Bacteriocins are toxins deployed by bacteria to kill their competitors. Here, I reflect on my laboratory’s work on protein bacteriocins and their immunity proteins from Gram-negative bacteria. We unco...

PhD Project - Forged by Iron: Synthetic protein binders to decode bacterial iron transport mechanisms at Newcastle University, listed on FindAPhD.com

Two-partner secretion system transporter proteins (TpsB) are widely conserved across Gram-negative pathogens. TpsB family proteins secrete exoprotein virulence factors that perform a myriad of functions such as adhesion and immune modulation. Despite their incredible importance in bacterial infectious disease, TpsB inhibitors have not yet been discovered. Here, we describe a potent inhibitor of FhaC, a TpsB protein produced by Bordetella spp . FhaC secretes the exoprotein FhaB that is essential for the establishment of whooping cough. We designed a peptide called P1 that we predicted would prevent substrate binding and lock FhaC in a secretion-inactive state. Simulations and biochemical assays supported our hypothesis and identified interactions important for P1 binding to FhaC. Strikingly, we observed that the peptide strongly inhibited FhaB secretion from clinical isolates and broadly reduced correlates of virulence. Together, this work provides a strong case for further development of a novel class of anti-TpsB anti-virulence compounds. ### Competing Interest Statement The authors have declared no competing interest. National Institute of Allergy and Infectious Diseases, R21AI180112

The UK left in December 2020 as part of the post-Brexit trade deal with the EU negotiated by Boris Johnson.

An analysis of AlphaFold protein structure predictions shows that while in many cases the predictions are highly accurate, there are also many instances where the predicted structures or parts of pred...

AMPA receptors (AMPARs) are multimodal transducers of glutamatergic signals throughout the brain. Their diversity is exemplified in the cerebellum; at afferent synapses, AMPARs mediate high-frequency ...

Multi-scale molecular dynamics simulations reveal that polymyxins form polymyxin-protein aggregates upon associating with the E. coli outer membrane thereby reducing lateral mobility of outer membrane...

In E.coli, three of the four Type VII ABC transporter systems have been structurally characterized. This study solves cryo-EM structures of the fourth Type VII ABC system, YbbAP-TesA, and suggests tha...

Screening of 1,076 compounds reveals 168 chemical pollutants with inhibitory effects on gut bacteria and genetic screens indicate commonality between pollutant and antibiotic resistance.

Natural genetic transformation is a conserved mechanism of bacterial horizontal gene transfer, which is directed entirely by the recipient cell and...

Fusidic acid (FA) is one of few remaining antibiotics active against Methicillin-resistant Staphylococcus aureus. FusB confers resistance to FA by ...

Nature Communications - The asymmetric distribution of lipopolysaccharide (LPS) on the surface of the bacterial outer membrane is essential and crucial for antibiotic resistance. Here, authors...

Human methionine synthase (MTR) is an essential enzyme of one carbon metabolism. Consisting of a catalytic N-half and a cobalamin binding C-half, MTR utilises this intricate organometallic cofactor in...