Taylor Steven L, Leong Lex E X, Sims Sarah K, Keating Rebecca L, Papanicolas Lito E, Richard Alyson, Mobegi Fredrick M, Wesselingh Steve, Burr Lucy D, Rogers Geraint B
SAHMRI Microbiome Research Laboratory, Flinders University College of Medicine and Public Health, Adelaide, SA, Australia; Microbiome and Host Health, South Australia Health and Medical Research Institute, North Terrace, Adelaide, SA, Australia.
Microbiology and Infectious Diseases, SA Pathology, South Australia, Australia.
J Cyst Fibros. 2021 May;20(3):413-420. doi: 10.1016/j.jcf.2020.11.009. Epub 2020 Nov 26.
The emergence of multidrug resistant (MDR) pathogens represents a profound threat to global health. Individuals with CF have amongst the highest cumulative antibiotic exposure of any patient group, including to critically-important last-line agents. While there is little evidence that antibiotic resistance in airway pathogens results in worse clinical outcomes for CF patients, the potential emergence of MDR pathogens in non-respiratory systems, as a consequence of CF care, represents a potential health threat to the wider population, including family and carers.
Stool from 19 adults with CF and 16 healthy adult controls was subjected to metagenomic sequencing, to assess faecal resistome, and culture-based analysis. Resistant isolates were identified phenotypically, and genetic determinants of resistance characterised by whole genome sequencing.
CF and control faecal resistomes differed significantly (P = 0.0003). The proportion of reads that mapped to mobile genetic elements was significantly higher in CF (P = 0.014) and the composition was significantly different (P = 0.0001). Notably, CF patients displayed higher carriage of plasmid-mediated aminoglycoside-modifying genes ant(6)-Ib, aac(6')-Ip, and aph(3')-IIIa (P < 0.01). Culture-based analysis supported higher aminoglycoside resistance, with a higher proportion of aminoglycoside-resistant, Gram-negative bacteria (P < 0.0001). Isolated extended spectrum beta lactamase (ESBL)-positive Escherichia coli from CF stool exhibited phenotypic resistance to tobramycin and gentamicin. Genomic analysis showed co-localisation of both aminoglycoside resistance and ESBL genes, consistent with MDR emergence through horizontal gene transfer.
The carriage of potentially transmissible resistance within the adult CF gut microbiome is considerably greater than in healthy individuals and could contribute to the emergence and dissemination of MDR pathogens.
多重耐药（MDR）病原体的出现对全球健康构成了严重威胁。囊性纤维化（CF）患者是所有患者群体中累积抗生素暴露量最高的群体之一，包括接触至关重要的最后一线药物。虽然几乎没有证据表明气道病原体中的抗生素耐药性会导致CF患者出现更差的临床结局，但CF治疗导致非呼吸系统中MDR病原体的潜在出现，对包括家人和护理人员在内的更广泛人群构成了潜在的健康威胁。
对19名成年CF患者和16名健康成年对照的粪便进行宏基因组测序，以评估粪便耐药组，并进行基于培养的分析。通过表型鉴定耐药菌株，并通过全基因组测序对耐药的遗传决定因素进行表征。
CF患者和对照的粪便耐药组存在显著差异（P = 0.0003）。映射到移动遗传元件上的读数比例在CF患者中显著更高（P = 0.014），且组成存在显著差异（P = 0.0001）。值得注意的是，CF患者携带质粒介导的氨基糖苷类修饰基因ant(6)-Ib、aac(6')-Ip和aph(3')-IIIa的比例更高（P < 0.01）。基于培养的分析支持更高的氨基糖苷类耐药性，氨基糖苷类耐药的革兰氏阴性菌比例更高（P < 0.0001）。从CF患者粪便中分离出的产超广谱β-内酰胺酶（ESBL）的大肠杆菌对妥布霉素和庆大霉素表现出表型耐药性。基因组分析显示氨基糖苷类耐药基因和ESBL基因共定位，这与通过水平基因转移产生MDR一致。
成年CF患者肠道微生物群中潜在可传播耐药性的携带情况比健康个体高得多，可能导致MDR病原体的出现和传播。
