Testing and Expanding Models: The Example of Antibiotic Resistance

Antibiotic resistance has become a major medical problem.
A major report on the seriousness of the problem was in the news this morning (May 11, 2014).
[It is] a problem so serious that it threatens the achievements of modern medicine…. A post-antibiotic era, in which common infections and minor injuries can kill, far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century. ( http://www.nytimes.com/2014/05/11/opinion/sunday/the-rise-of-antibiotic-resistance.html?hp&rref=opinion)

This blog provides an example of the importance of model building in science. Models are developed to help understand natural phenomena. When the model is constructed, it becomes a way to reveal new questions about the phenomena.
The conventional model for antibiotic resistance
The antibiotic action against the pathogen can be seen as an environmental pressure. Those pathogens within the population that possess a mutation that allows them to survive live to reproduce and will then pass this trait to their offspring, which leads to the evolution of a fully resistant colony of the pathogen.

Does the model account for all of the possibilities?
Is antibiotic resistance the result of using antibiotics to treat bacterial infections?
What if we able to go back in time to the time before the advent of penicillin (the first antibiotic) and test modern antibiotics on bacteria that have not experienced them?
In 2010 microbiologist Dr. Gerry Wright identified way to investigate the question when he discovered that the Lechugilla cave complex in New Mexico could serve as a kind of time machine because the 1,600 foot deep cave walls were covered with bacteria that had not been exposed to antibiotics over the four million year history of caves. (“http://www.nytimes.com/2014/05/08/science/antibiotic-resistant-germs-lying-in-wait.html)
Dr. Wright’s team found that there were many bacteria in the cave that were resistant to the rich cocktail of antibiotics used by the team. Further, it was found that the pre-antibiotic bacteria possessed many of genes that have evolved in the modern anti-resistant bacteria.
Using DNA databases filled with bacterial DNA from all over the world, those genes that made antibiotic resistance possible were ubiquitous.
Such investigations have uncovered additional mechanisms by which bacteria can become resistant. It is known that bacteria can borrow DNA from other bacteria. It was by this mechanism called “horizontal gene transfer” that a powerful antibiotic called vancomycin began acquiring resistance in the 1980s. It turns out that the resistance was acquired when the DNA of the bacterium that was the source of vancomycin was shared by way of horizontal gene transfer with certain disease causing bacteria.
This example illustrates that model building is a dynamic process in which the development of a model helps investigators to identify new questions that allow for the model to be both tested and expanded.
The idea for this blog came from Carl Zimmer’s May 8, 2014, “Matter” column (http://www.nytimes.com/2014/05/08/science/antibiotic-resistant-germs-lying-in-wait.html). It’s application to model building is mine.
You might be interested in looking for the following article in Nature.

D’Costa, Vanessa; King, Christine; Kalan, Lindsay; Morar, Mariya; Sung, Wilson; Schwarz, Carsten; Froese, Duane; Zazula, Grant; Calmels, Fabrice; Debruyne, Regis; Golding, G. Brian; Poinar, Hendrik N.; Wright, Gerard D. (September 2011). “Antibiotic resistance is ancient”. Nature 477 (7365): 457–461. Bibcode:2011Natur.477..457D. doi:10.1038/nature10388. PMID 21881561.


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