Uh, so looking back over the paper I discussed in the last report, I now realize that there are a couple more things of importance to discuss from that paper. In my defense though, explaining why the data suggested that antibiotics interfered with phage replication took longer than I expected; the text wall was high enough as it was without another topic added into the mix. So while I’m tempted to move immediately to a new, potentially more exciting paper, I feel obligated to address these things before finishing up with “Synergy and Order Effects of Antibiotics and Phages” for good.
Phage control of antibiotic resistant bacteria
Yeah, I mean this is kind of the main potential application of bacteriophages, killing antibiotic-resistant bacteria, so I definitely need to talk about this. Phages work against antibiotic-resistant bacteria, which is good news. The data says as much, look at this figure here.
The red and blue bars may seem a little disorienting at first, but as you can see, the blue bar is for the total number of cells present, and the red bar is for the cells out of that total that are resistant to the antibiotic used.
The x axis labels may seem a little confusing as well, but what you just need to focus on is the bit to the left of the hyphen, which designates what the bacteria were treated with. Con for control or nothing, Cip/Gen for the antibiotics, and NCip/NGen for the phages and antibiotics.
Most importantly, note how the antibiotic-only treatment bacterial populations are pretty much the same size as the control population where no treatment was applied. In contrast, the combined treatment groups have much lower population sizes. So it seems phages can be applied to manage antibiotic-resistant bacterial populations. Great!
Synergy
Synergy is thankfully not too hard of a concept to explain. You know the phrase “greater than the sum of its parts”? That’s pretty much what synergy is about, but in the context of treatments’ ability to kill bacteria and not, I don’t know, sandwiches.
WAIT. THAT REMINDS ME. RULE OF SANDWICH
***tangent begins***
Don’t bother Googling “rule of sandwich.” It’s something that I thought of a couple of months ago. I thought it was pretty clever, like something Randall Munroe of xkcd webcomic would talk about. The rule is that all sandwiches must be tastier than the sum of their parts, otherwise they would not be worth the energy expenditure to work against entropy and form a more ordered product from disordered reactants. The reaction of sandwich-genesis is not spontaneous, unfortunately.
***tangent ends***
Yeah, so synergy just means that the combined usage of Treatment A and Treatment B kills more bacteria somehow than would be expected based off of the peformance of Treatment A and B, separately. As a simple example, say Treatment A kills 3 bacteria and B kills 4. If there were a synergy effect in play between Treatment A and B, the combined treatment would kill more than 7 bacteria. So that’s what synergy is.
Coming back to the context of the paper, what’s interesting is that synergy was exhibited in a couple of places: firstly, between the two different types of phages used in the experiment and secondly, between combined phages and antibiotics. To be more specific, by “antibiotics,” I mean 1X and 8x concentrations of ceftazidime, and a 1x concentration of ciprofloxacin. Stated fully, the two phages, and the two phages with these antibiotics killed more bacteria together than expected based on their individual performance.
If you look again at one of the figures that we examined in the first research report, you can sort of eyeball the bars and see how the data supports this.
I’m working under the assumption that the difference in height between the control bar (the black one labeled as Con) and the bars for treatment population indicates how much bacteria that treatment was able to kill (remember that the y axis represents the number of bacteria present basically).
Think about it this way: the only difference between the control population and the treatment population of interest is the presence of the treatment, so it must responsible for the difference in bacterial population, right? So by comparing the difference in height between the control and experimental treatment group, one should be able to tell how effective it was.
Here’s the annotated figure, hopefully, you can see how the data suggests synergy occurs.
As you can see for the phages (NP1 and NP3 are the two phages, N is for both) ΔA/NP1 and ΔB/NP3 added together is less than ΔC, the difference for the N/combined phage group. Synergy!
Put in terms of bacteria-killing, the amount of bacteria killed by NP1 and NP3 when they are by themselves, added up, is less than the amount of bacteria killed when both phages are present at the same time. Is it magic? It’s synergy. Maybe the same thing. Sort of seems like it to me. The phages complement each other in some way that hasn’t been really thoroughly explored to the best of my limited knowledge.
The same goes for N, Cef1, N-Cef1 and N, Cip1, and N-Cip1 treatment groups: the data suggests synergy. I didn’t annotate the figures for that, but I hope you have a picture in your head now when I say that synergy exists between two treatments.
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So yep, that’s the important/interesting bits that can be gleaned from this paper. There are a couple morals of the story to be had here: firstly, the interactions between phages and antibiotics are not all bad, in fact, it appears the positive, synergistic interactions are far more common.
Secondly, due to these mostly complementary relationships between phages and antibiotics, it appears that while phages are a viable solution for antibiotic-resistant bacteria, I’d speculate that phages in the future are not going to work in isolation, but alongside antibiotics to provide the best treatment possible.
Thanks for reading!
- BJW
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