Developmental trajectory of the healthy human gut microbiota during the first 5 years of life

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Emerging concepts in the pathogenesis of the Streptococcus pneumoniae: From nasopharyngeal colonizer to intracellular pathogen

Streptococcus pneumoniae (the pneumococcus) is a human respiratory tract pathogen and a major cause of morbidity and mortality globally. Although the pneumococcus is a commensal bacterium that colonizes the nasopharynx, it also causes lethal diseases such as meningitis, sepsis, and pneumonia, especially in immunocompromised patients, in the elderly, and in young children. Due to the acquisition of antibiotic resistance and the emergence of nonvaccine serotypes, the pneumococcus has been classified as one of the priority pathogens for which new antibacterials are urgently required by the World Health Organization, 2017. Understanding molecular mechanisms behind the pathogenesis of pneumococcal infections and bacterial interactions within the host is crucial to developing novel therapeutics. Previously considered to be an extracellular pathogen, it is becoming evident that pneumococci may also occasionally establish intracellular niches within the body to escape immune surveillance and spread within the host. Intracellular survival within host cells also enables pneumococci to resist many antibiotics. Within the host cell, the bacteria exist in unique vacuoles, thereby avoiding degradation by the acidic lysosomes, and modulate the expression of its virulence genes to adapt to the intracellular environment. To invade and survive intracellularly, the pneumococcus utilizes a combination of virulence factors such as pneumolysin (PLY), pneumococcal surface protein A (PspA), pneumococcal adhesion and virulence protein B (PavB), the pilus‐1 adhesin RrgA, pyruvate oxidase (SpxB), and metalloprotease (ZmpB). In this review, we discuss recent findings showing the intracellular persistence of Streptococcus pneumoniae and its underlying mechanisms.     

Micropurification and amino acid sequence of β-casomorphin-8 in milk from a woman with postpartum psychosis

Milk was obtained from a woman with acute postpartum psychosis and with ongoing lactation. Defatted samples were subjected to micropurification and collected fractions were analyzed by means of their β-casomorphin-8 immunoreactivity. Immunoreactive material with the same chromatographic properties as synthetic human β-casomorphin-8 was determined by amino acid sequence analysis to be Tyr-Pro-Phe-Val-Glu-Pro-Ile-Pro. Its molecular mass was determined by fast atom bombardment-mass spectrometry to be 962.3 Da. These determinations, which ultimately identify the immunoreactive material as human β-casomorphin-8, represent the first structural identification of a β-casomorphin peptide from a body fluid.     

Genetic diversity is retained in a bottlenecked Cinereous Vulture population in Turkey

Vulture populations worldwide have suffered precipitous declines in recent decades. The Cinereous Vulture Aegypius monachus, a highly philopatric scavenger distributed across southern Europe and the central Asian plateau, is threatened in many parts of its range. Turkey holds the second largest population of this species in the Western Palaearctic, but there has been no research on its genetic structure and the possible implications of this structure for the future of the species. Here we report nuclear diversity and relatedness determined by short tandem repeat genotyping of 81 individuals from the four largest colonies. Our results demonstrated no significant genetic structuring, suggesting a single panmictic metapopulation connected by frequent dispersal. Furthermore, we show that the study population has retained moderate levels of genetic diversity, despite passing through a recent demographic bottleneck. We estimated the effective population size to be 112 individuals (95% confidence interval 74–201). Our results imply that the observed lack of increase in population size since the 1990s has not been caused by lowered fitness due to genetic inbreeding but rather by increased mortality via demographic processes. In the short term, we suggest that conservation efforts should treat the Turkish subpopulations as a single management unit and aim to increase population size through effective protection, especially during the breeding season.     

