In vitro Susceptibility of Prototheca spp. to Antimicrotubular Agents: Preliminary Results, Perspectives and Proposal for a Screening Method.Antimicrob Agents Chemother. 2019 Dec 23 [Online ahead of print]AA
Microorganisms belonging to the Prototheca genus are achlorophyllous microalgae, occasionally behaving as environmental pathogens that cause severe mastitis in milking cows as well as localized or systemic infections in humans and animals. Among the different species belonging to the genus, P. zopfii genotype 2 (recently re-classified as P. bovis) and P. blaschkeae are more commonly associated to bovine mastitis. To date, no pharmacological treatment is available to cure protothecal mastitis and infected animals must be quarantined to avoid spreading of the infection. The few antibiotic and antifungal drugs effective in vitro against Prototheca give poor results in vivo This failure is likely due to the lack of specificity of such drugs. Being microalgae more related to plants than to bacteria or fungi, an alternative possibility is to test molecules with herbicidal properties. In particular, antimicrotubular herbicides for which plant rather than animal tubulin is the selective target. Once a suitable test protocol was set up, a panel of eleven antimicrotubular agents, belonging to different chemical classes and selective for plant tubulin, was tested for the ability to inhibit growth of Prototheca cells in vitro Two dinitroanilines, dinitramine and chloralin, showed a strong inhibitory effect on P. blaschkeae, at low micromolar concentrations, with IC50 of 4.5 and 3 μM, respectively, while both P. zopfii genotype 1 (now re-classified as P. ciferrii) and P. bovis showed susceptibility to dinitramine only, with different degrees. Suitable screening protocols for antimitotic agents are suggested.