PT  - JOURNAL ARTICLE
AU  - von Strempel, Alexandra
AU  - Weiss, Anna S.
AU  - Wittmann, Johannes
AU  - Salvado Silva, Marta
AU  - Ring, Diana
AU  - Wortmann, Esther
AU  - Clavel, Thomas
AU  - Debarbieux, Laurent
AU  - Kleigrewe, Karin
AU  - Stecher, Bärbel
TI  - Bacteriophages targeting protective commensals impair resistance against &lt;em&gt;Salmonella&lt;/em&gt; Typhimurium infection in gnotobiotic mice
AID  - 10.1101/2022.09.28.509654
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.28.509654
4099  - http://biorxiv.org/content/early/2022/09/28/2022.09.28.509654.short
4100  - http://biorxiv.org/content/early/2022/09/28/2022.09.28.509654.full
AB  - Gut microbial communities protect the host against a variety of major human gastrointestinal pathogens. Bacteriophages (phages) are ubiquitous in nature and frequently ingested via food and drinking water. Moreover, they are an attractive tool for microbiome engineering due to the lack of known serious adverse effects on the host. However, the functional role of phages within the gastrointestinal microbiome remain poorly understood. Here, we investigated the effects of microbiota-directed phages on infection with the human enteric pathogen Salmonella enterica serovar Typhimurium (S. Tm), using a gnotobiotic mouse model (OMM12) for colonization resistance (CR). We show that phage cocktails targeting Escherichia coli and Enterococcus faecalis acted in a strain-specific manner. They transiently reduced the population density of their respective target before establishing coexistence for up to 9 days. Infection susceptibility to S. Tm was markedly increased at an early time point after phage challenge. Surprisingly, OMM12 mice were more susceptible 7 days after a single phage inoculation, when the targeted bacterial populations were back to pre-phage administration density. The presence of phages that dynamically modulates the density of protective members of the gut microbiota provides opportunities for invasion of bacterial pathogens.Competing Interest StatementThe authors have declared no competing interest.