Photoinhibition of Photosystem I damages both reaction centre proteins PSI-A and PSI-B and acceptor-side located small Photosystem I polypeptides

Photoinhibition of Photosystem I at chilling temperatures was investigated. Illumination of barley and cucumber leaves at 4°C induced a lowered Photosystem I activity. In barley, the reaction centre proteins PSI-A and PSI-B were both partially degraded as was the nuclear-encoded PSI-D polypeptide. Barley leaves infiltrated with KCN to increase oxidative stress, showed increased photoinhibition of Photosystem I, including reduced photochemical activity and marked degradation of several Photosystem I polypeptides. The most rapid and pronounced degradation was found in the PSI-D and PSI-E polypeptides exposed at the Photosystem I acceptor side. The PSI-A, -B, -C, -G, -H, -K and -L polypeptides were less extensively damaged. No damage of the lumenally oriented PSI-F and -N polypeptides was detected. The elevated photoinhibition of Photosystem I seen in KCN treated barley is most likely induced by a combination of increased active oxygen due to inhibited scavenging and increased accumulation of reducing power due to inhibition of the Calvin cycle. In barley, photo-inactivation of Photosystem I closely followed the degradation of PSI-A and PSI-B. Illumination of cucumber resulted in a pronounced loss of activity and appearance of specific PSI-A and PSI-B degradation products whereas the total PSI-A/B degradation was small. The PSI-A/B degradation identified in barley is interpreted to reflect a physiologically relevant process being part of a repair cycle, whereas the much smaller PSI-A/B degradation observed in cucumber is interpreted to represent an irreversible damage induced far below the temperature tolerance for cucumber.     

Nitric oxide‐mediated dispersal in single‐ and multi‐species biofilms of clinically and industrially relevant microorganisms

Strategies to induce biofilm dispersal are of interest due to their potential to prevent biofilm formation and biofilm‐related infections. Nitric oxide (NO), an important messenger molecule in biological systems, was previously identified as a signal for dispersal in biofilms of the model organism Pseudomonas aeruginosa. In the present study, the use of NO as an anti‐biofilm agent more broadly was assessed. Various NO donors, at concentrations estimated to generate NO levels in the picomolar and low nanomolar range, were tested on single‐species biofilms of relevant microorganisms and on multi‐species biofilms from water distribution and treatment systems. Nitric oxide‐induced dispersal was observed in all biofilms assessed, and the average reduction of total biofilm surface was 63%. Moreover, biofilms exposed to low doses of NO were more susceptible to antimicrobial treatments than untreated biofilms. For example, the efficacy of conventional chlorine treatments at removing multi‐species biofilms from water systems was increased by 20‐fold in biofilms treated with NO compared with untreated biofilms. These data suggest that combined treatments with NO may allow for novel and improved strategies to control biofilms and have widespread applications in many environmental, industrial and clinical settings.     

A G protein-coupled receptor-like module regulates cellulose synthase secretion from the endomembrane system in Arabidopsis

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NickFects,Phosphorylated Derivatives of Transportan 10 for Cellular Delivery of Oligonucleotides

Oligonucleotide-based gene regulation has a high potential in gene therapy, but the plasma membrane is impermeable for nucleic acid polymers and, consequently, an efficient and non-toxic transfection agent is needed for their delivery into the cell. In this study we present a novel series, NickFects, of chemically modified TP10 peptide-based delivery vectors used for the cellular delivery of single-stranded oligonucleotides. These carriers, obtained by replacement of Ile8 by threonine in stearyl-TP10 and by modifying of tyrosine and/or threonine, respectively, by phosphorylation formed 300–500 nm in size peptide:oligonucleotide nanocomplexes with negative surface charges. The highest splice-correcting effect was obtained when phosphorotiate 2′-O-methyl oligonucleotides were transduced into cells by NickFect1 (NF1) or NickFect2 (NF2). In addition, we also show how a small modification (one or two negative charges) in peptide sequence can affect its ability to deliver ONs into cells and increase their potency in the splicing redirection assay. Our studies demonstrate that NF1 and NF2 have higher transfection efficacy for oligonucleotides as compared to the most commonly used transfection agent Lipofectamine™ 2000 and lead to higher biological response in cells.