Browsing by Author "Johnston, Randal N"

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    Defining natural species of bacteria: clear-cut genomic boundaries revealed by a turning point in nucleotide sequence divergence
    (BioMed Central, 2013-07-18) Tang, Le; Li, Yang; Deng, Xia; Johnston, Randal N; Liu, Gui-Rong; Liu, Shu-Lin
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    E. coli diversity: low in colorectal cancer
    (2020-04-06) Tang, Le; Zhou, Yu-Jie; Zhu, Songling; Liang, Gong-Da; Zhuang, He; Zhao, Man-Fei; Chang, Xiao-Yun; Li, Hai-Ning; Liu, Zheng; Guo, Zhi-Rong; Liu, Wei-Qiao; He, Xiaoyan; Wang, Chun-Xiao; Zhao, Dan-Dan; Li, Jia-Jing; Mu, Xiao-Qin; Yao, Bing-Qing; Li, Xia; Li, Yong-Guo; Duo, Li-Bo; Wang, Li; Johnston, Randal N; Zhou, Jin; Zhao, Jing-Bo; Liu, Gui-Rong; Liu, Shu-Lin
    Abstract Background Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. Methods Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. Results We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. Conclusions The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.
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    Enterolactone has stronger effects than enterodiol on ovarian cancer
    (2017-07-24) Liu, Huidi; Liu, Jianrui; Wang, Siwen; Zeng, Zheng; Li, Ting; Liu, Yongfang; Mastriani, Emilio; Li, Qing-Hai; Bao, Hong-Xia; Zhou, Yu-Jie; Wang, Xiaoyu; Hu, Sijing; Gao, Shan; Qi, Yingying; Shen, Zhihang; Wang, Hongyue; Yu, Miao; Gao, Tingting; Johnston, Randal N; Liu, Shu-Lin
    Abstract Background Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. Methods We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. Results The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. Conclusion END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.
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    Genetic boundaries delineate the potential human pathogen Salmonella bongori into discrete lineages: divergence and speciation
    (2019-12-04) Wang, Xiaoyu; Zhu, Songling; Zhao, Jian-Hua; Bao, Hong-Xia; Liu, Huidi; Ding, Tie-Min; Liu, Gui-Rong; Li, Yong-Guo; Johnston, Randal N; Cao, Feng-Lin; Tang, Le; Liu, Shu-Lin
    Abstract Background Salmonella bongori infect mainly cold-blooded hosts, but infections by S. bongori in warm-blooded hosts have been reported. We hypothesized that S. bongori might have diverged into distinct phylogenetic lineages, with some being able to infect warm-blooded hosts. Results To inspect the divergence status of S. bongori, we first completely sequenced the parakeet isolate RKS3044 and compared it with other sequenced S. bongori strains. We found that RKS3044 contained a novel T6SS encoded in a pathogenicity island-like structure, in addition to a T6SS encoded in SPI-22, which is common to all S. bongori strains so far reported. This novel T6SS resembled the SPI-19 T6SS of the warm-blooded host infecting Salmonella Subgroup I lineages. Genomic sequence comparisons revealed different genomic sequence amelioration events among the S. bongori strains, including a unique CTAG tetranucleotide degeneration pattern in RKS3044, suggesting non-overlapping gene pools between RKS3044 and other S. bongori lineages/strains leading to their independent accumulation of genomic variations. We further proved the existence of a clear-cut genetic boundary between RKS3044 and the other S. bongori lineages/strains analyzed in this study. Conclusions The warm-blooded host-infecting S. bongori strain RKS3044 has diverged with distinct genomic features from other S. bongori strains, including a novel T6SS encoded in a previously not reported pathogenicity island-like structure and a unique genomic sequence degeneration pattern. These findings alert cautions about the emergence of new pathogens originating from non-pathogenic ancestors by acquiring specific pathogenic traits.