Blocking the evolution of insecticide-resistant malaria vectors with a microsporidian.

Finding a way to block the evolution insecticide resistance would be a major breakthrough for the control of malaria. We suggest that this may be possible by introducing a stress into mosquito populations that restores the sensitivity of genetically resistant mosquitoes and that decreases their longevity when they are not exposed to insecticide. We use a mathematical model to show that, despite the intense selection pressure imposed by insecticides, moderate levels of stress might tip the evolutionary balance between costs and benefits of resistance toward maintaining sensitivity. Our experimental work with the microsporidian parasite Vavraia culicis infecting two lines of resistant mosquitoes and a sensitive line suggests that it may indeed be possible to stress the mosquitoes in the required way. The mortality of resistant mosquitoes 24 h after exposure to the insecticide was up to 8.8 times higher in infected than in uninfected ones; if mosquitoes were not exposed to the insecticide, resistant mosquitoes infected by the microsporidian lived about half as long as uninfected ones and insecticide-sensitive mosquitoes (with or without the parasite). Our results suggest that biopesticides or other insecticides that interfere with the expression of resistance may help to manage insecticide resistance in programs of malaria control.

Deficiency in the multicopy Sycp3-like X-linked genes Slx and Slxl1 causes major defects in spermatid differentiation.

The human and mouse sex chromosomes are enriched in multicopy genes required for postmeiotic differentiation of round spermatids into sperm. The gene Sly is present in multiple copies on the mouse Y chromosome and encodes a protein that is required for the epigenetic regulation of postmeiotic sex chromosome expression. The X chromosome carries two multicopy genes related to Sly: Slx and Slxl1. Here we investigate the role of Slx/Slxl1 using transgenically-delivered small interfering RNAs to disrupt their function. We show that Slx and Slxl1 are important for normal sperm differentiation and male fertility. Slx/Slxl1 deficiency leads to delay in spermatid elongation and sperm release. A high proportion of delayed spermatids are eliminated via apoptosis, with a consequent reduced sperm count. The remaining spermatozoa are abnormal with impaired motility and fertilizing abilities. Microarray analyses reveal that Slx/Slxl1 deficiency affects the metabolic processes occurring in the spermatid cytoplasm but does not lead to a global perturbation of sex chromosome expression; this is in contrast with the effect of Sly deficiency which leads to an up-regulation of X and Y chromosome genes. This difference may be due to the fact that SLX/SLXL1 are cytoplasmic while SLY is found in the nucleus and cytoplasm of spermatids.