Hi,
In response to your questions, there are a number of researchers
currently looking at this phenomenon (in the context of bacterial
resistance/reduced susceptibility). A few novel ideas/concepts have
come to light in last few years which may also be of interest to you,
and these include :
1: Subpopulations of "quiescent" cells within a given single species
population that may well be in a dormant (or have a reduced metabolic)
state and this may account for the characteristic tailing phenomenon
(of persistent survivors) seen following antimicrobial/antibiotic
treatment (Refs: Henge-
Aronis, 1996; Matin et al., 1989). This state allows bacteria to be
less susceptible to a variety of treatment agents.
2: Multidrug eflux pumps. For example mar and acrAB (George and Levy,
1983; Ma et al., 1993) The mar locus of E.coli was the first mechanism
found to be involved in chromasomally encoded, intrinsic resistance of
Gram negative bacteria to drugs. Homologues have since been described.
3: Suicide-less mutants: Self explanatory really. Kim Lewis (Lewis,
2000; 2001) suggests that the death of bacterial cells following
treatments with bactericidal agents results not from the direct action
of the agent, but from a programmed suicide mechanism. Thus mutants
will be less susceptible to different treatment agents.
4: Specific cross resistance. Simply, the mode of action of one agent
is similar or identical to the mode of another agent and a mutation(s)
or aquisition of specific genetic information will account for the
resistance to both. Examples of this can be found in papers by
Chuanchuen et al., (2001) (cross resistance to Triclosan and
antibiotics) and Sidhu et al. (2001) (QAC and antibiotic cross
resistance).
All the refs. can be easily found in PubMed. I hope this helps,
Regards,
Alex Rickard
Dr. Alex Rickard
School of Pharmacy
University of Manchester
UK
