pressure and have acquired resistance to fewer antibiotics. Both types of MRSA maintain chromosomal mutations that confer resistance to some therapies; these mutations are selected for and maintained in healthcare environments. HA-MRSA strains cause disease in immunocompromised individuals and are rarely isolated from patients with MRSA infections that are not linked to healthcare settings. In contrast, CA-MRSA strains typically cause infection in immunocompetent and otherwise healthy people. The mechanisms underlying this difference are still unclear and are likely multifactorial. Some evidence suggests that the acquisition of multiple antibiotic-resistance determinants by HA-MRSA strains actually reduces the “fitness” of the organism, which makes them unable to colonize and/or infect otherwise healthy people.


Protein toxins in bacteria are often associated with mobile genetic elements such as phages and plasmid DNA. For this reason many toxin genes have spread between species by horizontal gene transfer. Production of active toxin sometimes requires the presence of accessory proteins for posttranslational modification and/or export. Thus the detection of a toxin gene is not necessarily predictive of virulence. These toxins may be grouped into two broad categories, structural and enzymatic. Structural toxins produce an effect solely through interactions with the target cell while enzymatic toxins catalyze a specific reaction that has an effect on the cell.

Acquisition of Shiga toxin-encoding bacteriophage. The emergence of Shiga toxin-producing E. coli strains in the early 1980s provides a clear example of how common bacteria may acquire bacteriophages that encode virulence traits such as bacterial toxin genes. This horizontal transfer of genetic material among bacteria via phage infection can result in the rapid evolution of new pathogens. The E. coli serotype O157 cited above was previously unknown as a pathogen in humans; however, the incorporation of genes homologous to those that encode Shiga toxin in the related agent of bacillary dysentery, Shigella dysenteriae type 1, generated a strain that produces hemorrhagic colitis and the life-threatening hemolytic uremic syndrome in humans.

Shiga toxins are AB5 toxins (one polypeptide chain that has enzymatic activity and 5 cell-binding subunits) that are among the most potent toxins known. They kill sensitive cells by shutting down protein synthesis in a manner identical to that of ricin. Indeed, Shiga toxins, like ricin, are classified as SAs. In addition to E. coli O157, several other serotypes of E. coli and some related species including Shigella sonnei, Aeromonas hydrophila, and Enterobacter cloacae have been described that encode related Shiga-type toxins within lysogenic (chromosomally-integrated) bacteriophages and cause disease in humans. Bacteriophages are thought to be the most plentiful infectious forms on Earth.

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