As living organisms, bacteria are encoded by DNA, and DNA occasionally mutates. Sometimes genetic mutations render a bacterium immune to an antibiotic’s chemical tactics. The few cells that might escape antibiotic pressure then have a sudden advantage: with their counterparts wiped out, resources abound, and the remaining antibiotic-resistant bacteria proliferate. It’s a problem not only for the host—you or me when we are treated with an antibiotic and develop a resistant strain—but also for anyone with whom we happen to share our resistant bacteria, say, on a door handle or keyboard. In fact, most resistant bacteria develop not in people but in livestock fed antibiotics to promote growth; these resistant bacteria infect people through contaminated animal products. This is how even antibiotic “naive” people come to be infected with resistant strains of bacteria.
I see this all the time as a family doctor. A woman has a urinary tract infection. I tell her that her bacteria are resistant to this or that antibiotic, and she says, “But I’ve never taken any of those.” Welcome to the global human soup.
You can’t cheat evolution.
People often cite evolution for antibiotic resistance, but that’s not the case.
There’s an inverse relation between bacteriophage resistance and antibiotic resistance. Antibiotic resistance requires more efflux pumps and less strong cell walls, and bacteriophage resistance requires stronger cell walls and less efflux pumps.
What’s happening is allele drift within colonies towards better antibiotic resistance, but these colonies are also very susceptible to bacteriophages.
This is no different than the frequency of spots on deer in a population group increasing our decreasing over generations.
I know many people call that evolution, but I think it’s important to be precise with our definitions. These traits for antibiotic or bacteriophage resistance are already present within the genome. They each just get expressed under different conditions, and the phenotypic strength of each is inversely proportional to the expression of the other.
This isn’t a simple or straightforward relationship. Genetics are always incredibly complex, but this relationship is confirmed.
I understand what you’re saying about drift, but I’m not sure that feels sufficient to explain the prevalence of anti-biotic resistance. You’re right to highlight that the genes for antibiotic resistance already exist and it’s just a question of how prevalent they are in different populations/generations, but I don’t think this excludes it from being evolution. I would consider the human use of antibiotics in medicine and agriculture to be a selective pressure that is increasing the prevalence of antibiotic resistant genes in bacteria, especially in combination with human activities that facilitate the global spread of antimicrobial resistance.
I agree that “evolution” is a pretty muddy term though, which is made trickier by the fact that with how language evolves, some people use it in a different sense than what is probably strictly “correct”. I’m a biochemist, for example, and I don’t know if I could give a strictly correct definition for evolution. Along those lines, I realise I may be misinterpreting your point.
Separate to all that, it sounds like you’re well versed on the bacteriophage stuff, are there any articles that you think cover the topic well? I’m more of a protein structure gal myself, so I only have patchy, undergrad level knowledge of microbiology stuff.
A succinct definition of evolution is “The change of allele frequencies over time.” Even “allelic drift” is evolution.
For bacteria, population sizes are big enough that simple variants like base substitutions can occur at every single base in the genome over a short period of time. Some of these are important to the development and redevelopment of resistances. Once one allele has spread enough, compensatory mutations can bring about combinations that weren’t seen before.
Antibiotic resistance is definitely an evolved trait, and it’s the reason why multi-resistance and resistance to brand new antibiotics is becoming such a problem.
One interesting discovery was the remains of a person in Peru from something like 900 years ago. One really interesting aspect of the discovery was the gut bacteria in the remains. When they sequenced the genome of some of the bacteria they found that they were the same species as we have today. But more importantly was that the genes that encode for antibiotic resistance existed in those bacteria.
https://www.ancient-origins.net/news-history-archaeology/ancient-peruvian-mummy-surprises-researchers-antibiotic-resistant-genes-020581
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589460/
The discussion here isn’t about how antibiotic resistance first came about, the discussion is about how bacteria have been reacting to modern medicine. Why are bacteria becoming harder to treat with antibiotics as time goes on?
The point I was making is that bacteria already have antibiotic resistance in the genome, but the phenotypic expression is inversely related to bacteriophage resistance.
