No abstract

Bacterial toxins damage the host at the site of bacterial infection or distanced from the site of infections. Bacterial toxins can be single proteins or organized as oligomeric protein complexes and are organized with distinct AB structure-function properties. The A domain encodes a catalytic activity; ADP-ribosylation of host proteins is the earliest post-translational modification determine to be performed by bacterial toxin, and now include glucosylation and proteolysis among other s. Bacterial toxins also catalyze the non-covalent modification of host protein function or can modify host cell properties through direct protein-protein interactions. The B domain includes two functional domains: a receptor-binding domain, which defines the tropism of a toxin for a cell and a translocation domain that delivers A domain across a lipid bilayer, either on the plasma membrane or the endosome. Bacterial toxins are often characterized based upon the section mechanism that delivers the toxin out of the bacterium, termed type I–VII. This review will overview the major families of bacterial toxins and will also describe the specific structure-function properties of the botulinum neurotoxins.

Botulinum toxins (BoNT) are zinc proteases (serotypes A-G) which cause flaccid paralysis through the cleavage of SNARE proteins within motor neurons. BoNT/A was originally organized into two subtypes: BoNT/A1 and BoNT/A2, which are ~ 95 % homologous and possess similar catalytic activities. Subsequently, two additional subtypes were identified; BoNT/A3 (Loch Maree), and BoNT/A4 (657Ba), which have 81 and 88% homology with BoNT/A1, respectively. Alignment studies predicted that BoNT/A3 and BoNT/A4 were sufficiently different to BoNT/A1 to affect SNAP25 binding and cleavage. Recombinant Light Chain (LC) of BoNT/A3 (LC/A3) and BoNT/A4 (LC/A4) were subjected to biochemical analysis. LC/A3 cleaved SNAP25 at 50% the rate of LC/A1, but cleaved SNAPtide® at a faster rate than LC/A1, while LC/A4 cleaved SNAP25 and SNAPtide® at slower rates than LC/A1. LC/A3 and LC/A4 had similar Kms for SNAP25 relative to LC/A1, while the kcat for LC/A4 was 10- fold slower than LC/A1, suggesting a defect in substrate cleavage. Neither LC/A3 nor LC/A4 possessed autocatalytic activity, a property of LC/A1 and LC/A2. Thus, the four subtypes of BoNT/A bind SNAP25 with similar affinity but have different catalytic capacities for SNAP25 cleavage, SNAPtide® cleavage, and autocatalysis. The catalytic properties identified among the subtypes of LC/A may influence strategies for the development of small molecule- or peptide- inhibitors as therapies against botulism.

In 2001, West Nile virus (WNV) was identified among dead American crows and bluejays in five counties in southeastern Wisconsin. In response to the introduction of WNV, a pilot mosquito surveillance program was initiated in these five southeastern Wisconsin counties during the summer of 2002. Forty sites were selected for surveillance one night each week during a 17-week period. Mosquitoes were collected in carbon dioxide-baited light traps and gravid traps. During the study period 31,419 mosquitoes were collected, identified to species level and pooled into groups of up to 50 mosquitoes of like species from each collection site. Twenty-five different mosquito species were identified with the common pest mosquitoes, Aedes vexans and Ochlerotatus trivittatus, being the most abundant. Seventeen of the 25 mosquito species found in southeastern Wisconsin have previously been shown to be carriers of WNV in other parts of the U.S. Only 2/1,592 (0.126%) mosquito pools from Wisconsin were positive for WNV by cell culture and reverse transcription polymerase chain reaction (RT-PCR). Active mosquito surveillance is useful for identifying potential mosquito vectors of arboviruses in defined geographic areas, and to monitor population densities of those vectors. This information coupled with infection rate data can help guide public health policies related to vector control, and may help reduce the impact on human, veterinary and bird mortality.