induced, non-mutational efflux-based resistance in bacteria?

April 21, 2007

I've been aware that P. aeruginosa and Mtb can up-reg their efflux

pumps by at least ~10x when assaulted by abx. I say at least because

these may have been short term experiments. I'm not sure if the 10x

up-reg was enough to significantly change resistance.

A new PLoS One paper (free) says:

" We have previously demonstrated that it is possible to induce

high-level resistance to tetracycline (TET) in susceptible Escherichia

coli K-12 by a gradual, step-wise increase in the exposure to the

antibiotic [5]. The induction process takes about 110 days and this

resistance can be reversed by either transfer to drug free medium or

by the use of Phe-Arg-napthylamide (PA & #946;N), an inhibitor of the AcrAB

efflux pump system [3]–[5]. "

Someone might want to study ref 5 and see if their work is any good.

I'm not really interested enough to read it: right now my

thoughts/instincts/prejudices are telling me to fire away with my

heavy abx combos without pause, rather than pulsing. I'm thinking that

with slow-growing bacteria the only way to kill them may be to wear

them down relentlessly over a long period of time. Yet it's also

possible that pulsing could have some virtues. Too bad it's all

sooooooo speculative in the end. For me, my biggest improvements

(during summer 2005) came during generous use of doxy and tini without

any breaks that I can recall... certainly none more than a few days

long, if any.

Ah jeez, I broke down and took a quick look at ref 5. It's free:

0

Looks like the tetracycline resistance they obtained was 6-fold (in

terms of the MIC). Resistance to other abx was simultaneously obtained

(presumably because one or more of the efflux pumps induced was a

nonspecific one): mostly around 4-fold changes in MIC. I would say

these changes are probably kind of borderline in practical importance.

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