Patrick Becker, Fiona B. Naughton, Deborah H. Brotherton, Raul Pacheco-Gomez, Oliver Beckstein, Alexander D. Cameron

The bile acid sodium symporter (BASS) family transports a wide array of molecules across membranes, including bile acids in humans, and small metabolites in plants. These transporters, many of which are sodium-coupled, have been shown to use an elevator mechanism of transport, but exactly how substrate binding is coupled to sodium ion binding and transport is not clear. Here, we solve the crystal structure at 2.3 Å of a transporter from Neisseria meningitidis (ASBT_NM) in complex with pantoate, a potential substrate of ASBT_NM.. Comparison of structures in the presence and absence of pantoate demonstrates that pantoate elicits a conformational change in one of the cross-over helices. This modifies the interface between the two domains that move relative to one another to elicit the elevator mechanism. These results have implications, not only for ASBT_NM but for the BASS family as a whole and indeed other transporters that work through the elevator mechanism.

eLife. November 2023

Holly Acford-Palmer, Monica Campos, Janvier Bandibabone, Sévérin N’Do, Chimanuka Bantuzeko, Bertin Zawadi, Thomas Walker, Jody E. Phelan, Louisa A. Messenger, Taane G. Clark & Susana Campino

Vector control strategies have been successful in reducing the number of malaria cases and deaths globally, but the spread of insecticide resistance represents a significant threat to disease control. To support the continuous efficacy of vector control strategies, it is essential to monitor insecticide resistance using molecular surveillance tools. In this study, we developed an amplicon sequencing (“Amp-seq”) approach targeting An. funestus, and using multiplex PCR, dual index barcoding, and next-generation sequencing for high throughput and low-cost applications. Overall, our panel represents an extendable and much-needed method for the molecular surveillance of insecticide resistance in An. funestus populations.

Scientific Reports. October 2023

Yiying Yang, Haoxiang Chen, Robin A. Corey, Violette Morales, Yves Quentin, Carine Froment, Anne Caumont-Sarcos, Cécile Albenne, Odile Burlet-Schiltz, David Ranava, Phillip J. Stansfeld, Julien Marcoux, Raffaele Ieva

Insertion of lipopolysaccharide (LPS) into the bacterial outer membrane (OM) is mediated by a druggable OM translocon consisting of a β-barrel membrane protein, LptD, and a lipoprotein, LptE. The β-barrel assembly machinery (BAM) assembles LptD together with LptE at the OM. In the enterobacterium Escherichia coli, formation of two native disulfide bonds in LptD controls translocon activation. Here we report the discovery of LptM (formerly YifL), a lipoprotein conserved in Enterobacteriaceae, that assembles together with LptD and LptE at the BAM complex.. Our results suggest that, by mimicking LPS binding, LptM facilitates oxidative maturation of LptD, thereby activating the LPS translocon.

Nature Communications. October 2023

Chan, Y. L. Elaine, Irvine, Michael A., Prystajecky, Natalie, Sbihi, Hind, Marsha, Taylor, Joffres , Yayuk, Schertzer, Andrea, Rose, Caren, Dyson, Louise, Hill, Edward M., Tildesley, Michael J., Tyson, John R., Hoang, Linda M. N. and Galanis, Eleni

In British Columbia, Canada, initial growth of the SARS-CoV-2 Delta variant was slower than that reported in other jurisdictions. We describe the growth of Delta variant cases in British Columbia during March1 – June 20 2021, and apply retrospective counterfactual modelling to examine factors for the initially low COVID-19 case rate after Delta introduction, such as vaccination coverage and nonpharmaceutical interventions. Grwth of COVID-19 cases in the first 3 months after Delta emergence was likely limited in British Columbia because additional nonpharmaceutical interventions were implemented.

Emerging Infectious Diseases.October 2023

Aina Mercant Osuna, Alexandra Gidley, Marie Paul Audrey Mayi, Roland Bamou, Vishaal Dhokiya, Christophe Antonio-Nkondjio, Claire Louise Jeffries, Thomas Walker

The endosymbiotic bacterium Wolbachia infects numerous species of insects and Wolbachia transinfection of Aedes mosquito species is now being used for biocontrol programs as Wolbachia strains can both inhibit arboviruses and invade wild mosquito populations. The discovery of novel, resident Wolbachia strains in mosquito species warrants further investigation as potential candidate strains for biocontrol strategies. We obtained mosquito specimens from diverse Culicine mosquitoes from Cameroon including ecologically diverse locations in the Central and West Regions. Wolbachia prevalence rates were assessed in addition to the environmentally acquired bacterial species Asaia in major Culicine genera Our study provides further evidence that Wolbachia is widespread within wild mosquito populations of diverse Culicine species and provides further candidate strains that could be investigated as future options for Wolbachia-based biocontrol to inhibit arbovirus transmission.

Wellcome Open Research. September 2023

Arturo Torres Ortiz, Michelle Kendall, Nathaniel Storey, James Hatcher, Helen Dunn, Sunando Roy, Rachel Williams, Charlotte Williams, Richard A Goldstein, Xavier Didelot, Kathryn Harris, Judith Breuer, Louis Grandjean

Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. We hypothesized that including within-sample variation in a phylogenetic model would help to identify who infected whom in instances in which this was previously impossible. Using whole-genome sequences from SARS-CoV-2 multi-institutional outbreaks as an example, we show how within-sample diversity is partially maintained among repeated serial samples from the same host, it can transmitted between those cases with known epidemiological links, and how this improves phylogenetic inference and our understanding of who infected whom. Our technique is applicable to other infectious diseases and has immediate clinical utility in infection prevention and control.

eLife. September 2023