Behind the paper

Share the real story behind your paper, from conception to publication, the highs and the lows.

Contributor

Highway into the brain: a mouse model to study newborn neurolisteriosis

Bacterial infections of the central nervous system (CNS) are devastating with neonates being the population at the highest risk. Preventive measures, such as hygiene regimens and antibiotic intrapartum prophylaxis have decreased the incidence of neonatal CNS infections. However, mortality rates remain substantial and serious long-term sequelae, such as deafness or mental retardation are frequently observed. Knowledge about the pathogenesis CNS infection as a result of mucosal pathogen exposure is scant, mostly because of a lack of suitable animal models. And that´s where our story started…
Go to the profile of Marcus Fulde
Oct 15, 2018
Contributor

Growers: Hard to kill

Last year, tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) killed 1.5 million people, overtaking HIV/ AIDS – this reflects massive advances in treatment of HIV, which haven’t been matched in the treatment of TB. Although almost all cases of TB are curable, the treatment is extremely long, and no progress has been made in shortening treatment in 40 years, since the introduction of the drug rifampicin: which reduced the regimen duration from 18 to 6 months.
Go to the profile of Babak Javid
Oct 11, 2018
Contributor

The type VI secretion system under tension

The development of new approaches is often challenging, but is also critical to gain further insights that cannot be accessed by existing methods or technologies. In this study, we borrowed a technique initially developed by the group of Alice Ting for studies in eukaryotic cells and mitochondria. This technique is based on the covalent biotinylation of proteins at the proximity of an engineered variant of the soybean ascorbate peroxidase, called APEX2. Biotinylated proteins can be then enriched and identified by mass spectrometry. We adapted this technique in Escherichia coli cells in order to identify partners of the highly dynamic TssA protein that is involved in the different stages of the assembly of the Type VI secretion system (T6SS). The T6SS is a fascinating machine widespread in Gram-negative bacteria. It assembles a spring-like structure that can be compared to a crossbow or speargun, and used to inject effectors into target cells upon contraction. The APEX2 approach did not only allow to provide further insights on the assembly pathway of this multiprotein apparatus but also revealed a new player in T6SS that acts as a latch for the nano-crossbow.
Go to the profile of Yoann Santin
Oct 01, 2018
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Approaching HIV prevention with young women’s preferences in mind

To many scientists, it may seem that HIV prevention research has succeeded – large clinical trials of oral pre-exposure prophylaxis (PrEP) and vaginal formulations of antiretroviral drugs (ARVs) demonstrated that these products can indeed prevent HIV infection when used [1-3]. This is great news! But the problem we face as a global HIV prevention community is not whether or not we have efficacious products. The problem is whether or not the products will appropriately meet women’s needs and lifestyles and thus whether or not women will use them. Adherence to product use is quite possibly the biggest issue blocking the eradication of sexual HIV transmission [4].
Go to the profile of Nina Derby
Sep 24, 2018
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Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements

Infants are affected by the antibiotic resistance crisis and carry more resistant bacteria in their gut than adults, irrespective of whether they have been treated with antibiotics or not. It has been unclear where these bacteria come from and if the maternal gut microbiota and breast milk contribute to the assembly of the gut resistome in early life.
Go to the profile of Katariina Parnanen
Sep 24, 2018
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Intestinal inflammation Salmonella style

It has been long known that intestinal inflammation is central for the pathology that follows infection with non-typhoidal Salmonellae such as Salmonella Typhimurium. However, in recent years work carried out in the laboratories of Wolf-Dietrich Hardt and Andreas Baumler have established that the inflammatory response is also required for Salmonella Typhimurium to compete with the resident intestinal microbiota and to secure essential nutrients. Unlike most other tissues, where the mere presence of bacterial products capable of stimulating innate immune receptors can trigger inflammation, the intestinal tract presents a challenge to those pathogens that need inflammation to sustain their livelihood. Indeed, the presence in the intestinal tract of an abundance of microbial products with the potential to stimulate innate immune receptors demands for the intestinal epithelium to be subject to negative regulatory mechanisms that can prevent the pathology that could result from the indiscriminate firing of these receptors. In fact, misregulation of those mechanisms can result in chronic inflammatory conditions such as inflammatory bowel disease. Consequently, to initiate an inflammatory response in the gut, S. Typhimurium cannot relay on the stimulation of innate immune receptors by the standard “pathogen-associated molecular patterns” (e. g LPS, peptidoglycan, flagellin) that, like many other bacteria, posses in abundance. Therefore, the mechanisms by which Salmonella trigger intestinal inflammation have been a long-standing question in the field and have been the subject of some controversy. We believe that a paper that we recently published in Nature Microbiology has finally clarified this important issue.
Go to the profile of Jorge Galan
Sep 17, 2018
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A loopy signature- Tracing HIV-1 strains that imprint broadly neutralising antibody responses

