Inflammation boosts bacteriophage transfer between
            <i>Salmonella</i>
            spp.

Diard, Médéric; Bakkeren, Erik; Cornuault, Jeffrey K.; Moor, Kathrin; Hausmann, Annika; Sellin, Mikael E.; Loverdo, Claude; Aertsen, Abram; Ackermann, Martin; Paepe, Marianne De; Slack, Emma; Hardt, Wolf‐Dietrich

doi:10.1126/science.aaf8451

Cited by 152 publications

(154 citation statements)

References 45 publications

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“…This clustering may reduce inflammation and horizontal gene transfer (Diard et al. ). Here, we shed light on another original effect of clustering: the reduced bacterial diversity resulting from this clustering could hinder the spread of adaptive mutations in a population of hosts, even if the total number of bacteria in a host remains the same.…”

Section: Discussionmentioning

confidence: 99%

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Antibody‐mediated crosslinking of gut bacteria hinders the spread of antibiotic resistance

et al. 2019

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The body is home to a diverse microbiota, mainly in the gut. Resistant bacteria are selected by antibiotic treatments, and once resistance becomes widespread in a population of hosts, antibiotics become useless. Here, we develop a multiscale model of the interaction between antibiotic use and resistance spread in a host population, focusing on an important aspect of within‐host immunity. Antibodies secreted in the gut enchain bacteria upon division, yielding clonal clusters of bacteria. We demonstrate that immunity‐driven bacteria clustering can hinder the spread of a novel resistant bacterial strain in a host population. We quantify this effect both in the case where resistance preexists and in the case where acquiring a new resistance mutation is necessary for the bacteria to spread. We further show that the reduction of spread by clustering can be countered when immune hosts are silent carriers, and are less likely to get treated, and/or have more contacts. We demonstrate the robustness of our findings to including stochastic within‐host bacterial growth, a fitness cost of resistance, and its compensation. Our results highlight the importance of interactions between immunity and the spread of antibiotic resistance, and argue in the favor of vaccine‐based strategies to combat antibiotic resistance.

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Section: Discussionmentioning

confidence: 99%

“…Enchained growth thus constitutes a possible mechanism for acquired immunity to dampen horizontal transfer in the gut (Diard et al. ). Furthermore, since IgA‐mediated clusters of bacteria are mostly clonal, horizontal transfer would most likely occur between very closely related neighboring bacteria, which makes it inefficient at providing new genes.…”

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confidence: 99%

Antibody‐mediated crosslinking of gut bacteria hinders the spread of antibiotic resistance

et al. 2019

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“…Second, the main driver of temperate phage reactivation in the gut lumen is inflammation . Secretory IgA‐driven clumping, via either classical agglutination or enchained growth, leads to inhibition of virulence mechanisms that require contact with gut epithelial cells.…”

Section: Determinants and Consequences Of Clumpingmentioning

confidence: 99%

“…A second alternative relies on the indirect effects of sIgA‐driven clumping/immune exclusion on the total bacterial ecosystem in the gut. As discussed above, any inflammatory signals, which may be inhibited when sIgA is present, are expected to have major consequences ranging from altering intestinal motility and concentrations of electron acceptors to changing the rate of reactivation of temperate phage, and to changing intestinal transit time (potentially affecting clearance rates of all species present in the gut). Moreover, generating or altering community structure through sIgA‐mediated clumping may influence cross‐feeding and therefore growth rates in both targeted and untargeted species, as has been observed in biofilms .…”

Section: Determinants and Consequences Of Clumpingmentioning

confidence: 99%

Growing, evolving and sticking in a flowing environment: understanding IgA interactions with bacteria in the gut

et al. 2019

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Summary Immunology research in the last 50 years has made huge progress in understanding the mechanisms of anti‐bacterial defense of deep, normally sterile, tissues such as blood, spleen and peripheral lymph nodes. In the intestine, with its dense commensal microbiota, it seems rare that this knowledge can be simply translated. Here we put forward the idea that perhaps it is not always the theory of immunology that is lacking to explain mucosal immunity, but rather that we have overlooked crucial parts of the mucosal immunological language required for its translation: namely intestinal and bacterial physiology. We will try to explain this in the context of intestinal secretory antibodies (mainly secretory IgA), which have been described to prevent, to alter, to not affect, or to promote colonization of the intestine and gut‐draining lymphoid tissues, and where effector mechanisms have remained elusive. In fact, these apparently contradictory outcomes can be generated by combining the basic premises of bacterial agglutination with an understanding of bacterial growth (i.e. secretory IgA‐driven enchained growth), fluid handling and bacterial competition in the gut lumen.

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“…Inflammation driven alterations of intestinal phages have been demonstrated during intestinal colitis (Duerkop et al, 2018). During Salmonella enterica serovar Typhimurium infection of the mouse intestine, inflammation enhances prophage induction, virion formation and phage transmission to susceptible hosts (Diard et al, 2017). Together, these observations begin to set a narrative for the myriad of intestinal environmental cues that contribute to phage production.…”

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confidence: 99%