Combating multidrug-resistant bacteria with nanoengineered peptide polymers

Here is the link to the abstract [1].

1. http://www.nature.com/articles/nmicrobiol2016162

Media stories http://www.sciencealert.com/the-science-world-s-freaking-out... http://www.telegraph.co.uk/women/health/does-this-25-year-ol...

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 CMDR bacteria. [Again, I think they're speculating wildly based on a few negative results.]

To me, this is a standard story that you occasionally see from academic chemistry labs. They have an interesting compound and/or technology. They see some antimicrobial activity with their compound and they collaborate with a microbiology lab to demonstrate some level of efficacy.

Here, the microbiology lab is one that has been historically devoted to oral microbiology (http://findanexpert.unimelb.edu.au/display/person12757#tab-p...). My point is that neither the chemistry lab nor the oral micro lab are really equipped to know the ins and outs of antibiotic drug development. They are simply making a splash with the terms multi-drug-resistance and nanoengineered.

>"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".