrying nine bacteria lyses, those bacteria will infect nine more cells, which will then each have one bacterium,” Mastroeni said. “There will always be many more cells with just one than with many.”
That means that a bacterium may spend most of its life jumping from host cell to host cell, rather than multiplying in one cozy spot, as was previously thought. If this is indeed true, then it could radically change the way doctors treat infectious diseases.
Instead of the blanket use of antibiotics, which can lead to drug resistance, therapies would specifically target bacteria within infected cells as well as those in transit between cells. “We will always need to have drugs that act intracellularly,” Maskell said, “but our results suggest that extracellular attack may be more valuable than we thought.”
Mastroeni and Maskell’s research focused on Salmonella but their results are applicable to a wide range of viral and bacterial microorganisms. And mapping microbes using “wet biology” combined with “dry mathematics” is a powerful approach that the Cambridge researchers believe could spawn an entirely new interdisciplinary practice.
“The mathematical modeling has allowed us to understand the data we acquired but also to predict some events,” said Mastroeni, “In order for the bacteria to spread from one cell to the other, they have to destroy the host, so the pattern, time, and mode of spread is very difficult observe dynamically. What the maps do is draw a model from which we can compare different possible [biological] scenarios with the mathematical data to see which one fits better. That it is the power of interaction of the math and the biology.”
