new paper

[Guest guest]

This is related to stuff I've posted on before, from the same authors.

" Furthermore, we document that the 2-aminoimidazole/triazole conjugate will also

re-sensitize multi-drug resistant strains of bacteria to the effects of

conventional antibiotics, including MRSA and multi-drug resistant Acinetobacter

baumannii. "

I have no idea what this means concretely, having not read the paper.

-

==================

Antimicrob Agents Chemother. 2010 Mar 8. [Epub ahead of print]

Synergistic Effects Between Conventional Antibiotics and

2-Aminoimidazole-Derived Antibiofilm Agents.

SA, Huigens RW 3rd, Cavanagh J, Melander C.

Department of Chemistry, North Carolina State University, Raleigh, NC, 27695;

Department of Molecular and Structural Biochemistry, North Carolina State

University, Raleigh, NC 27695.

2-Aminoimidazoles are an emerging class of small molecules that possess the

ability to inhibit and disperse biofilms across bacterial order, class and

phylum. Herein, we report the synergistic effect between a

2-aminoimidazole/triazole conjugate and antibiotics toward dispersing

pre-established biofilms, cumulating with a three orders of magnitude increase

of biofilm dispersion towards Staphylococcus aureus biofilms. Furthermore, we

document that the 2-aminoimidazole/triazole conjugate will also re-sensitize

multi-drug resistant strains of bacteria to the effects of conventional

antibiotics, including MRSA and multi-drug resistant Acinetobacter baumannii.

PMID: 20211901 [PubMed - as supplied by publisher]

[Guest guest]

I did a listless skim of the paper.

1. It doesn't say what the resistance mechanisms of the multi-drug resistant

bacteria they tested are, unfortunately (I could look it up, but probably never

will). Some of those mechanisms can be expressed conditionally, for example

efflux pumps that expel a antibiotic molecule, or enzymes that destroy it. There

is reason to think that their new molecule blocks communication. So it could be

that the likes of MRSA only express their resistance mechanisms while

communicating with each other properly. That is, without communication they

simply don't manufacture the degradatory enzyme of efflux pump in question. The

purpose of communication might be, perhaps, to learn that the other cells (not

just the cell in question) are in a state of physiological distress, which would

mean there is a chemical threat afoot, rather than the cell in question having

simply been eaten by an amoeba or something, in which case it should take other,

different measures.

On the other hand, some antibiotic resistance mechanisms are unalterable, eg

mutations that change the ribosome site that tetracycline binds to. These cannot

be turned on and off so it is hard to see how this new molecule could do so in

any way. But maybe the bacteria they tested didn't have any resistance

mechanisms of this type.

2. The new molecule didn't work in certain ionic environments. I have no idea if

the human body presents such ionic conditions or not. But I assume they do. They

didn't seem disheartened by it. Instead they claimed they were continuing to

attempt to develop it towards medical use. It did OK on a hemolysis test -- ie,

it doesnt melt red cells at the applicable concentration. But that is the first

of a zillion toxicology tests. And there are many other tough hurdles (many

candidate drugs don't absorb well, or aren't at all stable in the human body,

etc).

[Guest guest]

sounds technical. What concerns me is that most biofilm research seems to be targeted at implants, artificial hips, steel pins etc. Bio-films really like to attach themselves to these smooth surfaces, which can cause orthopedic surgeries to fail and end up wasting a whole buncha money, so of course surgeons and insurance companies are interested in finding ways to curtail biofilms in those appllications.

