Structure–function analysis reveals that the Pseudomonas aeruginosa Tps4 two-partner secretion system is involved in CupB5 translocation

Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium, synonymous with cystic fibrosis patients, which can cause chronic infection of the lungs. This pathogen is a model organism to study biofilms: a bacterial population embedded in an extracellular matrix that provide protection from environmental pressures and lead to persistence. A number of Chaperone-Usher Pathways, namely CupA-CupE, play key roles in these processes by assembling adhesive pili on the bacterial surface. One of these, encoded by the cupB operon, is unique as it contains a nonchaperone-usher gene product, CupB5. Two-partner secretion (TPS) systems are comprised of a C-terminal integral membrane β-barrel pore with tandem N-terminal POTRA (POlypeptide TRansport Associated) domains located in the periplasm (TpsB) and a secreted substrate (TpsA). Using NMR we show that TpsB4 (LepB) interacts with CupB5 and its predicted cognate partner TpsA4 (LepA), an extracellular protease. Moreover, using cellular studies we confirm that TpsB4 can translocate CupB5 across the P. aeruginosa outer membrane, which contrasts a previous observation that suggested the CupB3 P-usher secretes CupB5. In support of our findings we also demonstrate that tps4/cupB operons are coregulated by the RocS1 sensor suggesting P. aeruginosa has developed synergy between these systems. Furthermore, we have determined the solution-structure of the TpsB4-POTRA1 domain and together with restraints from NMR chemical shift mapping and in vivo mutational analysis we have calculated models for the entire TpsB4 periplasmic region in complex with both TpsA4 and CupB5 secretion motifs. The data highlight specific residues for TpsA4/CupB5 recognition by TpsB4 in the periplasm and suggest distinct roles for each POTRA domain.     

AFN-1252 is a potent inhibitor of enoyl-ACP reductase from Burkholderia pseudomallei—Crystal structure,mode of action,and biological activity

Melioidosis is a tropical bacterial infection caused by Burkholderia pseudomallei (B. pseudomallei; Bpm), a Gram-negative bacterium. Current therapeutic options are largely limited to trimethoprim-sulfamethoxazole and β-lactam drugs, and the treatment duration is about 4 months. Moreover, resistance has been reported to these drugs. Hence, there is a pressing need to develop new antibiotics for Melioidosis. Inhibition of enoyl-ACP reducatase (FabI), a key enzyme in the fatty acid biosynthesis pathway has shown significant promise for antibacterial drug development. FabI has been identified as the major enoyl-ACP reductase present in B. pseudomallei. In this study, we evaluated AFN-1252, a Staphylococcus aureus FabI inhibitor currently in clinical development, for its potential to bind to BpmFabI enzyme and inhibit B. pseudomallei bacterial growth. AFN-1252 stabilized BpmFabI and inhibited the enzyme activity with an IC₅₀ of 9.6 nM. It showed good antibacterial activity against B. pseudomallei R15 strain, isolated from a melioidosis patient (MIC of 2.35 mg/L). X-ray structure of BpmFabI with AFN-1252 was determined at a resolution of 2.3 Å. Complex of BpmFabI with AFN-1252 formed a symmetrical tetrameric structure with one molecule of AFN-1252 bound to each monomeric subunit. The kinetic and thermal melting studies supported the finding that AFN-1252 can bind to BpmFabI independent of cofactor. The structural and mechanistic insights from these studies might help the rational design and development of new FabI inhibitors.     

Stable isotopes reveal links between human food inputs and urban ant diets

The amount of energy consumed within an average city block is an order of magnitude higher than that consumed in any other ecosystem over a similar area. This is driven by human food inputs, but the consequence of these resources for urban animal populations is poorly understood. We investigated the role of human foods in ant diets across an urbanization gradient in Manhattan using carbon and nitrogen stable isotopes. We found that some—but not all—ant species living in Manhattan''s most urbanized habitats had δ¹³C signatures associated with processed human foods. In particular, pavement ants (Tetramorium sp. E) had increased levels of δ¹³C similar to δ¹³C levels in human fast foods. The magnitude of this effect was positively correlated with urbanization. By contrast, we detected no differences in δ¹⁵N, suggesting Tetramorium feeds at the same trophic level despite shifting to human foods. This pattern persisted across the broader ant community; species in traffic islands used human resources more than park species. Our results demonstrate that the degree urban ants exploit human resources changes across the city and among species, and this variation could play a key role in community structure and ecosystem processes where human and animal food webs intersect.     