According to the WHO, almost a million people die each year of HIV-related causes across the world. Although numbers are falling, most experts agree that a vaccination against HIV will be required to stop the pandemic once and for all. The Holy Grail is a vaccine that induces broadly neutralizing antibodies (bnAbs), which inhibit the majority of circulating HIV strains. Thus far, all efforts to develop such a vaccine have failed. In a recent study we show that the genome of the infecting virus strongly determines how our body immune defences respond to it. Some HIV strains even seem to be able to induce broadly neutralizing antibody responses across individuals - exactly what is needed to develop a successful vaccine
Go to the profile of Alexandra Trkola
Sep 10, 2018
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The real soil microbiomes and their roles in vegetation transformation as uncovered in the Cerrado

Soil organisms, particularly members of the soil microbiome, regulate plant performance and control plant communities. In our study, we show that the microbiome complexity increases from early successional to climax vegetation. We also found an enrichment of animal parasites and plant pathogens in early successional compared to later successional vegetation. Together, our results suggest that soil organisms, particularly plant pathogens, facilitate plant succession, while the most complex microbiomes keep plant communities in climax vegetation stable. Therefore, our results point at the importance of soil microorganisms for plant vegetation dynamics and stability.
Go to the profile of Stefan Geisen
Sep 06, 2018
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Using basic research in insect biology to fight disease

Many of the world’s most serious diseases are caused by pathogens that are transmitted to people by insects. Reductions in cases and deaths of these diseases have been achieved largely by using insecticides, but resistance to these chemicals now threatens those advances. Here we underline how basic research into insect biology is informing the development of new ways to control disease via targeting insect populations.
Go to the profile of W. Robert Shaw
Aug 28, 2018
Contributor

Divide and Conquer: How malaria parasites use divergent means to modify its host cell

Human malaria parasites are able to pull off a stunning trick inside our bodies. At the point at which the major disease symptoms are observed, the parasites hide inside red blood cells (RBCs); cells that are terminally differentiated and contain no nuclei or organelles that the parasite could subvert to its own ends. In addition, during the course of circulation the spleen routinely investigates RBCs and destroys those that show signs of structural damage. The trick the parasite pulls off is the ability to survive, and indeed thrive, within a cell that for all intents and purposes appears to be overtly inhospitable. Once within the cell, the parasite also establishes multiple membrane barriers (the inner parasite membrane and the outer parasitophorous vacuole membrane (PVM)) between itself and the host cell cytoplasm, therefore rendering intraerythrocytic survival even more problematic. The parasite overcomes these biological obstacles by means of a simple barcode. This signal, reported by two independent groups in 2004, is termed the Plasmodium Export Element or PEXEL. At its core, the PEXEL is a substrate for an export-licensing enzyme with the parasite endoplasmic reticulum known as Plasmepsin V or PMV. The PEXEL is found at the N-terminus of a protein following a predicted hydrophobic region (predominantly the signal sequence). Its cleavage by PMV results in the now-matured protein being exported beyond the parasitophorous vacuole and into the host cell cytoplasm. These exported proteins dramatically modify the environment of the host erythrocyte to create a niche suitable for parasite survival. We attempted to answer a critical question in disease pathogenesis involving the very beginning of this pathway. How are PEXEL-containing proteins recognised by Plasmepsin V? Using a proteomics based approach; we identified specific ER proteins that interact with PMV. The first of these, SPC25, provided the link between PMV and the protein entry site at the ER, the Sec61 translocon. Interestingly, this translocon was supplemented with an auxiliary partner protein Sec62, which converts the co-translational translocon to a post-translational form. This addition, as we identified, creates a new requirement for a distinct subset of PEXEL proteins to be fully translated in the parasite cytoplasm before being imported into the ER for PEXEL cleavage. We also discovered that the catalytic signal peptidase, which removes signal sequences, is not involved in this process and is also not associated with PMV in any form. This paper can be found here at Nature MIcrobiology: https://doi.org/10.1038/s41564-018-0219-2 In trying to answer a single question, we ended up answering several queries that had been nagging the malaria field. It also opened up exciting new avenues for exploration. What is the molecular mechanism by which Sec62 interacts with PEXEL proteins? Does it act as a direct PEXEL detector or is there an intermediary in this process? Does the translocon that imports PEXEL proteins contain novel components that could give us new insight into post-translational protein translocation? What happens to the mature PEXEL protein post-PMV cleavage? We believe that answering these questions will provide valuable information about the mechanism by which the most deadly human parasite causes disease.
Go to the profile of Danushka Marapana
Aug 26, 2018