Tissue Microbiology Laboratory, Division of Cellular and Gene Therapies, Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America.
Department of Medicine, Newark Beth Israel Medical Center, Newark, New Jersey, United States of America.
PLoS One. 2013 Dec 18;8(12):e82673. doi: 10.1371/journal.pone.0082673. eCollection 2013.
We recently isolated and discovered new Bradyrhizobiaceae microbes from the cryopreserved culture broth of blood samples from 3 patients with poorly defined illnesses using modified SP4 media and culture conditions coupled with genomic sequencing. Using a similar protocol, we studied a previously cryopreserved culture broth of blood sample from a patient who had succumbed to an acute onset of fulminant pulmonary illness. We report that two phases of microbial growth were observed in the re-initiated culture. Biochemical and genomic characterization revealed microbes isolated from the first phase of growth were new Afipia species of Bradyrhizobiaceae, tentatively named A. cberi with a ~ 5 MB chromosome that was different from those of all previously known Afipia microbes including the newly discovered A. septicemium. The microbes isolated from the second phase of growth were prominent sugar assimilators, novel Phyllobacteriaceae, phylogenetically most closely related to Mesorhizobium and tentatively named M. hominis with a ~ 5.5 MB chromosome. All A. cberi isolates carry a circular ~ 140 KB plasmid. Some M. hominis isolates possess a circular ~ 412 KB plasmid that can be lost in prolonged culture or passage. No antibiotics resistant genes could be identified in both of the A. cberi and M. hominis plasmids. Antibiotic susceptibility studies using broth culture systems revealed isolates of A. cberi could be sensitive to some antibiotics, but all isolates of M. hominis were resistant to essentially all tested antibiotics. However, the cell-free antibiotics susceptibility test results may not be applicable to clinical treatment against the microbes that are known to be capable of intracellular growth. It remains to be determined if the 2 previously unknown Rhizobiales were indeed pathogenic and played a role in the pulmonary disease process in this patient. Specific probes and methods will be developed to re-examine the diseased lungs from patient's autopsy.
我们最近使用改良的 SP4 培养基和培养条件以及基因组测序,从 3 名患有定义不明确疾病的患者的冷冻保存的血液样本的培养肉汤中分离和发现了新的 Bradyrhizobiaceae 微生物。使用类似的方案,我们研究了一名先前死于暴发性肺疾病的患者的冷冻保存的血液样本的培养肉汤。我们报告在重新启动的培养中观察到两个微生物生长阶段。生化和基因组特征表明,从第一阶段生长中分离出的微生物是 Bradyrhizobiaceae 的新 Afipia 种,暂定名为 A. cberi,其染色体约为 5MB,与所有先前已知的 Afipia 微生物(包括新发现的 A. septicemium)不同。从第二阶段生长中分离出的微生物是显著的糖同化剂,是新型的 Phyllobacteriaceae,在系统发育上与 Mesorhizobium 最为密切相关,暂定名为 M. hominis,其染色体约为 5.5MB。所有 A. cberi 分离株都携带一个圆形的约 140KB 质粒。一些 M. hominis 分离株具有一个圆形的约 412KB 质粒,在长时间培养或传代过程中可能会丢失。在 A. cberi 和 M. hominis 质粒中均无法鉴定出抗生素抗性基因。使用肉汤培养系统进行的抗生素敏感性研究表明,A. cberi 分离株可能对一些抗生素敏感,但所有 M. hominis 分离株对基本上所有测试的抗生素均具有抗性。然而,细胞外抗生素敏感性测试结果可能不适用于针对已知能够在细胞内生长的微生物的临床治疗。尚需确定这 2 种以前未知的 Rhizobiales 是否确实具有致病性,并在该患者的肺部疾病过程中发挥作用。将开发特定的探针和方法来重新检查患者尸检的患病肺组织。