The good thing is it works on gram negatives which we really need new antibiotics for more than gram positives. I would be concerned how non-toxic it in humans as peptide antibiotics have historically been pretty nasty with lots of bad side effects.
Really the people doing the research have responsibility to speak out against this kind of jargon loading hype... Oh I see it is the title they chose for their own paper. I didn't read the paper, but the presence of hyping activities meant to appeal to the lowest common denominator has proven itself a decent heuristic so I won't bother.
Also, pretty much every bacteria is "multi-drug resistant".
These are peptides bound to a polymer particle that is not made out of peptides, but out of another polymer (PAMAM).
The vast majority of easily cultured bacteria have demonstrated the ability to acquire multi-drug resistance over time, but that doesn't mean that most bacteria that currently exist are multi-drug resistant.
I don't see how this is a correction of what I wrote. It is completely usual for a peptide to not only be a polymer itself, but also be attached to other polymers: https://en.wikipedia.org/wiki/Glycosylation
That term is totally meaningless in the title. Similarly, the term "multi-drug resistance" has always been about hyping up your paper. It was used until 2010 or so without any definition at all, look at all those papers:
This is definitely cool, but I don't see why bacteria wouldn't develop a resistance to this as well. I have a hard time getting excited about such things while the basic problem of reckless antibiotic use still exists.
I don't know that anyone says that they won't; I don't think anyone is saying "and we should just use this willy-nilly", but that it solves a particular problem we're dealing with now.
I totally agree though; there definitely needs to be reform with our use of antibiotics, because if we don't, we're going to be stuck with another gram-negative-esque problem.
They will develop resistance, but that is not a reason to not do it. I fully agree with you that reckless antibiotic use is the core problem, but public health solutions are slow and not sexy. It reminds me that Everyone wants a pill to treat for obesity--hundreds of millions of dollars have been spent chasing that dragon. in reality, lifestyle choices would be more effective, but habits like Big-Gulps and Couch-sitting die hard.
I hate to do this since someone on another thread recently admonished HN commenters as being like crabs that pull other crabs back down into the pot, but I think that this paper is largely PR fluff and worthy of criticism.
That being said, I am only going off of the abstract (If anyone has access to the paper, I'd love to read it) and I'd be happy to be proven wrong about any and all of what I say below.
ABSTRACT [w/ comments & opinions]
Here, we show that a class of antimicrobial agents, termed ‘structurally nanoengineered antimicrobial peptide polymers’ (SNAPPs) exhibit sub-μM activity
[if they had good MIC90 values (http://medical-dictionary.thefreedictionary.com/MIC90), they would have boasted about them. The fact that they don't discuss MIC90 values implies that they really haven't tested their compound against a large representative sample of Gram- pathogens. Either that, or they have done the work and the results aren't compelling.]
against all Gram-negative bacteria tested
[My suspicion is that "all" is a small number (see above). When I did this type of work, we routinely tested our compounds against about 200 random hospital isolates for a single species.]
including ESKAPE and colistin-resistant and MDR (CMDR) pathogens, while demonstrating low toxicity.
["low toxicity" is a weasel phrase]
SNAPPs are highly effective in combating CMDR Acinetobacter baumannii infections in vivo, the first example of a synthetic antimicrobial polymer with CMDR Gram-negative pathogen efficacy.
[This is noteworthy only from the standpoint that no one had previously been able to make synthetic polymers with this activity.]
Furthermore, we did not observe any resistance acquisition by A. baumannii (including the CMDR strain) to SNAPPs.
[This is a negative result with no measured boundary for resistance frequency. They don't say anything like: "We estimate that resistance to our SNAPPs is < 1e-11 per..." My suspicion is that they ran a quick experiment or two and didn't see any resistance, but they did not undertake a thorough analysis.]
Comprehensive analyses using a range of microscopy and (bio)assay techniques revealed that the antimicrobial activity of SNAPPs proceeds via a multimodal mechanism of bacterial cell death by outer membrane destabilization, unregulated ion movement across the cytoplasmic membrane and induction of the apoptotic-like death pathway,
[The authorts want to argue that it is more difficult for microbes to acquire resistance to SNAPPs because the SNAPPs have multiple purported mechanism(s) of action (OM destabilization, ion gradient destabilization, etc.). If you kill the microbe 3 different ways, then it will be difficult for the microbe to evolve resistance against you.
There are several problems with this conclusion. First, their assays do not pinpoint the MOA of their compound. It is possible that their compound "hits" a _single_ target that has multiple effects on membrane stability in Gram-negatives. If this is correct, then resistance might be trivial.
Alternatively, if they are correct, and the SNAPPs have multiple, independent destabilizing effects on the microbial membranes, I would be concerned that the SNAPPs would be indiscriminate enough to have an increased likelihood of being toxic to all membranes (human included). This is speculation on my part, however.
