Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
University of Malaya Centre of Proteomics Research (UMCPR), University of Malaya, Kuala Lumpur, Malaysia.
PLoS One. 2020 Jan 28;15(1):e0228217. doi: 10.1371/journal.pone.0228217. eCollection 2020.
Escherichia coli (E. coli) from the B2 phylogenetic group is implicated in colorectal cancer (CRC) as it possesses a genomic island, termed polyketide synthetase (pks), which codes for the synthesis of colibactin, a genotoxin that induces DNA damage, cell cycle arrest, mutations and chromosomal instability in eukaryotic cells. The aim of this study was to detect and compare the prevalence of E. coli expressing pks (pks+ E. coli) in CRC patients and healthy controls followed by investigating the virulence triggered by pks+ E. coli using an in-vitro model. Mucosal colon tissues were collected and processed to determine the presence of pks+ E. coli. Thereafter, primary colon epithelial (PCE) and colorectal carcinoma (HCT116) cell lines were used to detect cytopathic response to the isolated pks+ E. coli strains. Our results showed 16.7% and 4.3% of CRC and healthy controls, respectively were pks+ E. coli. Further, PCE displayed syncytia and cell swelling and HCT116 cells, megalocytosis, in response to treatment with the isolated pks+ E. coli strains. In conclusion, pks+ E. coli was more often isolated from tissue of CRC patients compared to healthy individuals, and our in-vitro assays suggest these isolated strains may be involved in the initiation and development of CRC.
大肠杆菌(E. coli)属于 B2 进化群,与结直肠癌(CRC)有关,因为它具有一个基因组岛,称为聚酮合酶(pks),可编码产生 colibactin,这是一种遗传毒素,可在真核细胞中诱导 DNA 损伤、细胞周期停滞、突变和染色体不稳定性。本研究旨在检测和比较 CRC 患者和健康对照者中表达 pks 的大肠杆菌(pks+ E. coli)的流行率,然后使用体外模型研究 pks+ E. coli 引发的毒力。收集并处理粘膜结肠组织以确定 pks+ E. coli 的存在。然后,使用原代结肠上皮(PCE)和结直肠癌细胞(HCT116)细胞系检测分离的 pks+ E. coli 菌株对细胞的细胞病变效应。我们的结果显示,CRC 患者和健康对照者中 pks+ E. coli 的比例分别为 16.7%和 4.3%。此外,PCE 对分离的 pks+ E. coli 菌株的反应表现为合胞体和细胞肿胀,而 HCT116 细胞则表现为巨细胞症。总之,与健康个体相比,pks+ E. coli 更常从 CRC 患者的组织中分离出来,我们的体外试验表明这些分离株可能参与 CRC 的发生和发展。