Every inch a finch: a commentary on Grant (1993) ‘Hybridization of Darwin's finches on Isla Daphne Major,Galapagos’

One of the most familiar features of the natural world is that most animals and plants fall into distinct categories known as species. The attempt to understand the nature of species and the origin of new species was the enterprise that drove the early development of evolutionary biology and has continued to be a major focus of research. Individuals belonging to the same species usually share a distinctive appearance and way of life, and they can mate together successfully and produce viable offspring. New species may evolve, therefore, either through ecological divergence or through sexual isolation. The balance between these processes will depend on the extent of hybridization, especially in the early stages of divergence. Detecting and measuring hybridization in natural populations, however, requires intensive, long-term field programmes that are seldom undertaken, leaving a gap in our understanding of species formation. The finch community of a small, isolated island in the Galapagos provided an opportunity to discover how frequently hybridization takes place between closely related species in a pristine location, and Peter Grant''s paper, published in Philosophical Transactions B in 1993, reports the observations that he and his collaborators made during the first 20 years of what is now one of the classical studies of evolution in action. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.     

The early evolution of land plants,from fossils to genomics: a commentary on Lang (1937) ‘On the plant-remains from the Downtonian of England and Wales'

During the 1920s, the botanist W. H. Lang set out to collect and investigate some very unpromising fossils of uncertain affinity, which predated the known geological record of life on land. His discoveries led to a landmark publication in 1937, ‘On the plant-remains from the Downtonian of England and Wales’, in which he revealed a diversity of small fossil organisms of great simplicity that shed light on the nature of the earliest known land plants. These and subsequent discoveries have taken on new relevance as botanists seek to understand the plant genome and the early evolution of fundamental organ systems. Also, our developing knowledge of the composition of early land-based ecosystems and the interactions among their various components is contributing to our understanding of how life on land affects key Earth Systems (e.g. carbon cycle). The emerging paradigm is one of early life on land dominated by microbes, small bryophyte-like organisms and lichens. Collectively called cryptogamic covers, these are comparable with those that dominate certain ecosystems today. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.     

Potential effects of warmer worms and vectors on onchocerciasis transmission in West Africa

Development times of eggs, larvae and pupae of vectors of onchocerciasis (Simulium spp.) and of Onchocerca volvulus larvae within the adult females of the vectors decrease with increasing temperature. At and above 25°C, the parasite could reach its infective stage in less than 7 days when vectors could transmit after only two gonotrophic cycles. After incorporating exponential functions for vector development into a novel blackfly population model, it was predicted that fly numbers in Liberia and Ghana would peak at air temperatures of 29°C and 34°C, about 3°C and 7°C above current monthly averages, respectively; parous rates of forest flies (Liberia) would peak at 29°C and of savannah flies (Ghana) at 30°C. Small temperature increases (less than 2°C) might lead to changes in geographical distributions of different vector taxa. When the new model was linked to an existing framework for the population dynamics of onchocerciasis in humans and vectors, transmission rates and worm loads were projected to increase with temperature to at least 33°C. By contrast, analyses of field data on forest flies in Liberia and savannah flies in Ghana, in relation to regional climate change predictions, suggested, on the basis of simple regressions, that 13–41% decreases in fly numbers would be expected between the present and before 2040. Further research is needed to reconcile these conflicting conclusions.     

The impact of climate change on the geographical distribution of two vectors of Chagas disease: implications for the force of infection

Chagas disease, caused by the parasite Trypanosoma cruzi, is the most important vector-borne disease in Latin America. The vectors are insects belonging to the Triatominae (Hemiptera, Reduviidae), and are widely distributed in the Americas. Here, we assess the implications of climatic projections for 2050 on the geographical footprint of two of the main Chagas disease vectors: Rhodnius prolixus (tropical species) and Triatoma infestans (temperate species). We estimated the epidemiological implications of current to future transitions in the climatic niche in terms of changes in the force of infection (FOI) on the rural population of two countries: Venezuela (tropical) and Argentina (temperate). The climatic projections for 2050 showed heterogeneous impact on the climatic niches of both vector species, with a decreasing trend of suitability of areas that are currently at high-to-moderate transmission risk. Consequently, climatic projections affected differently the FOI for Chagas disease in Venezuela and Argentina. Despite the heterogeneous results, our main conclusions point out a decreasing trend in the number of new cases of Tr. cruzi human infections per year between current and future conditions using a climatic niche approach.     

