Abstract
Many studies have been devoted to understand the mechanisms used by pathogenic bacteria to exploit human hosts. These mechanisms are very diverse in the detail, but share commonalities whose quantification should enlighten the evolution of virulence from both a molecular and an ecological perspective. We mined the literature for experimental data on infectious dose of bacterial pathogens in humans (ID50) and also for traits with which ID50 might be associated. These compilations were checked and complemented with genome analyses. We observed that ID50 varies in a continuous way by over 10 orders of magnitude. Low ID50 values are very strongly associated with the capacity of the bacteria to kill professional phagocytes or to survive in the intracellular milieu of these cells. Inversely, high ID50 values are associated with motile and fast-growing bacteria that use quorum-sensing based regulation of virulence factors expression. Infectious dose is not associated with genome size and shows insignificant phylogenetic inertia, in line with frequent virulence shifts associated with the horizontal gene transfer of a small number of virulence factors. Contrary to previous proposals, infectious dose shows little dependence on contact-dependent secretion systems and on the natural route of exposure. When all variables are combined, immune subversion and quorum-sensing are sufficient to explain two thirds of the variance in infectious dose. Our results show the key role of immune subversion in effective human infection by small bacterial populations. They also suggest that cooperative processes might be important for successful infection by bacteria with high ID50. Our results suggest that trade-offs between selection for population growth-related traits and selection for the ability to subvert the immune system shape bacterial infectiousness. Understanding these trade-offs provides guidelines to study the evolution of virulence and in particular the micro-evolutionary paths of emerging pathogens.
Highlights
Bacteria are a significant part of the human body, often establishing commensal or mutualistic interactions with it [1]
Bacteria that are able to kill professional phagocytes or to survive/ replicate in the intracellular milieu of these cells are mentioned throughout this text as being able to ‘‘kill or subvert professional phagocytes’’ or just able to do ‘‘immune subversion’’
Variation in infectious dose is independent of genome size, phylogenetic structure and little affected by route of exposure
Summary
Bacteria are a significant part of the human body, often establishing commensal or mutualistic interactions with it [1]. Bacteria that are able to kill professional phagocytes or to survive/ replicate in the intracellular milieu of these cells are mentioned throughout this text as being able to ‘‘kill or subvert professional phagocytes’’ or just able to do ‘‘immune subversion’’ (see Discussion for possible limitations and extensions of this definition). Such bacteria may not search to escape the immune response but rather to stimulate it. Knowledge of the mechanisms involved in subverting the immune system is important to effectively control virulence in clinical settings, but precise identification of the common themes behind them is essential to understand the evolution of virulence and its mechanisms [11,12,13]
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