Tricky Tryps African trypanosomes, responsible for human sleeping sickness, are known for their powerful strategies of immune evasion, in particular antigenic variation. Adding another facet to this adaptive potential, Salmon et al. (p. 463 , published online 14 June; see the cover) now show that early after infection, these parasites subvert the first line of innate host defense by inhibiting tumor necrosis factor-α synthesis in myeloid cells. This occurs through the stress-induced synthesis and release of cyclic adenosine monophosphate by phagocytosed parasites. The findings provide a long-sought function for the abundant and diverse adenylate cyclases in salivarian trypanosomes. Furthermore, this altruistic host colonization strategy, in which a proportion of parasites are sacrificed so that others can thrive, also highlights the selective advantage of population behavior in infection.

SummaryAntigenic variation of the parasite Trypanosoma brucei operates by monoallelic expression of a variant surface glycoprotein (VSG) from a collection of multiple telomeric expression sites (ESs). Each of these ESs harbours a long polycistronic transcription unit containing several expression site-associated genes (ESAGs). ESAG4 copies encode bloodstream stagespecific adenylyl cyclases (AC) and belong to a larger gene family of around 80 members, the majority of which, termed genes related to ESAG4 (GRESAG4s), are not encoded in ESs and are expressed constitutively in the life cycle. Here we report that ablation of ESAG4 from the active ES did not affect parasite growth, neither in culture nor upon rodent infection, and did not significantly change total AC activity. In contrast, inducible RNAi-mediated knock-down of an AC subfamily that includes ESAG4 and two ESAG4-like GRESAG4 (ESAG4L) genes, decreased total AC activity and induced a lethal phenotype linked to impaired cytokinesis. In the Desag4 line compensatory upregulation of apparently functionally redundant ESAG4L genes was observed, suggesting that the ESAG4/ESAG4L-subfamily ACs are involved in the control of cell division. How deregulated adenylyl cyclases or cAMP might impair cytokinesis is discussed.

The Wallemiomycetes includes three species of molds from the genus Wallemia . These fungi are adapted to environments of high osmotic stress, contaminate various foods, cause respiratory disease, and have an unusual mode of asexual reproduction. Wallemia was recently proposed as a new class based on 18S ribosomal RNA gene sequences to accommodate the isolated position of the clade in the Basidiomycota. We analyzed the phylogenetic position of the Wallemiomycetes using 3451 nucleotide characters of the 18S, 25S, and 5.8S ribosomal RNA genes and 1282 amino acid positions of rpb1, rpb2, and tef1 nuclear protein-coding genes across 91 taxa. Different gene regions and methods of phylogenetic inference produce mildly conflicting placements of the Wallemiomycetes. Parsimony analyses of nrDNA data suggest that the Wallemiomycetes is an early diverging lineage of Basidiomycota, occupying a basal position near the Entorrhizomycetidae. Ultrastructural data, some Bayesian analyses, and amino acid sequences suggest the Wallemiomycetes may be the sister group of the Agaricomycotina or Ustilaginomycotina. The combined gene tree supports the Wallemiomycetes as a lineage basal to a core clade of Pucciniomycotina, Ustilaginomycotina, and Agaricomycotina with robust measures of branch support. This study reinforces the isolated position of Wallemia in the Basidiomycota using molecular data from six nuclear genes. In total, five major lineages of Basidiomycota are recognized: the Agaricomycotina, Ustilaginomycotina, Pucciniomycotina, Entorrhizomycetidae, and the Wallemiomycetes.