Spiramycin Disarms without Inhibiting Growth.

Spiramycin is a 16-membered macrolide antibiotic currently used in therapy to treat infections caused by Gram-positive bacteria responsible for respiratory tract infections, and it is also effective against some Gram-negative bacteria and against spp. In contrast, , which is one of the pathogens of most concern globally, is intrinsically resistant to spiramycin. In this study we show that spiramycin inhibits the expression of virulence determinants in in the absence of any significant effect on bacterial multiplication. In vitro experiments demonstrated that production of pyoverdine and pyocyanin by an environmental strain of was markedly reduced in the presence of spiramycin, as were biofilm formation, swarming motility, and rhamnolipid production. Moreover, treatment of with spiramycin sensitized the bacterium to HO exposure. The ability of spiramycin to dampen the virulence of the strain was confirmed in a animal model. The results demonstrated that when larvae were infected with the mortality after 24 h was >90%. In contrast, when the spiramycin was injected together with the bacterium, the mortality dropped to about 50%. Furthermore, marked reduction in transcript levels of the antimicrobial peptides gallerimycin, gloverin and moricin, and lysozyme was found in larvae infected with and treated with spiramycin, compared to the larvae infected without spiramycin treatment suggesting an immunomodulatory activity of spiramycin. These results lay the foundation for clinical studies to investigate the possibility of using the spiramycin as an anti-virulence and anti-inflammatory drug for a more effective treatment of infections, in combination with other antibiotics.