Chapter 5 : Basic Processes in -Host Interactions: Within-Host Evolution and the Transmission of the Virulent Genotype

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In line with Koch’s postulates, studying virulence typically translates into identifying and characterizing the molecular determinants that underlie colonization of a host by a pathogen and the subsequent appearance of symptoms ( ). In this conceptual framework, the presence of pathogens implies damage to the host whose intensity is proportional to the virulence of the pathogen. This approach is based on the observation that damage is often related to the expression of specific features of the pathogen, i.e., the virulence factors ( ).

Citation: Diard M, Hardt W. 2019. Basic Processes in -Host Interactions: Within-Host Evolution and the Transmission of the Virulent Genotype, p 81-94. In Baquero F, Bouza E, Gutiérrez-Fuentes J, Coque T (ed), Microbial Transmission. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MTBP-0012-2016
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Figure 1

The different steps of the gut infection cycle by Typhimurium. Red arrows depict the potential for Typhimurium ( Tm) transmission to the next host during each step. Blue- and red-colored cells depict healthy and inflamed guts, respectively. PMN, polymorphonuclear neutrophils; DC, dendritic cells; MΦ, macrophages; IgA/G, immunoglobulin A/G produced as part of the host’s adaptive immune response 2 weeks postinfection—this follows the regrowth of (2nd bloom) after a population bottleneck inflicted by the innate immune response (at day 2 postinfection); IL-18, interleukin-18; Casp-1, caspase-1.

Citation: Diard M, Hardt W. 2019. Basic Processes in -Host Interactions: Within-Host Evolution and the Transmission of the Virulent Genotype, p 81-94. In Baquero F, Bouza E, Gutiérrez-Fuentes J, Coque T (ed), Microbial Transmission. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MTBP-0012-2016
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Figure 2

The division of labor and the rise of defectors. (A) (Left) Bimodal expression of . The population of Typhimurium is divided into cells that express and cells that do not. (Right) Microscopy picture showing microcolonies on an agar pad of slow-growing “on” cells (expressing green fluorescent protein [GFP] under the control of P, the promoter controlling the SPI-1 operon ) and fast-growing “off” cells. Reproduced with permission from reference . (B) The “on” cells enter into the mucosa and trigger inflammation. Most of these cells are killed by the mucosal innate immune response. Moreover, expression correlates with a substantial growth retardation. The “off” cells grow quickly in the lumen, ensuring the transmission of the virulent genotype. The inflammation is a public good shared among all cells in the lumen. (C) Colony blot obtained and described in reference . Within-host evolution of Typhimurium leads to the rise of avirulent mutants (defectors), which are clones that do not express . The frequency of defectors was increasing between day 2 and day 10 postinfection (p.i.).

Citation: Diard M, Hardt W. 2019. Basic Processes in -Host Interactions: Within-Host Evolution and the Transmission of the Virulent Genotype, p 81-94. In Baquero F, Bouza E, Gutiérrez-Fuentes J, Coque T (ed), Microbial Transmission. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MTBP-0012-2016
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Figure 3

Antibiotic treatments select for virulent clones of Typhimurium able to form persisters in the host tissues. (Left) In the absence of antibiotics, defectors can reach fixation and their transmission to the next host prevents disease. (Right) Antibiotics kill all cells in the lumen: defectors ( mutants) and virulent wild-type () cooperators. However, cells survive in the tissues and can reseed the lumen upon antibiotic withdrawal. This leads to successful transmission of the virulent genotype to the next hosts. Reproduced with permission from reference .

Citation: Diard M, Hardt W. 2019. Basic Processes in -Host Interactions: Within-Host Evolution and the Transmission of the Virulent Genotype, p 81-94. In Baquero F, Bouza E, Gutiérrez-Fuentes J, Coque T (ed), Microbial Transmission. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MTBP-0012-2016
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Asymptomatic carriage of bona fide pathogenic bacteria in humans

Citation: Diard M, Hardt W. 2019. Basic Processes in -Host Interactions: Within-Host Evolution and the Transmission of the Virulent Genotype, p 81-94. In Baquero F, Bouza E, Gutiérrez-Fuentes J, Coque T (ed), Microbial Transmission. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MTBP-0012-2016

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