Finally, there is no mention of the efficacy of the SNAPPs against Gram- that contain multi-drug resistant efflux transporters (https://en.wikipedia.org/wiki/Efflux_(microbiology)). I would be interested to know how effective SNAPPs are against these pathogens.]
possibly accounting for why we did not observe resistance to SNAPPs in...
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Here is the link to the abstract [1].
1. http://www.nature.com/articles/nmicrobiol2016162
>"peptides fall under the broad chemical classes of biological oligomers and polymers" https://en.wikipedia.org/wiki/Peptide
Really the people doing the research have responsibility to speak out against this kind of jargon loading hype... Oh I see it is the title they chose for their own paper. I didn't read the paper, but the presence of hyping activities meant to appeal to the lowest common denominator has proven itself a decent heuristic so I won't bother.
Also, pretty much every bacteria is "multi-drug resistant".
The vast majority of easily cultured bacteria have demonstrated the ability to acquire multi-drug resistance over time, but that doesn't mean that most bacteria that currently exist are multi-drug resistant.
That term is totally meaningless in the title. Similarly, the term "multi-drug resistance" has always been about hyping up your paper. It was used until 2010 or so without any definition at all, look at all those papers:
https://www.ncbi.nlm.nih.gov/pubmed/?term=multi+drug+resista...
I totally agree though; there definitely needs to be reform with our use of antibiotics, because if we don't, we're going to be stuck with another gram-negative-esque problem.
Clearly. I take aspirin when I have a cold, so I have no qualms bout treating symptoms.
I just have trouble seeing this as a meaningful step in solving the problem at hand.
That being said, I am only going off of the abstract (If anyone has access to the paper, I'd love to read it) and I'd be happy to be proven wrong about any and all of what I say below.
ABSTRACT [w/ comments & opinions] Here, we show that a class of antimicrobial agents, termed ‘structurally nanoengineered antimicrobial peptide polymers’ (SNAPPs) exhibit sub-μM activity [if they had good MIC90 values (http://medical-dictionary.thefreedictionary.com/MIC90), they would have boasted about them. The fact that they don't discuss MIC90 values implies that they really haven't tested their compound against a large representative sample of Gram- pathogens. Either that, or they have done the work and the results aren't compelling.]
against all Gram-negative bacteria tested [My suspicion is that "all" is a small number (see above). When I did this type of work, we routinely tested our compounds against about 200 random hospital isolates for a single species.]
including ESKAPE and colistin-resistant and MDR (CMDR) pathogens, while demonstrating low toxicity. ["low toxicity" is a weasel phrase]
SNAPPs are highly effective in combating CMDR Acinetobacter baumannii infections in vivo, the first example of a synthetic antimicrobial polymer with CMDR Gram-negative pathogen efficacy. [This is noteworthy only from the standpoint that no one had previously been able to make synthetic polymers with this activity.]
Furthermore, we did not observe any resistance acquisition by A. baumannii (including the CMDR strain) to SNAPPs. [This is a negative result with no measured boundary for resistance frequency. They don't say anything like: "We estimate that resistance to our SNAPPs is < 1e-11 per..." My suspicion is that they ran a quick experiment or two and didn't see any resistance, but they did not undertake a thorough analysis.]
Comprehensive analyses using a range of microscopy and (bio)assay techniques revealed that the antimicrobial activity of SNAPPs proceeds via a multimodal mechanism of bacterial cell death by outer membrane destabilization, unregulated ion movement across the cytoplasmic membrane and induction of the apoptotic-like death pathway, [The authorts want to argue that it is more difficult for microbes to acquire resistance to SNAPPs because the SNAPPs have multiple purported mechanism(s) of action (OM destabilization, ion gradient destabilization, etc.). If you kill the microbe 3 different ways, then it will be difficult for the microbe to evolve resistance against you.
There are several problems with this conclusion. First, their assays do not pinpoint the MOA of their compound. It is possible that their compound "hits" a _single_ target that has multiple effects on membrane stability in Gram-negatives. If this is correct, then resistance might be trivial.
Alternatively, if they are correct, and the SNAPPs have multiple, independent destabilizing effects on the microbial membranes, I would be concerned that the SNAPPs would be indiscriminate enough to have an increased likelihood of being toxic to all membranes (human included). This is speculation on my part, however.
Finally, there is no mention of the efficacy of the SNAPPs against Gram- that contain multi-drug resistant efflux transporters (https://en.wikipedia.org/wiki/Efflux_(microbiology)). I would be interested to know how effective SNAPPs are against these pathogens.]
possibly accounting for why we did not observe resistance to SNAPPs in...