multidrug efflux in natural confrontations

[Guest guest]

Ive been reading Kim .

It seems at least one plant produces chemicals that block bacterial

multidrug efflux pumps, thus allowing otherwise-weak plant

antimicrobials to prevent infection effectively.

Conceivably, unless I'm overlooking something, animals might also

contain antimicrobial small molecules (I dont think any are known).

Bacteria, via sensor proteins, can upregulate efflux pumps in the

event of toxic insult (tho not fast enough to rescue themselves from

abx in vitro). Substances of living animals - amphipathic peptides

or undiscovered small molecules - might induce the gross

upregulation of efflux in bacterial pathogens (only some - why?) in

some way that would not occur in vitro. The bacteria would then

enjoy significant resistance to all medicinal antibacterials, such

as we evidently observe.

This begs the question why animals dont produce inhibitors of mutli-

drug effluxers. However, at present it seems only one plant is

confirmed to do so.

http://www.pubmedcentral.gov/articlerender.fcgi?

tool=pubmed & pubmedid=12234835

" A vast majority of small-molecule plant antimicrobials are agents

with weak or narrow-spectrum activities, while bacteria, yeast, and

fungi produce antibiotics that both are often effective and have

broad spectra of activity. The nature of this disparity is puzzling.

[...]

" Our recent work with berberine, a cationic alkaloid, offered a

possible explanation for the apparent ineffectiveness of plant

antimicrobials (45, 46). Berberine is a weak antimicrobial produced

by a wide variety of plant species. It is an amphipathic cation that

resembles quaternary ammonium antiseptics in its chemical properties

and possibly in its mechanism of action as well. The likely targets

of berberine are the cytoplasmic membrane and DNA, into which it

intercalates (20). Amphipathic cations are the preferred substrates

of most MDRs (26), and we reasoned that the low level of activity of

berberine might result from effective efflux. We found this to be

true with a model bacterial pathogen, S. aureus: both disruption of

the main MDR (NorA) and application of an MDR inhibitor strongly

potentiated the antimicrobial action of berberine (18). Next, we

wondered whether plants producing berberine have also evolved an MDR

inhibitor to disable the resistance mechanism of bacteria. We found

that Berberis plants produce 5Œ-MHC-D, which completely blocked NorA

and acted in synergy with berberine (45, 46). In the absence of

efflux, berberine, a hydrophobic cation, accumulates in the cells of

microbial pathogens, and the accumulation is driven by the membrane

potential (41). "