Co-evolution between host and pathogen is, in principle, a powerful determinant of the biology and genetics of infection and disease. Yet co-evolution has proven difficult to demonstrate rigorously in practice, and co-evolutionary thinking is only just beginning to inform medical or veterinary research in any meaningful way, even though it can have a major influence on how genetic variation in biomedically important traits is interpreted. Improving our understanding of the biomedical significance of co-evolution will require changing the way in which we look for it, complementing the phenomenological approach traditionally favored by evolutionary biologists with the exploitation of the extensive data becoming available on the molecular biology and molecular genetics of host-pathogen interactions.

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Biological and biomedical implications of the co-evolution of pathogens and their hosts

Interactions between bacteria and the viruses that infect them (i.e., phages) have profound effects on biological processes, but despite their importance, little is known on the general structure of infection and resistance between most phages and bacteria. For example, are bacteria–phage communities characterized by complex patterns of overlapping exploitation networks, do they conform to a more ordered general pattern across all communities, or are they idiosyncratic and hard to predict from one ecosystem to the next? To answer these questions, we collect and present a detailed metaanalysis of 38 laboratory-verified studies of host–phage interactions representing almost 12,000 distinct experimental infection assays across a broad spectrum of taxa, habitat, and mode of selection. In so doing, we present evidence that currently available host–phage infection networks are statistically different from random networks and that they possess a characteristic nested structure. This nested structure is typified by the finding that hard to infect bacteria are infected by generalist phages (and not specialist phages) and that easy to infect bacteria are infected by generalist and specialist phages. Moreover, we find that currently available host–phage infection networks do not typically possess a modular structure. We explore possible underlying mechanisms and significance of the observed nested host–phage interaction structure. In addition, given that most of the available host–phage infection networks examined here are composed of taxa separated by short phylogenetic distances, we propose that the lack of modularity is a scale-dependent effect, and then, we describe experimental studies to test whether modular patterns exist at macroevolutionary scales.

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Statistical structure of host-phage interactions.

Among a large collection of hemolysis-negative mutants obtained by mutagenesis of the Hly plasmid pHly152 with Tn5, we have isolated two classes of mutants which are defective in the transport of hemolysin across the outer membrane. The two cistrons (hylBa and hlyBb) which are affected in these mutants are located adjacent to each other on the hly determinant but are transcribed from different promoters. Recombinant plasmids were constructed which carry the two functions as combined or separated cistrons. These were shown to complement the two types of transport mutants. Studies on the compartmentation of hemolysin in these two classes of mutants indicate that most hemolysin (greater than 70%) in hlyBa mutants is located in the periplasmic space, whereas in hlyBb mutants a larger portion of hemolysin is associated with the outer membrane fraction. The phenotypic appearance of colonies from hlyBb mutants is that of beta-hemolytic Escherichia coli strains, indicating that a substantial portion of hemolysin has already reached the outside of the outer membrane without being released into the medium. Release was achieved readily when hlyBb mutants were complemented with a recombinant plasmid carrying hlyBb.

Transport of hemolysin across the outer membrane of Escherichia coli requires two functions.

This map is an update of the edition 9 map by Berlyn et al. (M. K. B. Berlyn, K. B. Low, and K. E. Rudd, p. 1715–1902, in F. C. Neidhardt et al., ed., Escherichia coli and Salmonella: cellular and molecular biology, 2nd ed., vol. 2, 1996). It uses coordinates established by the completed sequence, expressed as 100 minutes for the entire circular map, and adds new genes discovered and established since 1996 and eliminates those shown to correspond to other known genes. The latter are included as synonyms. An alphabetical list of genes showing map location, synonyms, the protein or RNA product of the gene, phenotypes of mutants, and reference citations is provided. In addition to genes known to correspond to gene sequences, other genes, often older, that are described by phenotype and older mapping techniques and that have not been correlated with sequences are included.

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Linkage Map of Escherichia coli K-12, Edition 10: The Traditional Map

https://www.cell.com/cell/pdf/0092-8674(81)90392-5.pdf

Gene sequence of the λ receptor, an outer membrane protein of E. coli K12

lamB is the structural gene for the bacteriophage lambda receptor in Escherichia coli K-12. In vivo and in vitro studies of the lambda receptor from lamB missence mutants selected as resistant to phage lambda h+ showed the following. (i) Resistance was not due to a change in the amount of lambda receptor protein present in the outer membrane but rather to a change in activity. All of the mutants were still sensitive to phage lambda hh*, a two-step host range mutant of phage lambda h+. Some (10/16) were still sensitive to phage lambda h, a one-step host range mutant. (ii) Resistance occurred either by a loss of binding ability or by a block in a later irreversible step. Among the 16 mutations, 14 affected binding of lambda h+. Two (lamB106 and lamB110) affected inactivation but not binding; they represented the first genetic evidence for a role of the lambda receptor in more than one step of phage inactivation. Similarly, among the six mutations yielding resistance to lambda h, five affected binding and one (lamB109) did not. (iii) The pattern of interactions between the mutated receptors and lambda h+ and its host range mutants were very similar, although not identical, in vivo and in vitro. Defects were usually more visible in vitro than in vivo, the only exception being lamB109. (iv) The ability to use dextrins as a carbon source was not appreciably affected in the mutants. Possible working models and the relations between phage infection and dextrins transport were briefly discussed.

C Braun-Breton

Papers

In vivo and in vitro functional alterations of the bacteriophage lambda receptor in lamB missense mutants of Escherichia coli K-12.