Viruses and other genetic parasites are present in virtually all forms of life. This chronic condition has led to diverse host cell adaptations such as CRISPR and RNAi, whose functions attenuate these parasites. It is hypothesized that programmed cell death (PCD) is an additional adaptation whose origins reside in viral defense. A core event of apoptotic PCD is the regulated release of mitochondrial inter-membrane space proteins into the cytosol, following which these apoptogenic proteins bring about the demise of the cell. The most well studied example of this is found in animals, where the release of mitochondrial cytochrome C nucleates the formation of the apoptosome, which then activates caspase mediated cell death. The release of mitochondrial proteins contributes to PCD in diverse organisms lacking the apoptosome, indicating that regulated mitochondrial release predates the evolution of canonical apoptosis. Using the budding yeast Saccharomyces cerevisiae, we recently confirmed an early study showing that Nuc1, a homolog of the mitochondrial apoptotic driver protein Endonuclease G, attenuates cytosolic double stranded RNA (dsRNA) viruses, which are endemic to yeast and many other organisms. Viral attenuation by Nuc1 occurs most prominently during meiosis and in association with its developmentally programmed relocation from the mitochondria to the cytosol. Intriguingly, meiotic viral attenuation by Nuc1 occurs within the context of meiotic PCD of the superfluous mother cell that we have also discovered. These findings are discussed here.

Postnatal acquisition of microorganisms from maternal and environmental sources contributes to the child microbiome development. Several studies showed that the mode of delivery and breastfeeding may have impact on the oral bacterial colonization, however, the influence on oral fungal colonization is still unknown. We performed a systematic literature review on mother to child oral fungi transmission, namely regarding the association between the mode of delivery and breastfeeding in oral yeast colonization. Our analysis revealed no significant differences between the oral mycobiome of breastfed and bottle-fed children. As for the delivery mode, the majority of studies found a relation between fungal colonization and vaginal delivery. Candida albicans was the most commonly isolated fungi species. Our analysis suggests that maternal breastfeeding does not seem to influence oral mycology, but vaginal delivery appears to promote oral yeast colonization in early life.

Chlamydia trachomatis is an obligate intracellular pathogen that replicates inside a parasitic vacuole called the inclusion. The nascent inclusion is derived from the host plasma membrane and serves as a platform from which Chlamydia controls interactions with the host microenvironment. To survive inside the host cell, Chlamydia scavenges for nutrients and lipids by recruiting and/or fusing with various cellular compartments. The mechanisms by which these events occur are poorly understood but require host proteins such as the SNARE proteins (SNAP (Soluble N-ethylmaleimide-sensitive factor attachment protein) Receptor). Here, we show that SNAP-23 and Syntaxin 4, two plasma membrane SNAREs, are recruited to the inclusion and play an important role in Chlamydia development. Knocking down SNAP-23 and Syntaxin 4 by CRISPR-Cas9 reduces the amount of infectious progeny. We then demonstrate that the loss of both of these SNARE proteins results in the dysregulation of Chlamydia-induced lipid droplets, indicating that both SNAP-23 and Syntaxin 4 play a critical role in lipid droplet homeostasis during Chlamydia infection. Ultimately, our data highlights the importance of lipid droplets and their regulation in Chlamydia development.

Leishmania parasites are responsible for a range of clinical manifestations ranging from self-resolving cutaneous sores to life-threatening diseases. The management of leishmaniasis is complicated in part by the scarcity of treatment options but also by the emerging or established resistance to available drugs. A major driver of resistance in Leishmania is the amplification of resistance genes taking advantage of the highly repetitive genomic landscape of the parasite. The recent advent of whole genome gain of function screens gave new momentum to the study of such resistance mechanisms, leading to the identification of novel resistance factors and drug targets against approved drugs, which include antimony (SbIII), miltefosine (MIL), paromomycin (PMM), and amphotericin B. However, these screens do not pinpoint single nucleotide variations (SNVs), an important contributor of drug resistance. To fill the gap, our recent study describes the optimization of chemical mutagenesis coupled to next generation sequencing, an approach called Mut-seq, as a way to explore networks of drug resistance genes in organisms with a diploid to mosaic aneuploid genome like Leishmania. Our Mut-seq screen revealed associations between genes linked with lipid metabolism and resistance to MIL, and highlighted the role of a protein kinase in translation leading to resistance to PMM.