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Chapter 10 : The Evolution of Bacterial Toxins
Category: Bacterial Pathogenesis; Microbial Genetics and Molecular Biology
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The prevailing paradigm of bacterial evolution is clonal descent with periodic modification, punctuated with discrete occurrences of horizontal genetic transmission. This latter phenomenon, termed "mosaicism," is reported with increasing frequency among bacterial toxins. Toxins are generally thought to execute one of two principal pathogenic functions: host avoidance and host damage. However, a prominent theme of bacterial toxin research in the last decade is the identification of multiple patho-genetic functions for bacterial toxins. In terms of evolution, it may be most efficient to adopt virulence factors from another pathogenic organism or to embue an existing one with additional functions. It should be noted that, of the extant STa molecules, none is clearly primative in the evolutionary sense, yet it is interesting to note that, like guanylin, EAST-1 contains four cysteine residues, rather than the six present in STaH and STaP. The typical RTX toxin is encoded by a four-gene operon comprising, in order, the modifying enzyme, the toxin structural gene, and the two components of the secretion system. The accessory genes are highly conserved among the RTX toxins, whereas there is substantial diversity among the toxin structural genes. The fundamental mechanisms of bacterial evolution operate on toxin genes as they do on all genetic loci.
(A) Schematic representation of the mosaic structures of alleles representative of the major allelic groups of lktA leukotoxin in Pasteurella. The different colors indicate sequence identity and the likely origins of the recombinant segments. The number of sites different from those in the corresponding region of the likely donor allele(s) and the degree of divergence are indicated below certain recombinant segments; all other segments exhibited 100% sequence identity to the corresponding regions of the donor alleles. Numbers above the proposed recombination sites indicate the position of the last nucleotide at the downstream end of the recombination segment. (B) Proposed sequence of recombination events in the evolution of lktA to the formation of the lktA8- and lktA10-type alleles (see panel A) in the ovine-specific lineages of Pasteurella leukotoxins and the bovine-specific allele lktA2. This analysis suggests not only substantial mosaicism of the toxins, but also host-switching phenomena from ovine- to bovine- and back to ovine-specific alleles. Reprinted from reference 32 with permission.
Phylogenic tree of the clostridial neurotoxins drawn with the Phylip program. Reprinted from reference 133 with permission.
Phylogenetic trees of the SPATE proteins generated using ClustalX analysis of amino acid sequences from full-length SPATE passenger domains (A) or the N-terminal one-third (B) corresponding to amino acid 242 of the Pet toxin. Substrates subject to proteolysis are indicated in panel B. Reprinted from reference 39 with permission of the publisher.
The STa family of toxins
Summary of SPATE functions