Divergence in the background: hard to measure but the key to being the best of the best

The invention of the gun was a significant gain of function in warfare. Similarly, the acquisition of a virulence determinant, say a type III secretion system encoding a molecular needle to deliver toxic proteins, is a significant gain of function in biological warfare. Such cataclysmic changes in capability are readily detectable above the noise of biological variability. In fact, all of our genetic tools rely on the magnitude of such events to identify virulence determinants. We measure their importance by how great a change occurs with loss of function and whether significant complementation occurs in trans.Sokurenko and colleagues1xSokurenko, E.V., Hastu, D.L., and Dykhuizen, D.E. Trends Microbiol. 1999; 7: 191–196Abstract | Full Text | Full Text PDF | PubMed | Scopus (124)See all References1 propose that a second process, pathoadaptation, changes pathogenicity in parallel with the classical introduction of a new virulence determinant. This process can be likened to giving a new weapon (such as the gun) to several different soldiers and learning that some are more capable than others when out in the battlefield. Differences in genetic background have been very hard to study because the differences in individual capability are small relative to the diversity of the population. The authors make the point that gene mutations are most often selected against and it is difficult to notice the positive changes that accumulate over time.Is pathoadaptation more prominent when the microorganism lives in two or more niches? This would make sense, as the model proposes that pathoadaptation should be more active in a gene that is free to change with little cost. Phase-variable genes, such as those involved in turning fimbrial expression on or off, would be ideal targets as they are not required at all times. Pathoadaptation might be a process that supports the evolution of phase variation. Does pathoadaptation manifest as chronic rather than acute disease? Our current understanding of genetic traits that define chronicity is poor; however, the evolution of a group of determinants that gradually lengthens the time of host–pathogen interactions would facilitate selection for pathoadaptation.To detect this process in action, large numbers of alleles must be sequenced. This step generates a mathematical definition of diversity, in terms of the freedom of genes to be diverse. Examples of such analyses are few, but those cited by Sokurenko for mucoidy in Pseudomonas aeruginosa and mannose adherence in Escherichia coli provide initial, solid evidence.How important is a process of gradual change like pathoadaptation? Presumably, it would be critical when pathogens change niches, thereby testing their breadth of genetic fitness. It would also be important in the emergence of a new capability that is more effective in one background than another. This suggests that background diversity could be tested by assaying the efficiency of use of a major new capability in a number of diverse clones. One would expect that the re-examination of major events, such as the emergence of drug resistance, would reveal key features of the microbial cell most suited to the new tool. This could explain the observation that only a limited number of capsule and cell types are circulating as hypervirulent clones of multidrug-resistant pathogens.