A specific concentration of chlorpromazine eliminates plasmids from bacteria as a consequence of inhibiting plasmid replication whereas replication of the bacterial genome is unaffected. The effective concentration of the phenothiazine for plasmid elimination depends upon the size of the plasmid; larger plasmids requiring higher concentrations. However, higher concentrations of the compound are required as the plasmid copy number increases. When either the size of the plasmid is very high or the copy number if high, the concentration needed for the inhibition of the plasmid(s) approaches that for the inhibition of the replication of the bacterial genome.
Compounds that are effective and non-toxic and promote the elimination of plasmids from infecting bacteria have a role to play in animal husbandry. Consequently, when a bacterium carrying plasmids that contain antibiotic resistant genes infects cows, the ability to cure the bacterium of these plasmids renders the infecting bacterium susceptible to antibiotics to which it was initially resistant. Because chlorpromazine promotes serious side effects in animals and humans, there is a stringent need for other compounds that are equally effective but without serious side effects.
The problem with the approach you are describing above is that in order to eliminate antibiotic resistance, you really need to have 100% plasmid curing. However plasmid curing with those agents are not very efficient, often just a few percent. So I am skeptical that such an approach would have any real efficacy - especially with persistent antibiotic treatment providing a selective pressure.
I disagree with you. Depending on the size and number of copies of plasmids, you can eliminate completely within one or two generations of plasmids that infect a Gram negative bacterium since these bacteria are extremely resistant to the phenothiazine and hence, the difference in genome size makes it possible. The question asked: any other non-phenothiazine compounds that have plasmid elimination properties. I have found none other than Novobiocin which works well with S. aureus. I suggest the following articles for proof of the statement made, and this is only a partial listing limited to the studies of Joseph Molnar and his many, many colleagues world-wide.
Schelz Z, Martins M, Martins A, Viveiros M, Molnar J, Amaral L. Elimination of
plasmids by SILA compounds that inhibit efflux pumps of bacteria and cancer
cells. In Vivo. 2007 Jul-Aug;21(4):635-9. PubMed PMID: 17708358.
Spengler G, Molnár A, Schelz Z, Amaral L, Sharples D, Molnár J. The mechanism
of plasmid curing in bacteria. Curr Drug Targets. 2006 Jul;7(7):823-41. Review.
PubMed PMID: 16842214.
Wolfart K, Spengler G, Kawase M, Motohashi N, Molnár J, Viveiros M, Amaral L.
Synergistic interaction between proton pump inhibitors and resistance modifiers:
promoting effects of antibiotics and plasmid curing. In Vivo. 2006
May-Jun;20(3):367-72. PubMed PMID: 16724672.
Sharples D, Spengler G, Molnár J, Antal Z, Molnár A, Kiss JT, Szabó JA,
Hilgeroth A, Gallo S, Mahamoud A, Barbe J. The interaction between resistance
modifiers such as pyrido[3,2-g]quinoline, aza-oxafluorene and pregnane
derivatives with DNA, plasmid DNA and tRNA. Eur J Med Chem. 2005
Feb;40(2):195-202. Erratum in: Eur J Med Chem. 2005 Oct;40(10):1070. PubMed PMID:
15694654.
Molnár J, Molnár A, Spengler G, Mándi Y. Infectious plasmid resistance and
efflux pump mediated resistance. Acta Microbiol Immunol Hung. 2004;51(3):333-49.
Review. PubMed PMID: 15571073.
Spengler G, Miczák A, Hajdú E, Kawase M, Amaral L, Molnár J. Enhancement of
plasmid curing by 9-aminoacridine and two phenothiazines in the presence of
proton pump inhibitor 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone. Int J
Antimicrob Agents. 2003 Sep;22(3):223-7. PubMed PMID: 13678825.
Molnár A, Amaral L, Molnár J. Antiplasmid effect of promethazine in mixed
bacterial cultures. Int J Antimicrob Agents. 2003 Sep;22(3):217-22. PubMed PMID:
13678824.
Miskolci C, Labádi I, Kurihara T, Motohashi N, Molnár J. Guanine-cytosine rich
regions of plasmid DNA can be the target in anti-plasmid effect of
phenothiazines. Int J Antimicrob Agents. 2000 Apr;14(3):243-7. PubMed PMID:
10773496.
Motohashi N, Kawase M, Saito S, Miskolci C, Berek L, Molnár J. Plasmid
elimination and immunomodulation by 3-benzazepines in vitro. Anticancer Res. 1999
Nov-Dec;19(6B):5075-8. PubMed PMID: 10697513.
Motohashi N, Kurihara T, Kawase M, Hevér A, Tanaka M, Szabo D, Nacsa J,
Yamanaka W, Kerim A, Molnár J. Drug resistance reversal, anti-mutagenicity and
antiretroviral effect of phthalimido- and chloroethyl-phenothiazines. Anticancer
Res. 1997 Sep-Oct;17(5A):3537-43. PubMed PMID: 9413199.
Molnár J. New drug effects on bacteria, the antiplasmid effect. Acta
Microbiol Immunol Hung. 1997;44(1):21-6. Review. PubMed PMID: 9284975.
Barbe J, Mándi Y, Hevér A, Petri I, Galy JP, Molnár J. Effects of acridines
on bacterial plasmid replication and endotoxin. In Vivo. 1996
Nov-Dec;10(6):601-6. PubMed PMID: 8986470.
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