The reaction-diffusion basis of animated patterns in eukaryotic flagella.

The flagellar beat of bull spermatozoa and C. Reinhardtii are modelled by a minimal, geometrically exact, reaction-diffusion system. Spatio-temporal animated patterns describe flagellar waves, analogous to chemical-patterns from classical reaction-diffusion systems, with sliding-controlled molecular motor reaction-kinetics. The reaction-diffusion system is derived from first principles as a consequence of the high-internal dissipation by the flagellum relative to the external hydrodynamic dissipation. Quantitative comparison with nonlinear, large-amplitude simulations shows that animated reaction-diffusion patterns account for the experimental beating of both bull sperm and C. Reinhardtii. Our results suggest that a unified mechanism may exist for motors controlled by sliding, without requiring curvature-sensing, and uninfluenced by hydrodynamics. High-internal dissipation instigates autonomous travelling waves independently of the external fluid, enabling progressive swimming, otherwise not possible, in low viscosity environments, potentially critical for external fertilizers and aquatic microorganisms. The reaction-diffusion system may prove a powerful tool for studying pattern formation of movement on animated structures.

Targetable nano-delivery vehicles to deliver anti-bacterial small acid-soluble spore protein (SASP) genes.

Interest in phage-based therapeutics is increasing, at least in part due to the need for new treatment options for infections caused by antibiotic-resistant bacteria. It is possible to use wild-type (WT) phages to treat bacterial infections, but it is also possible to modify WT phages to generate therapeutics with improved features. Here, we will discuss features of Phico Therapeutics' SASPject technology, which modifies phages for use as targetable nano-delivery vehicles (NDV), to introduce antibacterial Small Acid Soluble Spore Protein (SASP) genes into specific target bacteria.

Engineered Bacteriophage as a Delivery Vehicle for Antibacterial Protein, SASP.

The difficulties in developing novel classes of antibacterials is leading to a resurgence of interest in bacteriophages as therapeutic agents, and in particular engineered phages that can be optimally designed. Here, pre-clinical microbiology assessment is presented of a Staphylococcus aureus phage engineered to deliver a gene encoding an antibacterial small acid soluble spore protein (SASP) and further, rendered non-lytic to give product SASPject PT1.2. PT1.2 has been developed initially for nasal decolonisation of S. aureus, including methicillin-resistant S. aureus. Time-kill curve assays were conducted with PT1.2 against a range of staphylococcal species, and serial passaging experiments were conducted to investigate the potential for resistance to develop. SASPject PT1.2 demonstrates activity against 100% of 225 geographically diverse S. aureus isolates, exquisite specificity for S. aureus, and a rapid speed of kill. The kinetics of S. aureus/PT1.2 interaction is examined together with demonstrating that PT1.2 activity is unaffected by the presence of human serum albumin. SASPject PT1.2 shows a low propensity for resistance to develop with no consistent shift in sensitivity in S. aureus cells passaged for up to 42 days. SASPject PT1.2 shows promise as a novel first-in-class antibacterial agent and demonstrates potential for the SASPject platform.

Three novel bacteriophages isolated from the East African Rift Valley soda lakes.

BACKGROUND: Soda lakes are unique environments in terms of their physical characteristics and the biology they harbour. Although well studied with respect to their microbial composition, their viral compositions have not, and consequently few bacteriophages that infect bacteria from haloalkaline environments have been described. METHODS: Bacteria were isolated from sediment samples of lakes Magadi and Shala. Three phages were isolated on two different Bacillus species and one Paracoccus species using agar overlays. The growth characteristics of each phage in its host was investigated and the genome sequences determined and analysed by comparison with known phages. RESULTS: Phage Shbh1 belongs to the family Myoviridae while Mgbh1 and Shpa belong to the Siphoviridae family. Tetranucleotide usage frequencies and G + C content suggests that Shbh1 and Mgbh1 do not regularly infect, and have therefore not evolved with, the hosts they were isolated on here. Shbh1 was shown capable of infecting two different Bacillus species from the two different lakes demonstrating its potential broad-host range. Comparative analysis of their genome sequence with known phages revealed that, although novel, Shbh1 does share substantial amino acid similarity with previously described Bacillus infecting phages (Grass, phiNIT1 and phiAGATE) and belongs to the Bastille group, while Mgbh1 and Shpa are highly novel. CONCLUSION: The addition of these phages to current databases should help with metagenome/metavirome annotation efforts. We describe a highly novel Paracoccus infecting virus (Shpa) which together with NgoΦ6 and vB_PmaS_IMEP1 is one of only three phages known to infect Paracoccus species but does not show similarity to these phages.