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SUMMARY
The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood-group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive but binding is restored by pH neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions; changes during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA’s extraordinary reversible acid-responsiveness enables tight mucosal bacterial adherence while at the same time allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutations and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, and BabA’s adaptive evolution contributes importantly to H. pylori persistence and to overt gastric disease.
Contamination of
toxic spore-forming bacteria is problematic since
spores can survive a plethora of disinfection chemicals and it is
hard to rapidly detect if the disinfection chemical has inactivated
the spores. Thus, robust decontamination strategies and reliable detection
methods to identify dead from viable spores are critical. In this
work, we investigate the chemical changes of
Bacillus
thuringiensis
spores treated with sporicidal agents
such as chlorine dioxide, peracetic acid, and sodium hypochlorite
using laser tweezers Raman spectroscopy. We also image treated spores
using SEM and TEM to verify if we can correlate structural changes
in the spores with changes to their Raman spectra. We found that over
30 min, chlorine dioxide did not change the Raman spectrum or the
spore structure, peracetic acid showed a time-dependent decrease in
the characteristic DNA/DPA peaks and ∼20% of the spores were
degraded and collapsed, and spores treated with sodium hypochlorite
showed an abrupt drop in DNA and DPA peaks within 20 min and some
structural damage to the exosporium. Structural changes appeared in
spores after 10 min, compared to the inactivation time of the spores,
which is less than a minute. We conclude that vibrational spectroscopy
provides powerful means to detect changes in spores but it might be
problematic to identify if spores are live or dead after a decontamination
procedure.
Changes in cell morphology require coordination of plasma membrane turnover and cytoskeleton dynamics, processes that are regulated by Rho GTPases. Here, we describe how a direct interaction between the Rho GTPase Cdc42 and the GTPase-activating protein (GAP) GRAF1 (also known as ARHGAP26), facilitates rapid cell surface turnover at the leading edge. Both Cdc42 and GRAF1 were required for fluid-phase uptake and regulated the generation of transient GRAF1-coated endocytic carriers, which were distinct from clathrin-coated vesicles. GRAF1 was found to transiently assemble at discrete Cdc42-enriched punctae at the plasma membrane, resulting in a corresponding decrease in the microdomain association of Cdc42. However, Cdc42 captured in its active state was, through a GAP-domain-mediated interaction, localised together with GRAF1 on accumulated internal structures derived from the cell surface. Correlative fluorescence and electron tomography microscopy revealed that these structures were clusters of small membrane carriers with defective endosomal processing. We conclude that a transient interaction between Cdc42 and GRAF1 drives endocytic turnover and controls the transition essential for endosomal maturation of plasma membrane internalised by this mechanism.
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