Laboratory of Zoonoses and Antibiotic Resistance, Department of Microbiology and Antimicrobial Resistance, Veterinary Research Institute, Brno, Hudcova 296/70, Brno, Czech Republic.
Laboratory of Zoonoses and Antibiotic Resistance, Department of Microbiology and Antimicrobial Resistance, Veterinary Research Institute, Brno, Hudcova 296/70, Brno, Czech Republic.
Toxicon. 2021 Jul 15;197:126-135. doi: 10.1016/j.toxicon.2021.04.007. Epub 2021 Apr 24.
Microbiota can significantly contribute to colorectal cancer initiation and development. It was described that E. coli harbouring polyketide synthase (pks) genes can synthetize bacterial toxin colibactin, which was first described by Nougayrede's group in 2006. E. coli positive for pks genes were overrepresented in colorectal cancer biopsies and, therefore, prevalence and the effect of pks positive bacteria as a risk factor in colorectal cancer development is in our interest. Interestingly, pks gene cluster in E. coli shares a striking 100% sequence identity with K. pneumoniae, suggesting that their function and regulation are conserved. Moreover, K. pneumoniae can express a variety of virulence factors, including capsules, siderophores, iron-scavenging systems, adhesins and endotoxins. It was reported that pks cluster and thereby colibactin is also related to the hypervirulence of K. pneumoniae. Acquisition of the pks locus is associated with K. pneumoniae gut colonisation and mucosal invasion. Colibactin also increases the likelihood of serious complications of bacterial infections, such as development of meningitis and potentially tumorigenesis. Even though K. pneumoniae is undoubtedly a gut colonizer, the role of pks positive K. pneumoniae in GIT has not yet been investigated. It seems that CRC-distinctive microbiota is already present in the early stages of cancer development and, therefore, microbiome analysis could help to discover the early stages of cancer, which are crucial for effectiveness of anticancer therapy. We hypothesize, that pks positive K. pneumoniae can be a potential biomarker of tumour prevalence and anticancer therapy response.
微生物组可以显著促进结直肠癌的发生和发展。据描述，携带聚酮合酶 (pks) 基因的大肠杆菌可以合成细菌毒素 colibactin，这是 Nougayrede 小组于 2006 年首次描述的。在结直肠癌活检中，pks 基因阳性的大肠杆菌过度表达，因此，pks 阳性细菌作为结直肠癌发生的危险因素的流行程度及其影响是我们关注的焦点。有趣的是，大肠杆菌中的 pks 基因簇与肺炎克雷伯氏菌具有惊人的 100%序列同一性，表明它们的功能和调控是保守的。此外，肺炎克雷伯氏菌可以表达多种毒力因子，包括荚膜、铁载体、铁摄取系统、黏附素和内毒素。据报道，pks 簇和 colibactin 也与肺炎克雷伯氏菌的超强毒力有关。pks 基因座的获得与肺炎克雷伯氏菌在肠道的定植和黏膜侵袭有关。colibactin 还增加了细菌感染严重并发症的可能性，例如脑膜炎的发展和潜在的肿瘤发生。尽管肺炎克雷伯氏菌无疑是肠道定植菌，但 pks 阳性肺炎克雷伯氏菌在 GIT 中的作用尚未得到研究。似乎 CRC 特有的微生物组已经存在于癌症发展的早期阶段，因此，微生物组分析可以帮助发现癌症的早期阶段，这对于癌症治疗的效果至关重要。我们假设，pks 阳性肺炎克雷伯氏菌可能是肿瘤患病率和抗癌治疗反应的潜在生物标志物。
