Regulation of bacterial virulence. During their transition through the mammalian gut, enteric bacteria experience many harsh environmental conditions, having to cope with limited nutrients, low oxygen tensions and the presence of toxic molecules. Thus, to survive and cause disease, enteric pathogens must sense their environment and adapt by altering their patterns of gene expression. This is largely achieved by controlling transcription initiation and in many cases involves the interplay of several global transcription factors at promoter regions. Doug Browning’s research examines how global transcription factors (e.g. CRP, FNR, AggR and NarL) and protein factors which fold the bacterial chromosome (e.g. IHF, Fis and HNS) can coordinate genome wide gene expression in pathogens such as enteroaggregative E. coli (EAEC), Shigella flexneri and Salmonella enterica serovar Typhimurium.
Insertion of β-barrel membrane proteins into the outer membranes of bacteria. Gram-negative bacteria have an outer membrane that functions as a barrier to protect the bacterium from toxic compounds such as antibiotics and detergents. It is composed of phospholipids, lipopolysaccharide (LPS) and two major classes of proteins, lipoproteins and integral β-barrel outer membrane proteins (OMPs). Insertion of OMPs in E. coli is an essential process and is carried out by the BAM complex (β-barrel assembly machinery). In E. coli this multi-protein complex consists of the OMP BamA and four accessory lipoproteins (BamB, BamC, BamD and BamE). Doug Browning’s research examines how the BAM complex orchestrates the folding and insertion of OMPs into the outer membrane of E. coli and how this machinery differs in other important Gram-negative bacteria, such as Haemophilus influenzae, Pseudomonas aeruginosa and Neisseria meningitidis.
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