The preferential inhibition of Bacillus subtilis spore outgrowth by chloroquine

Abstract

Chloroquine inhibited the outgrowth of Bacillus subtilis spores at a 10-fold lower concentration than that required to prevent vegetative growth. Analysis of macromolecular synthesis in outgrowing spores and vegetative cells in the presence of chloroquine indicated that it acted preferentially on transcription. Differential sensitivity of outgrowing spores and vegetative cells to chloroquine was not due to changes in the specificity of the RNA-polymerase, since RNA-polymerase activity measured in permeabilized cells was not affected differently by the drug. The preferential inhibition of spore outgrowth was not evident at pH 8.0, at which the majority of chloroquine is in a monovalent, more lipophilic, form. In the presence of inhibitors affecting membrane potential, vegetative cells were as sensitive to chloroquine as outgrowing spores. Measurement of [14C]-chloroquine uptake showed that early outgrowing spores accumulated twice as much drug as resistant late outgrowing spores and seven times more than vegetative cells. Treatment of vegetative cells with metabolic inhibitors led them to accumulate chloroquine to the levels found in outgrowing spores. Therefore, the preferential inhibition of outgrowing spores by chloroquine is the result of increased uptake of the drug, reflecting differences in energy metabolism from vegetative cells.

Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America

“…Chloroquine inhibits DNA and RNA polymerase activity in vitro [13], halts the replication of Legionella pneumophila by limiting the availability of iron necessary for intracellular growth [14], and has weak antibacterial properties [15] against Salmonella sp. [16] and Bacillus subtilis [17].…”

Caffeic Acid Activity Against Clostridium botulinum Spores

“…Although bacterial spores may remain viable under extreme environmental conditions, germination may be inhibited by minor physical or chemical changes (Gould et al, 1970;Halvorson et al, 1966). Relatively small amounts of a chemical agent can be sporostatic, yet considerably higher concentrations are required to render spores non-viable or to inhibit vegetative cell growth (Bowles, 1991;Bowles and Miller 1993a,b;Smith and Dawes, 1989).…”

Quinine sulfate and bacterial invasion

“…Apart from their well-documented advantages, i.e., excellent bioavailability, low toxicity, long-term safety, and low-cost, one more property of these drugs might be of special interest in the setting of HIV infection and of autoimmune diseases, namely, their ability to prevent/treat several infectious diseases other than malaria. The antimalarials have been proven as being beneficial for several intracellular pathogens, but only intracellular ones that mainly affect individuals with impaired cell-mediated immunity, such as Legionella pneumophila, Histoplasma capsulatum, Francisella tularensis, Penicillium marneffei Cryptococcus neoformans, Bacillus subtilis, Mycobacterium avium, Mycobacterium tuberculosis, Toxoplasma gondii [13-20] and others.…”