But unless things have changed dramatically, I don't think they care a whole lot about individuals with chronic infections (that's why limb amputation is so popular, it's cheap). Sinus surgeons would lose considerable income if they were to find a way to prevent bugs from adhering to sinus walls, so I doubt there's much push for progress from those camps. Someday, somebody will figure it out...would be nice if they could figure it out while we're still here. :-)

From: hodolog1ca <usenethod@...>Subject: [infections] Re: new paperinfections Date: Wednesday, March 17, 2010, 5:49 PM

I did a listless skim of the paper. 1. It doesn't say what the resistance mechanisms of the multi-drug resistant bacteria they tested are, unfortunately (I could look it up, but probably never will). Some of those mechanisms can be expressed conditionally, for example efflux pumps that expel a antibiotic molecule, or enzymes that destroy it. There is reason to think that their new molecule blocks communication. So it could be that the likes of MRSA only express their resistance mechanisms while communicating with each other properly. That is, without communication they simply don't manufacture the degradatory enzyme of efflux pump in question. The purpose of communication might be, perhaps, to learn that the other cells (not just the cell in question) are in a state of physiological distress, which would mean there is a chemical threat afoot, rather than the cell in question having simply been eaten by an amoeba or something, in

which case it should take other, different measures.On the other hand, some antibiotic resistance mechanisms are unalterable, eg mutations that change the ribosome site that tetracycline binds to. These cannot be turned on and off so it is hard to see how this new molecule could do so in any way. But maybe the bacteria they tested didn't have any resistance mechanisms of this type.2. The new molecule didn't work in certain ionic environments. I have no idea if the human body presents such ionic conditions or not. But I assume they do. They didn't seem disheartened by it. Instead they claimed they were continuing to attempt to develop it towards medical use. It did OK on a hemolysis test -- ie, it doesnt melt red cells at the applicable concentration. But that is the first of a zillion toxicology tests. And there are many other tough hurdles (many candidate drugs don't absorb well, or aren't at all stable in the human body,

etc).

[Guest guest]

Maybe it's simpler than that- maybe they're talking about a variant form

reverting back to it's suscetible form.

Interesting though.

Barb

--- In infections , " hodolog1ca " <usenethod@...>

wrote:

>

>

>

> I did a listless skim of the paper.

>

> 1. It doesn't say what the resistance mechanisms of the multi-drug resistant

bacteria they tested are, unfortunately (I could look it up, but probably never

will). Some of those mechanisms can be expressed conditionally, for example

efflux pumps that expel a antibiotic molecule, or enzymes that destroy it. There

is reason to think that their new molecule blocks communication. So it could be

that the likes of MRSA only express their resistance mechanisms while

communicating with each other properly. That is, without communication they

simply don't manufacture the degradatory enzyme of efflux pump in question. The

purpose of communication might be, perhaps, to learn that the other cells (not

just the cell in question) are in a state of physiological distress, which would

mean there is a chemical threat afoot, rather than the cell in question having

simply been eaten by an amoeba or something, in which case it should take other,

different measures.

>

> On the other hand, some antibiotic resistance mechanisms are unalterable, eg

mutations that change the ribosome site that tetracycline binds to. These cannot

be turned on and off so it is hard to see how this new molecule could do so in

any way. But maybe the bacteria they tested didn't have any resistance

mechanisms of this type.

>

>

> 2. The new molecule didn't work in certain ionic environments. I have no idea

if the human body presents such ionic conditions or not. But I assume they do.

They didn't seem disheartened by it. Instead they claimed they were continuing

to attempt to develop it towards medical use. It did OK on a hemolysis test --

ie, it doesnt melt red cells at the applicable concentration. But that is the

first of a zillion toxicology tests. And there are many other tough hurdles

(many candidate drugs don't absorb well, or aren't at all stable in the human

body, etc).

>

[Guest guest]

Maybe, but probably not. Variants such as Borrelia cysts, and their reversion to

normal forms, are as far as we know a matter of phenotypic changes -- that is,

changes in an organism's physiology that don't involve a change in the genome.

Almost any change in a human individual, for example -- except for cancer -- are

phenotypic. But most or all of the changes that make Staph aureus into

multi-drug-resistant Staph aureus, are genomic changes. MRSA (Staph aureus that

is resistant to methycillin, plus many other drugs as well) is something that is

changed genomically. It isn't just a physiological variant.

> Maybe it's simpler than that- maybe they're talking about a variant form

reverting back to it's suscetible form.

>

> Interesting though.

> Barb