Antibiotic resistance needs
weaker/more flexible cell walls
more efflux pumps
Bacteriophage resistance needs
In any population group there’s going to be variation in the expression of genes (the phenotype). In that population there are going to be individuals with greater antibiotic resistance and others with greater bacteriophage resistance. When antibiotics are introduced it kills most of the bacteria, but there can be a few individuals with higher antibiotic resistance that can potentially repopulate a new generation with an allele frequency shifted towards higher antibiotic resistance.
I know what I just described is “natural selection”, but that’s not evolution. Natural selection is one of the processes that is part of evolution, but it is not evolution in of itself.
Edit: formatting
Your comment is confusing. Yes, genetic drift is evolution, so saying “people cite evolution” and then dismissing it is not a good approach.
Perhaps you mean it isn’t natural selection, but then the trait being under balancing selection (a tradeoff between phage resistance and antibiotic resistance) is still under selection. And the presence of antibiotics shifts the balance heavily in favor of resistance even if that means decreasing resilience in the absence of antibiotics.
You say the traits are already there and just need to be expressed, so perhaps it’s mutation you think is not happening. That’s often the case, but it still took mutation to create the means of resistance to begin with. Some of it is passed around on plasmids, but they the traits had to evolve in the first place. In addition, once resistance becomes dominant, there is enough diversity to select for compensatory mutations that increase the fitness of the resistant bacteria. Things like compensating for cell wall weaknesses or pumps that were initially favored despite their drawbacks.
Not “genetic drift”. Although I did forget a critical word. I meant to say “allele frequency drift” which is distinctly different than genetic drift.
Allele frequency drift simply describes a shift in how common a genetic trait exists, or is expressed, within a population group. The overall genetics of the group are the same. Even if there were no changes to the collective genetics of a population over millions of years (no evolution) you can still have allele frequency drift.
This is what I mean by “allele frequency drift isn’t evolution”. It’s a mathematical expression of the ratio a gene is expressed within a population group. It doesn’t describe any genomic changes or mutations.
The first generation can have frequency 1.0 of a trait, gen 2 can have 1.5, gen 3 can have 2.0, and then back down again over the next few generations. But generation 10 can have an (nearly) identical genome to generation 1.
You are reporting one side of a three-sided coin. You can find instances of phage resistance linked to increased antibiotic susceptibility, decreased antibiotic susceptibility, and in most cases no change in antibiotic susceptibility. Studies linking phage resistance to increased antibiotic susceptibility are based on in vitro selections resulting in genetic disruptions that would never arise in a host, and are likely due to the relaxation of selective pressures when bacteria are grown in rich broth. For example, phage that use LPS as a receptor cannot infect cells with LPS defects, but those cells are so sick and mucoid that they become susceptible to just about any other stress, including antibiotics. We never isolate bacteria with LPS defects in the wild because they would go extinct in any competitive environment.
The real lessons we need to learn from phages and other antibacterial systems is that resistance is inevitable. These systems have built in flexibility and modularity to accommodate changes and mutate rapidly. Almost all of these systems follow a similar pattern: bind to target cell, get inside target cell, destroy target cell. There are many ways to accomplish each of those steps, and these systems are set up to rapidly evolve new ways accomplish each. This evolution is not limited to the slow single mutations we often associate with evolution. We often observe recombination where another target cell binding domain can be swapped in to generate a new functional system.
Modern phage therapy advocates suggest combination therapies, where multiple antibacterial agents are deployed to substantially lower the rate of resistance. But we will never get that number to zero. Also phage therapy is limited in efficacy based on the site of infection (phage do not penetrate tissues like small molecule antibiotics do) Instead of evolution being a brick wall for therapy, we need to play the game. We need to get off of broad-spectrum antibiotics, focus on functional modules (like cell entry, cell toxicity, etc), and reform our regulatory structure to enable mixing and matching of these modules in regimented phases in response to the resistance that we know will arise. Phage therapy is not the answer; the phage evolutionary cycle is the answer.