Bacterial pathogens face stringent challenges to their survival because of the many unpredictable, often precipitate, and dynamic changes that occur in the host environment or in the process of transmission from one host to another. Bacterial adaptation to their hosts involves either a mechanism for sensing and responding to external changes or the selection of variants that arise through mutation. Here we review how bacterial pathogens exploit localized hypermutation, through polymerase slippage of simple sequence repeats (SSRs), to generate phenotypic variation and enhanced fitness. These SSRs are located within the reading frame or in the promoter of a subset of genes, often termed contingency loci, whose functions are usually involved in direct interactions with host structures.

The nucleotide sequences of the large open reading frame (ORF) from segment A of three European strains of infectious bursal disease virus (IBDV) have been determined using cDNA clones. This ORF of 3036 nucleotides encodes the virion proteins as a polyprotein in the following order: VP2, VP4, VP3. The nucleotide sequences determined have been compared to each other and to the published sequence of an Australian strain. The four strains are closely related, the greatest difference between two strains being 7.7% at the nucleotide level and 2.7% at the amino acid level. Comparisons show that there is a tight cluster of amino acid changes in the virion protein VP2. This variable region corresponded to the region where binding of a neutralizing monoclonal antibody has previously been mapped. A region in the centre of the segment, corresponding to the N terminal of VP4, was found to be completely conserved. Amino acid changes were spread fairly evenly through VP3 and there was no indication of a variable region as found in VP2.

Haemophilus influenzae is an obligate commensal of the upper respiratory tract of humans that uses simple repeats (microsatellites) to alter gene expression. The mod gene of H. influenzae strain Rd has homology to DNA methyltransferases of type III restriction/modification systems and has 40 tetranucleotide (5′‐AGTC) repeats within its open reading frame. This gene was found in 21 out of 23 genetically distinct H. influenzae strains, and in 13 of these strains the locus contained repeats. H. influenzae strains were constructed in which a lacZ reporter was fused to a chromosomal copy of mod downstream of the repeats. Phase variation occurred at a high frequency in strains with the wild‐type number of repeats. Mutation rates were derived for similarly engineered strains, containing different numbers of repeats. Rates increased linearly with tract length over the range 17–38 repeat units. The majority of tract alterations were insertions or deletions of one repeat unit with a 2:1 bias towards contractions of the tract. These results demonstrate the number of repeats to be an important determinant of phase variation rate in H. influenzae for a gene containing a microsatellite.

Phase variation (PV) of surface molecules and other phenotypes is a major adaptive strategy of pathogenic and commensal bacteria. Phase variants are