Haemophilus influenzae : Genetic Variability and Natural Selection To Identify Virulence Factors

Abstract

The evolutionary processes of natural selection govern the nucleotide sequences of bacterial genes such that during replication over many generations, bacterial virulence factor genes change and their products become diverse. This diversity, which both facilitates and reflects an organism's ability to survive in a variety of ecologic niches and under different environmental conditions, occurs through two general strategies—variation in gene expression, which is driven by mechanisms governing gene transcription or translation, and variation in gene content, which is driven by either vertical or horizontal evolution. In this regard, vertical evolution refers to the passage of genetic material from parent to offspring through cell division, with its attendant mutations resulting from mistakes in replication such as point mutations, gene inversions, or spontaneous deletions. Horizontal evolution in bacterial cells occurs by the acquisition of new genetic material from transformation of native DNA, transduction by phages, or conjugation by plasmids; this new genetic material is then passed on to subsequent generations through vertical evolution. Until recently, bacterial pathogens were characterized solely by their phenotypic characteristics, which describe only gross strain-to-strain differences. While extremely useful, these techniques are limited in their ability to identify unique members of widely variable bacterial populations. Recent advances in bacterial genomics, furthered by the availability of complete genomic sequences from a growing number of organisms, suggest that some “clonal” designations may be misguided, given the high level of genetic diversity of bacterial strains from the same species. For example, sequence comparisons have shown up to 25% differences in gene content among strains of Neisseria meningitidis, Helicobacter pylori, and Escherichia coli (5). While individual fitness characteristics of bacteria foster the survival of individual organisms, the population dynamics of bacteria encompass fitness characteristics that foster the survival of the group. As in all populations, not every member of a bacterial population needs to succeed in all possible environments; rather, the sum of the specialized fitnesses of individual bacteria ensures the survival of the population in variable environments. Thus, gene products required for bacterial survival in one environmental niche may not be required in another niche. Over time and under the influence of natural selection, the gene contents of organisms from the same species living in different niches will be altered to reflect the necessity for certain genes and the dispensability of others. Bacterial factors that are highly diverse are most susceptible to this process of selection. In this paper we describe how the results of evolutionary processes, as reflected by bacterial population characteristics, may be used to identify potential bacterial virulence factors. We use Haemophilus influenzae, whose known virulence factors are highly variable, as an example.