Effects of the microbicide ceragenin CSA‐13 on and properties ofBacillus subtilisspores prepared on two very different media

Abstract

Aims To determine how the microbicide ceragenin‐13 (CSA‐13) kills Bacillus subtilis spores prepared on growth or sporulation media, and these spores’ properties. Methods and Results Spores made on Luria broth (LB) growth or double‐strength Schaeffer’s‐glucose (2xSG) sporulation plates found that spores made on LB plates have coat defects as evidenced by their lower hypochlorite resistance, faster germination with dodecylamine and slower germination with Ca2+‐dipicolinic acid (CaDPA) than 2xSG plate spores. CSA‐13 triggered CaDPA release from spores, an early step in germination, but only well at 70°C and better with spores made on LB than on 2xSG plates. Approximately 90% of spores with elevated levels of SpoVA proteins that form a CaDPA release channel, released CaDPA with CSA‐13 at 70°C, and faster with spores made on LB than 2xSG plates. Levels of CSA‐13 killing of spores made on LB and 2xSG plates were similar to levels of CaDPA release triggered by this agent. Conclusions CSA‐13 kills bacterial spores, but only at high concentrations and temperatures, and is preceded by CaDPA release. Significance and Impact of the Study CSA‐13 is not a direct sporicide as reported previously, but most likely germinates spores via activation of spores’ CaDPA channel, albeit inefficiently, and then killing the germinated spores.

From Marine Metabolites to the Drugs of the Future: Squalamine, Trodusquemine, Their Steroid and Triterpene Analogues

“…These results were confirmed in the porcine model of burn wounds with ceragenin 186b [243]. Another hard-to-fight pathogen, B. subtilis spores, is also sensitive to CSA-13 186a treatment [244,245].…”

Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant Enterococcus spp.

“…There are several in vitro and in vivo studies about the successful antimicrobial activities of ceragenins against various Gram-negative and Gram-positive bacteria, some yeast such as Candida albicans, and some parasites such as Trichomonas vaginalis. These studies showed that CSAs have broad spectrum antimicrobial activities against not only planktonic cells but also the biofilms or spore forms of the microorganisms, and CSA-13 and CSA-131 in particular were found to be the most potent agents [19][20][21][22]. Additionally, a recent study has shown that CSA-44 inhibited biofilm formation and decreased the biofilm mass formed by E. faecalis and C. albicans on teeth and dental composite surfaces [23].…”