Sex ratio variation shapes the ecological effects of a globally introduced freshwater fish

Sex ratio and sexual dimorphism have long been of interest in population and evolutionary ecology, but consequences for communities and ecosystems remain untested. Sex ratio could influence ecological conditions whenever sexual dimorphism is associated with ecological dimorphism in species with strong ecological interactions. We tested for ecological implications of sex ratio variation in the sexually dimorphic western mosquitofish, Gambusia affinis. This species causes strong pelagic trophic cascades and exhibits substantial variation in adult sex ratios. We found that female-biased populations induced stronger pelagic trophic cascades compared with male-biased populations, causing larger changes to key community and ecosystem responses, including zooplankton abundance, phytoplankton abundance, productivity, pH and temperature. The magnitude of such effects indicates that sex ratio is important for mediating the ecological role of mosquitofish. Because both sex ratio variation and sexual dimorphism are common features of natural populations, our findings should encourage broader consideration of the ecological significance of sex ratio variation in nature, including the relative contributions of various sexually dimorphic traits to these effects.     

The trophic responses of two different rodent–vector–plague systems to climate change

Plague, the causative agent of three devastating pandemics in history, is currently a re-emerging disease, probably due to climate change and other anthropogenic changes. Without understanding the response of plague systems to anthropogenic or climate changes in their trophic web, it is unfeasible to effectively predict years with high risks of plague outbreak, hampering our ability for effective prevention and control of the disease. Here, by using surveillance data, we apply structural equation modelling to reveal the drivers of plague prevalence in two very different rodent systems: those of the solitary Daurian ground squirrel and the social Mongolian gerbil. We show that plague prevalence in the Daurian ground squirrel is not detectably related to its trophic web, and that therefore surveillance efforts should focus on detecting plague directly in this ecosystem. On the other hand, plague in the Mongolian gerbil is strongly embedded in a complex, yet understandable trophic web of climate, vegetation, and rodent and flea densities, making the ecosystem suitable for more sophisticated low-cost surveillance practices, such as remote sensing. As for the trophic webs of the two rodent species, we find that increased vegetation is positively associated with higher temperatures and precipitation for both ecosystems. We furthermore find a positive association between vegetation and ground squirrel density, yet a negative association between vegetation and gerbil density. Our study thus shows how past surveillance records can be used to design and improve existing plague prevention and control measures, by tailoring them to individual plague foci. Such measures are indeed highly needed under present conditions with prevailing climate change.     

The impact of maternal infection with Mycobacterium tuberculosis on the infant response to bacille Calmette–Guérin immunization

Bacille Calmette–Guérin (BCG) immunization provides variable protection against tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. We therefore hypothesized that maternal latent Mycobacterium tuberculosis infection (LTBI) influences infant responses to BCG immunization at birth. We measured antibody (n = 53) and cellular (n = 31) responses to M. tuberculosis purified protein derivative (PPD) in infants of mothers with and without LTBI, in cord blood and at one and six weeks after BCG. The concentrations of PPD-specific antibodies declined between birth (median [interquartile range (IQR)]) 5600 ng ml⁻¹ [3300–11 050] in cord blood) and six weeks (0.00 ng ml⁻¹ [0–288]). Frequencies of PPD-specific IFN-γ-expressing CD4⁺T cells increased at one week and declined between one and six weeks (p = 0.031). Frequencies of IL-2- and TNF-α-expressing PPD-specific CD4⁺T cells increased between one and six weeks (p = 0.019, p = 0.009, respectively). At one week, the frequency of PPD-specific CD4⁺T cells expressing any of the three cytokines, combined, was lower among infants of mothers with LTBI, in crude analyses (p = 0.002) and after adjusting for confounders (mean difference, 95% CI −0.041% (−0.082, −0.001)). In conclusion, maternal LTBI was associated with lower infant anti-mycobacterial T-cell responses immediately following BCG immunization. These findings are being explored further in a larger study.