Université Sorbonne Paris Nord, INSERM, IAME, Bobigny, France.
APHP, HUPSSD, Hôpital Avicenne, Service de Microbiologie clinique, Bobigny, France.
mSphere. 2024 Oct 29;9(10):e0053024. doi: 10.1128/msphere.00530-24. Epub 2024 Oct 4.
a commensal species of the human gut, is an opportunistic pathogen that can reach extra-intestinal compartments, including the bloodstream and the bladder, among others. In non-immunosuppressed patients, purifying or neutral evolution of populations has been reported in the gut. Conversely, it has been suggested that when migrating to extra-intestinal compartments, genomes undergo diversifying selection as supported by strong evidence for adaptation. The level of genomic polymorphism and the size of the populations translocating from gut to extra-intestinal compartments is largely unknown. To gain insights into the pathophysiology of these translocations, we investigated the level of polymorphism and the evolutionary forces acting on the genomes of 77 isolated from various compartments in three immunosuppressed patients. Each patient had a unique strain, which was a mutator in one case. In all instances, we observed that translocation encompasses much of the genomic diversity present in the gut. The same signature of selection, whether purifying or diversifying, and as anticipated, neutral for mutator isolates, was observed in both the gut and bloodstream. Additionally, we found a limited number of non-specific mutations among compartments for non-mutator isolates. In all cases, urine isolates were dominated by neutral selection. These findings indicate that substantial proportions of populations are undergoing translocation and that they present a complex compartment-specific pattern of selection at the patient level.IMPORTANCEIt has been suggested that intra and extra-intestinal compartments differentially constrain the evolution of strains. Whether host particular conditions, such as immunosuppression, could affect the strain evolutionary trajectories remains understudied. We found that, in immunosuppressed patients, large fractions of gut populations are translocating with variable modifications of the signature of selection for commensal and pathogenic isolates according to the compartment and/or the patient. Such multiple site sampling should be performed in large cohorts of patients to gain a better understanding of extra-intestinal diseases.
一种人体肠道共生菌，是一种机会性病原体，可以到达肠道以外的部位，包括血液和膀胱等。在非免疫抑制患者中，肠道中的种群已经被报道经历了净化或中性进化。相反，有人认为，当迁移到肠道以外的部位时，基因组会经历多样化选择，这得到了适应的有力证据的支持。从肠道到肠道以外的部位转移的基因组多态性水平和种群大小在很大程度上是未知的。为了深入了解这些转移的病理生理学，我们调查了从三名免疫抑制患者的各种部位分离的 77 株的多态性水平和作用于基因组的进化力量。每个患者都有一种独特的菌株，其中一种是突变体。在所有情况下，我们观察到，转移包含了存在于肠道中的大部分基因组多样性。在肠道和血液中都观察到了相同的选择特征，无论是净化还是多样化，并且正如预期的那样，对于突变体分离株是中性的。此外，对于非突变体分离株，在不同的部位之间发现了有限数量的非特异性突变。在所有情况下，尿液分离株都以中性选择为主。这些发现表明，大量的种群正在经历转移，并且在患者水平上呈现出复杂的特定部位的选择模式。
重要性
有人认为，肠道内和肠道外的部位对菌株的进化有不同的限制。宿主特定的条件，如免疫抑制，是否会影响菌株的进化轨迹，这仍然是一个研究不足的问题。我们发现，在免疫抑制患者中，大量的肠道种群正在转移，根据部位和/或患者，共生和致病性分离株的选择特征发生了不同程度的变化。应该在大量的患者队列中进行这种多部位采样，以更好地了解肠道外疾病。
