Phase-variable bacterial loci: how bacteria gamble to maximise fitness in changing environments

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Phillips, Zachary N
Tram, Greg
Seib, Kate L
Atack, John M
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2019
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Abstract

Phase-variation of genes is defined as the rapid and reversible switching of expression — either ON-OFF switching or the expression of multiple allelic variants. Switching of expression can be achieved by a number of different mechanisms. Phase-variable genes typically encode bacterial surface structures, such as adhesins, pili, and lipooligosaccharide, and provide an extra contingency strategy in small-genome pathogens that may lack the plethora of ‘sense-and-respond’ gene regulation systems found in other organisms. Many bacterial pathogens also encode phase-variable DNA methyltransferases that control the expression of multiple genes in systems called phasevarions (phase-variable regulons). The presence of phase-variable genes allows a population of bacteria to generate a number of phenotypic variants, some of which may be better suited to either colonising certain host niches, surviving a particular environmental condition and/or evading an immune response. The presence of phase-variable genes complicates the determination of an organism’s stably expressed antigenic repertoire; many phase-variable genes are highly immunogenic, and so would be ideal vaccine candidates, but unstable expression due to phase-variation may allow vaccine escape. This review will summarise our current understanding of phase-variable genes that switch expression by a variety of mechanisms, and describe their role in disease and pathobiology.

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Biochemical Society Transactions

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47

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4

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© 2019 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Biochemistry and cell biology

Medical biochemistry and metabolomics

Science & Technology

Life Sciences & Biomedicine

Biochemistry & Molecular Biology

PILIN-ANTIGENIC-VARIATION

NONTYPABLE HAEMOPHILUS-INFLUENZAE

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Phillips, ZN; Tram, G; Seib, KL; Atack, JM, Phase-variable bacterial loci: how bacteria gamble to maximise fitness in changing environments, Biochemical Society Transactions, 2019, 47 (4), pp. 1131-1141

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