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Researchers have observed that Escherichia Coli bacteria found in Crohn’s Crohn’s disease trigger responses when faced with stress as a survivalmechanism.  They multiply massively and colonize bowel cells before replicating in the macrophages thus creating recurrent infections.

1| Escherichia Coli bacteria found in Crohn’s disease trigger responses when faced with stress

Crohn’s disease, still little known, is caused by inflammation of the digestive tract, induced by hyperactivity of the immune defense system. The disease is characterized by gut microbiome imbalance, AIEC (Adherent invasive Escherichia coli) strains especially, in the intestinal flora. The presence of these bacteria in too large numbers, considered to be a threat, induces a strong immune response.

In a recent study published in the PLOS Pathogens journal, the researchers saw that the E.coli bacteria associated with Crohn’s disease respond to stress to survive, multiply in the bowel cells and go on to replicate in the macrophages. As they grow in this hostile environment, part of these bacteria are believed to develop strong antibiotic tolerance.

2| When the AIEC LF82 strain is phagocyted by the macrophages, it induces a change of phenotype

According to the researchers when the AIEC LF82 strain is phagocyted by the macrophages, this induces a change from so-called replicative status to non-replicative status. This change of phenotype results from a response to stress.

In replicative status, the bacteria become tolerant to the stress produced by the macrophages and part of them become intolerant to antibiotics. According to the researchers, at this stage, tolerance is not resistance as it is only a longer-lasting physiological state of the bacteria despite the presence of antibiotics.

Also, the researchers saw that after around ten hours, certain bacteria become replicative again and this leads to an increase in the bacterial population. On waking, the bacteria resume their cycle and are at high risk of being killed by the antibiotics. In this second phase of infection, around 10% of the LF82 population become tolerant to antibiotics. This is explained by the generation of new non-replicative bacteria, which are sometimes tolerant to antibiotics. This replication phase is believed to be specific to LF82 and to numerous AIEC strains according to the researchers’ findings. The latter succeeded in quantitatively evaluating the contribution of each step to the survival and proliferation of AIEC LF82 strains by modeling the infectious process. They conclude that the more aggressive the macrophages, the more the LF82 can take on non-replicative status and therefore become potentially antibiotic-tolerant. This would mean that a portion of antibiotic-tolerant bacteria could be responsible for the survival of the bacterial population in the macrophages involving recurrent infections.

3| Sources

  1. Demarre G, Prudent V, Schenk H, Rousseau E, Bringer MA, Barnich N, Tran Van Nhieu G, Rimsky S, De Monte S, Espéli O, The Crohn's disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages, PLoS Pathog. 2019 Nov 14;15(11):e1008123. doi: 10.1371/journal.ppat.1008123