艰难梭菌感染(CDI)仍然是全球重大的公共卫生威胁。治疗CDI的新干预措施依赖于对循环菌株的进化和流行病学的理解。在这里,我们提供了菌株多样性的纵向基因组数据,艰难梭菌核糖型(RT)014/020(n=169)的传播动力学和抗菌素耐药性(AMR),002(n=77)和056(n=36),在澳大利亚引起CDI的三种最突出的艰难梭菌菌株。基因组审查表明AMR在这些谱系中并不常见,具有抗性的等位基因仅存在于15/169RT014/020菌株中(8.9%),1/36RT056株(2.78%),77RT002株无。值得注意的是,~90%的菌株在体外对MLSB试剂具有抗性,但只有约5.9%的人拥有已知的抗性等位基因,突出AMR基因型和表型之间的不一致。核心基因组分析显示,所有三个RT均包含遗传异质性菌株种群,CDI病例之间克隆传播的证据有限。每个RT组内的成对核心基因组SNP(cgSNP)差异的平均数目范围为23.3(RT056,ST34,n=36)至115.6(RT002,ST8,n=77)和315.9(RT014/020,ST2,13,14,49,n=169)。只有19个克隆组(包括40个分离株),定义为差异≤2个cgSNPs的分离株,在所有三个RT(RT014/020,n=14;RT002,n=3;RT056,n=2)中鉴定。在这些克隆群中,63%(12/19)包含来自澳大利亚同一州的分离株,37%(7/19)包含来自不同州的分离株。在这些主要RT(以及先前在动物和环境来源/水库中记录的种群)中发现的合理传播事件的数量很少,这表明了各种艰难梭菌菌株的广泛和持续的社区来源,而不是由单一克隆主导的正在进行的全国性医疗保健爆发。一起,这些数据为澳大利亚引起CDI的主要谱系的演变提供了新的见解,并强调了加强监测的迫切需要,并使公共卫生干预措施超越医疗保健环境,进入“一个健康”范式,以有效对抗这种复杂的病原体。
Clostridioides difficile infection (CDI) remains a significant public health threat globally. New interventions to treat CDI rely on an understanding of the evolution and epidemiology of circulating strains. Here we provide longitudinal genomic data on strain diversity, transmission dynamics and antimicrobial resistance (AMR) of C. difficile ribotypes (RTs) 014/020 (n=169), 002 (n=77) and 056 (n=36), the three most prominent C. difficile strains causing CDI in Australia. Genome scrutiny showed that AMR was uncommon in these lineages, with resistance-conferring alleles present in only 15/169 RT014/020 strains (8.9 %), 1/36 RT056 strains (2.78 %) and none of 77 RT002 strains. Notably, ~90 % of strains were resistant to MLSB agents in vitro, but only ~5.9 % harboured known resistance alleles, highlighting an incongruence between AMR genotype and phenotype. Core genome analyses revealed all three RTs contained genetically heterogeneous strain populations with limited evidence of clonal transmission between CDI cases. The average number of pairwise core genome SNP (cgSNP) differences within each RT group ranged from 23.3 (RT056, ST34, n=36) to 115.6 (RT002, ST8, n=77) and 315.9 (RT014/020, STs 2, 13, 14, 49, n=169). Just 19 clonal groups (encompassing 40 isolates), defined as isolates differing by ≤2 cgSNPs, were identified across all three RTs (RT014/020, n=14; RT002, n=3; RT056, n=2). Of these clonal groups, 63 % (12/19) comprised isolates from the same Australian State and 37 % (7/19) comprised isolates from different States. The low number of plausible transmission events found for these major RTs (and previously documented populations in animal and environmental sources/reservoirs) points to widespread and persistent community sources of diverse C. difficile strains as opposed to ongoing nationwide healthcare outbreaks dominated by a single clone. Together, these data provide new insights into the evolution of major lineages causing CDI in Australia and highlight the urgent need for enhanced surveillance, and for public health interventions to move beyond the healthcare setting and into a One Health paradigm to effectively combat this complex pathogen.