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Moonlighting Proteins : Novel Virulence Factors in Bacterial Infections (Hardcover) (Brian Henderson)
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Bacterial infection with exogenous pathogens can be thought of as a result of the evolution of specific bacterial behaviours that outwit the vast panoply of host immune defences. Such interactions occur against the background of the vast colonisation of ****** sapiens with its massive and phylogenetically-complex bacterial microbiota, whose interactions with the human host can only be guessed at. At its simplest, bacterial infection can be seen as a dynamic and evolutionarily-constrained competition between the host and the genetically-dynamic bacterial population of the environment. The major defining factor is bacterial virulence which could be defined simply as the population number required to infect a host organism. The fewer organisms required, the more virulent the organism.
However, this has to be seen as a simplistic view of virulence, which is a systems-based phenomenon with emergent properties. Virulence is a systems-based concept which is dependent on the generation, by the bacterium, of molecules which can allow the bacterium to; (i) colonise; (ii) survive the initial colonisation process; (iii) grow and, potentially, form biofilms; (iv) defeat the approaches of the innate immune system; (v) deal with the adaptive immune cells and, finally, survive without killing the host.
The concept of virulence has given rise to the ‘virulence factor’. These will be best known in terms of the terrors of bacterial infection with gas gangrene (caused by Clostridium perfringen), the flesh-eating bacterium (mainly describing Streptococcus pyogenes), with both pathologies being caused by enzymes, and flaccid and tetanic muscle spasms caused by Clostridium botulinum and Clostridium tetani toxins, respectively. Toxins are the main factor that comes to mind when thinking of bacterial virulence. However, they are only one of a range of molecules that aid the bacterium in its colonisation and growth in the human organism. A range of other bacterial virulence factors include molecules which aid bacterial adhesion to matrices and cells, promote bacterial invasion of cells, control bacterial growth, enable bacterial evasion of host immunity, and molecules which allow bacteria to enter low growth states (e.g. dormancy) which decrease their molecular signatures in the host. The formation of the bacterial biofilm involves a range of other virulence factors including those involved in quorum sensing, biofilm dispersion and so on.
The renaissance of Bacteriology over the last 30 years (due to the upsurge in antibiotic resistance) has seen the identification of a wide range of bacterial virulence mechanisms and the discovery of a large number of molecularly-distinct virulence factors, many of which are proteins. Since the early 1990s, it has become clear that amongst these distinct virulence proteins there exist a substantial number of proteins whose main function has nothing to do wit