DAT, deacylating autotransporter toxin, from Bordetella parapertussis demyristoylates Gαi GTPases and contributes to cough.

The pathogenic bacteria Bordetella pertussis and Bordetella parapertussis cause pertussis (whooping cough) and pertussis-like disease, respectively, both of which are characterized by paroxysmal coughing. We previously reported that pertussis toxin (PTx), which inactivates heterotrimeric GTPases of the Gi family through ADP-ribosylation of their α subunits, causes coughing in combination with Vag8 and lipid A in B. pertussis infection. In contrast, the mechanism of cough induced by B. parapertussis, which produces Vag8 and lipopolysaccharide (LPS) containing lipid A, but not PTx, remained to be elucidated. Here, we show that a toxin we named deacylating autotransporter toxin (DAT) of B. parapertussis inactivates heterotrimeric Gi GTPases through demyristoylation of their α subunits and contributes to cough production along with Vag8 and LPS. These results indicate that DAT plays a role in B. parapertussis infection in place of PTx.

Cell Lysis Directed by SulA in Response to DNA Damage in Escherichia coli.

The SOS response is induced upon DNA damage and the inhibition of Z ring formation by the product of the sulA gene, which is one of the LexA-regulated genes, allows time for repair of damaged DNA. On the other hand, severely DNA-damaged cells are eliminated from cell populations. Overexpression of sulA leads to cell lysis, suggesting SulA eliminates cells with unrepaired damaged DNA. Transcriptome analysis revealed that overexpression of sulA leads to up-regulation of numerous genes, including soxS. Deletion of soxS markedly reduced the extent of cell lysis by sulA overexpression and soxS overexpression alone led to cell lysis. Further experiments on the SoxS regulon suggested that LpxC is a main player downstream from SoxS. These findings suggested the SulA-dependent cell lysis (SDCL) cascade as follows: SulA→SoxS→LpxC. Other tests showed that the SDCL cascade pathway does not overlap with the apoptosis-like and mazEF cell death pathways.

The direction of protein evolution is destined by the stability.

Protein evolution is potentially governed by protein stability. Here, we investigated the relationship between protein evolution and stability through the random mutational drift of a thermophilic bacterial protein, an esterase of Alicyclobacillus acidocaldarius (Aac-Est), at high and low temperatures. In the first random mutation of Aac-Est, few proteins exhibit increased activity at 65 °C, indicating that the wild-type (WT) Aac-Est is located on the peak of a mountain in a fitness landscape for activity at high temperature. To obtain higher active variants than those of WT, it must go down the mountain once and climb another, higher mountain. In the second and third generations from lower active templates, the evolvability (the proportion of variants with higher activity in all the variants obtained in a given generation than a parent protein) depended on the stability of the template proteins. Compared to WT, the stability-maintaining template could recover the activity more. Thus, a low-activity variant with high stability is able to drift vastly in sequence space and reach the foot of a higher mountain. Meanwhile, random mutations in stability-loss templates produced several variants with higher activity at 40 °C than those produced by WT, via cold adaptation. Our results indicate that maintaining protein stability enables the protein to search sequence space and evolve in the original environment, and proteins with lost stability use a cold adaptation path.

Normalization of sonographical multifocal nerve enlargements in a MADSAM patient following a good clinical response to intravenous immunoglobulin.

Focal nerve enlargements at sites of conduction blocks can be visualized sonographically in patients with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). However, little is known about association between nerve morphological changes and treatment responses. Here we present a 73-year-old female MADSAM patient whose sonographical multifocal nerve enlargements normalized following a good treatment response. She was admitted to our department with progressive asymmetrical muscle weakness and sensory disturbances for 6 months. Ultrasonography revealed multifocal nerve enlargements at sites of electrophysiological demyelination. Intravenous immunoglobulin improved her symptoms and electrophysiological abnormalities. Six months later, ultrasonography revealed normalization of multifocal nerve enlargements. Contrary to our observations, one previous report described a MADSAM patient with persistent nerve enlargements at the sites of resolved conduction blocks. In this earlier patient, however, the time from onset to remission was approximately 30 months. Morphological changes of nerve enlargements in MADSAM may vary with treatment response.