Within-host evolution of Achromobacter xylosoxidans

Abstract

Patients with Cystic Fibrosis develop chronic infection in the lungs. Achromobacter xylosoxidans is an opportunistic pathogen that is frequently found in the lungs of the patients. In the present study, phylogenetic analysis on whole genome sequences from patients with A. xylosoxidans was performed and libraries were prepared with information on genetic variation both in the entire genome and in coding regions to characterize and enable prediction of within-host evolution. The results suggest co-existence of related strains with specific niches, including hypermutators. This supports the idea that genomic analyses could contribute to the future treatments of chronic infection in CF patients by directing treatment regiments and/or guiding the pathogenic populations into more benevolent evolutionary trajectories.

Popular Abstract

Predicting a pathogen

New insights into the DNA of disease-causing organisms give researchers the opportunity to predict their evolution and opens for novel treatments that stop pathogens in their tracks.

For 160 years now, our current evolutionary paradigm has been a framework for life science theory. Even though the basic idea is so simple it can be formulated with just a few words “evolution is change over time” it relies on complex enough assumptions that it is frequently misinterpreted. Take for example the 2011 film “X-men first class” which features a mutant aptly named “Darwin” that has the power of “reactive mutation”. If the character e.g. gets punched hard, he produces thick, rocklike skin in seconds. Even if we disregard the other misconceptions in this comic book world, this is hilarious. We can rephrase the definition of evolution to “a change in genetic information across generations” to highlight these assumptions, that are well known, but still somehow, at times, forgotten. The mutant called Darwin is part of one generation, as a multicellular organism he is composed of many cells containing their own genetic information. There are several reasons genetic information might change on a large scale in one person, one being radiation interfering with DNA. A virus may insert its own genetic information in several cells. However, the mutations will be random and the absolute majority of acquired mutations would likely be either unnoticeable or harmful for the individual that acquires them.

One important thing to note about evolution is that it is without intent. Evolution is not some kind of force that strives to improve all organisms, rather it is the cruel scythe of Father Time, sending individuals and species into oblivion when they lack the necessary mutations that allow them to adapt to their environment by chance. Therefore, if we look at the history of evolution of species, the absolute majority have already gone extinct. In fact, the evolutionary process is so random and bereft of intent that it has been likened to a very inebriated person walking along a well-trafficked railroad. If the mutant Darwin existed, he would likely have died of cancer as soon as his power manifested. I would assume no-one bases their understanding of evolution on comic books or films, but we sometimes see variations of these misconceptions in everyday discussions of disease-causing organisms and hot topics of the day such as antibiotic resistance and COVID-19. Much of this uncertainty in the common understanding of evolution likely stems from the amazing fact that even if all the above is true, we can analyze and make predictions about evolution, this is the power of genetics. Back in the days of Mendel and for almost a century after, geneticists had to rely on traits that were easily observed and measured such as the color of a flower. This was powerful enough to aid in breeding types of organisms with traits that were considered attractive, but also often associated with unforeseen effects. By the end of the 20th century, genetics entered a new era. DNA could be decoded quickly and cheaply enough to enable researchers to create libraries of genetic information found in species. Now instead of looking at one or a few easily observable traits in an organism, variations in the genetic sequence can be observed, revealing mutations and variants of all the genetic information found in the organism.

At the Biomedical Centre in Lund, a group has collected samples from patients with the genetic illness Cystic Fibrosis. Patients with Cystic Fibrosis have a mutation that affects the ability of their cells to transport ions across cell membranes. This is a particularly important function in the entire body, and it causes several effects, e.g. the sweat of a person with Cystic Fibrosis tastes saltier than that of a person with normal ion transport. One important effect of the illness is that it changes the composition of mucus in the lungs, the change opens for bacteria that would otherwise be harmless to colonize the lungs and respiratory tract. Further, over time, the community of microflora in the lungs changes as the disease progresses. Modern treatments have enabled people with Cystic Fibrosis to survive well into adulthood, but life expectancy is still shorter than the average and much time is spent every day on treating the condition.

The samples were collected over a time of 8 years from seven patients with Cystic Fibrosis and contain bacteria that the group is interested in. It has been shown that the presence of some bacteria in patients lungs is associated with a more benign disease progression while it is also true that it is very hard to treat infection that worsen the condition using conventional means; antibiotics. When bacteria adapt to a human host, the human effectively becomes its environment and conditions within that human select for certain traits in the bacteria. Treating these infections is like playing a game of chess, where every move is either an adaptation by the bacteria to the host environment or a response by the host immune system and medical interventions and, just like in chess, reacting to your opponent’s immediate move is not enough to win the game, you have to be able to predict their future moves, their strategy, and devise your own to beat it. To improve this prediction, this group is one of several that culture bacteria found in samples from patients, extract the DNA of the infectious bacteria and analyze it to reveal patterns of evolution over time in patients. In the first stage of the analysis, patterns of loss or gain of genes or groups of genes have indicated that there is significant adaptation in certain genes that control important functions such as bacterial metabolism, antibiotic resistance and the ability to mutate very quickly. The last trait is what is known as a “hypermutator”, the bacteria sacrifice some of the mechanisms that protect against harmful mutations to rapidly produce cells that have vital mutations in a harsh environment. This could be, for example, antibiotics resistance and the information could one day be used to improve treatment both generally for chronic infection in Cystic Fibrosis and to tailor treatments to individuals based on their present lung microflora. The group is now moving into the next phase, where the function of the genes that have been discovered to be important in adapting to the host environment are to be confirmed.

• author: Knulst, Mattis
• supervisor: Magnus Paulsson
• organization: Degree Projects in Biology
• course: BIOY01 20192
• year: 2020
• type: M2 - Bachelor Degree
• subject: Biology and Life Sciences
• language: English
• id: 9023420
• date added to LUP: 2020-06-30 09:28:53
• date last changed: 2020-06-30 09:28:53