Staunton, K. | bioRxiv Science

bioRxiv2020

Structure-function analyses of dual-BON domain protein DolP identifies phospholipid binding as a new mechanism for protein localisation

The Gram-negative outer membrane envelops the bacterium and functions as a permeability barrier against antibiotics, detergents and environmental stresses. Some virulence factors serve to maintain the integrity of the outer membrane, including DolP (formerly YraP) a protein of unresolved structure and function. Here we reveal DolP is a lipoprotein functionally conserved among Gram-negative bacteria and that loss of DolP increases membrane fluidity. We present the NMR solution structure for DolP, which is composed of two BON domains that form an interconnected opposing pair. The C-terminal BON domain binds to anionic phospholipids through an extensive membrane:protein interface providing evidence of subcellular localization of these phospholipids within the outer membrane. This interaction is essential for DolP function and is required for sub-cellular localization of the protein to the cell division site. The structure of DolP provides a new target for developing therapies that disrupt the integrity of the bacterial cell envelope.

biochemistry↗

bioRxiv2020

Modelling the Wolbachia Incompatible Insect Technique: strategies for effective mosquito population elimination

The Wolbachia Incompatible Insect Technique (IIT) shows promise as a method for eliminating invasive mosquitoes such as Aedes aegypti (Linnaeus)(Diptera: Culicidae) and reducing the incidence of vector-borne diseases such as dengue, chikungunya and Zika. Successful implementation of this biological control strategy relies on high-fidelity separation of male from female insects in mass production systems for inundative release into landscapes. Processes for sex-separating mosquitoes are typically error prone, laborious and IIT programs run the risk of releasing Wolbachia infected females and replacing wild mosquito populations. We introduce a simple Markov Population Process (MPP) model for studying mosquito populations subjected to a Wolbachia-IIT program which exhibit an unstable equilibrium threshold. The model is used to study, in silico, scenarios that are likely to yield a successful elimination result. Our results suggest that elimination is best achieved by releasing males at rates that adapt to the ever-decreasing wild population, thus reducing the risk of releasing Wolbachia-infected females while reducing costs. While very high-fidelity sex-separation is required to avoid establishment, release programs tend to be robust to the release of a small number of Wolbachia-infected females. These findings will inform and enhance the next generation of Wolbachia-IIT control strategies that are already showing great promise in field trials.

zoology↗