genomic plasticity

基因组可塑性
  • 文章类型: Journal Article
    蓝细菌是产生氧气的光合细菌,其在暴露于阳光时将二氧化碳转化为生物质。然而,有利的条件会导致有害的蓝藻水华(HCBs),它们是生物质在水面或地下的密集积累,对淡水生态系统和人类健康构成威胁。了解蓝藻水华形成的潜在机制对于有效管理至关重要。在这方面,组学技术的最新进展为HCBs提供了有价值的见解,这提高了人们对在不久的将来开发更有效的控制方法的期望。这篇系统的文献综述旨在介绍基因组结构,自适应机制,微生物相互作用,以及通过组学的视角对六氯联苯的生态影响。基因组分析表明,蓝藻的基因组可塑性使其具有韧性并有效适应环境变化。转录组研究表明,蓝细菌使用各种策略来适应环境压力。此外,宏基因组和代谢组学分析强调了微生物群落在调节HCBs中的重要作用。最后,我们为这一领域的进一步研究提供了潜在机会的观点。
    Cyanobacteria are oxygen-producing photosynthetic bacteria that convert carbon dioxide into biomass upon exposure to sunlight. However, favorable conditions cause harmful cyanobacterial blooms (HCBs), which are the dense accumulation of biomass at the water surface or subsurface, posing threats to freshwater ecosystems and human health. Understanding the mechanisms underlying cyanobacterial bloom formation is crucial for effective management. In this regard, recent advancements in omics technologies have provided valuable insights into HCBs, which have raised expectations to develop more effective control methods in the near future. This literature review aims to present the genomic architecture, adaptive mechanisms, microbial interactions, and ecological impacts of HCBs through the lens of omics. Genomic analysis indicates that the genome plasticity of cyanobacteria has enabled their resilience and effective adaptation to environmental changes. Transcriptomic investigations have revealed that cyanobacteria use various strategies for adapting to environmental stress. Additionally, metagenomic and metatranscriptomic analyses have emphasized the significant role of the microbial community in regulating HCBs. Finally, we offer perspectives on potential opportunities for further research in this field.
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  • 文章类型: Journal Article
    动物宿主藏有不同的微生物共生体组合,在宿主的生活方式中起着至关重要的作用。微生物共生与宿主发育之间的联系仍然知之甚少。特别是,对宿主-微生物共生中肠道细菌的适应性进化知之甚少。最近,共生关系被归类为开放的,关闭,或混合,反映它们的宿主间传播方式,并导致不同的基因组特征。拟杆菌属的成员是最丰富的人类肠道微生物群,具有益生菌和致病潜力。为研究共生系统中的泛基因组进化提供了一个极好的模型。这里,我们确定了一个新的临床菌株PL2022的完整基因组,该菌株是从血液样本中分离的,并对一组代表性的纤维素类拟杆菌菌株进行了全基因组分析,以量化共生关系对进化动力学的影响.B.cellulosilyciticus表现出相关的基因组特征与开放和封闭的共生,暗示了混合共生。一个开放的泛基因组的特征是丰富的附属基因家族,潜在水平基因转移(HGT),和不同的移动遗传元件(MGEs),表明了一个创新的基因库,主要与基因组岛和质粒有关。然而,大量平行基因丢失,弱净化选择,和阳性选择的突变的积累是基因组减少的主要驱动因素。宏基因组阅读招募分析显示,在人类肠道栖息地,符合人体肠道中主要的垂直传播。然而,在非肠组织中也检测到存在和/或高丰度,其他动物宿主,和非主机环境,表示偶尔水平传输到新的壁龛,从而为获得新基因创造了舞台。在混合宿主-微生物共生下的适应性进化的案例研究促进了我们对共生泛基因组进化的理解。我们的结果强调了这种不寻常的肠道共生体中遗传进化的复杂性。
    Animal hosts harbor diverse assemblages of microbial symbionts that play crucial roles in the host\'s lifestyle. The link between microbial symbiosis and host development remains poorly understood. In particular, little is known about the adaptive evolution of gut bacteria in host-microbe symbioses. Recently, symbiotic relationships have been categorized as open, closed, or mixed, reflecting their modes of inter-host transmission and resulting in distinct genomic features. Members of the genus Bacteroides are the most abundant human gut microbiota and possess both probiotic and pathogenic potential, providing an excellent model for studying pan-genome evolution in symbiotic systems. Here, we determined the complete genome of an novel clinical strain PL2022, which was isolated from a blood sample and performed pan-genome analyses on a representative set of Bacteroides cellulosilyticus strains to quantify the influence of the symbiotic relationship on the evolutionary dynamics. B. cellulosilyticus exhibited correlated genomic features with both open and closed symbioses, suggesting a mixed symbiosis. An open pan-genome is characterized by abundant accessory gene families, potential horizontal gene transfer (HGT), and diverse mobile genetic elements (MGEs), indicating an innovative gene pool, mainly associated with genomic islands and plasmids. However, massive parallel gene loss, weak purifying selection, and accumulation of positively selected mutations were the main drivers of genome reduction in B. cellulosilyticus. Metagenomic read recruitment analyses showed that B. cellulosilyticus members are globally distributed and active in human gut habitats, in line with predominant vertical transmission in the human gut. However, existence and/or high abundance were also detected in non-intestinal tissues, other animal hosts, and non-host environments, indicating occasional horizontal transmission to new niches, thereby creating arenas for the acquisition of novel genes. This case study of adaptive evolution under a mixed host-microbe symbiosis advances our understanding of symbiotic pan-genome evolution. Our results highlight the complexity of genetic evolution in this unusual intestinal symbiont.
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  • 文章类型: Review
    铜绿假单胞菌是最通用的细菌之一,具有著名的致病性和广泛的耐药性。这种细菌的不同栖息地包括新鲜的,盐水和排水,土壤,潮湿的表面,水龙头,淋浴喷头,管道,医疗植入物,线虫,昆虫,植物,动物,鸟类和人类。铜绿假单胞菌产生的毒力因子包括绿脓苷,鼠李糖脂,铁载体,裂解酶,毒素和多糖。所有这些有毒元素加上内在的,适应性和获得性抗生素抗性促进不同宿主的持续定植和致死性感染。迄今为止,由于医院获得性铜绿假单胞菌引发的慢性继发感染,肺部疾病的治疗仍然很复杂。相反,这种细菌可以通过抑制植物病原体和昆虫来改善植物生长。值得注意的是,铜绿假单胞菌是极少数能够跨王国传播和感染的细菌之一。将铜绿假单胞菌菌株从植物材料转移到医院病房,动物对人类,和人类对他们的宠物发生相对频繁。最近,我们已经确定植物相关铜绿假单胞菌菌株在病理上可能与临床分离株相似。在这次审查中,我们强调了促进铜绿假单胞菌在不同生物王国中占主导地位的基因组和代谢因素,以及这种细菌在植物和人类健康中的不同作用。
    Pseudomonas aeruginosa is one of the most versatile bacteria with renowned pathogenicity and extensive drug resistance. The diverse habitats of this bacterium include fresh, saline and drainage waters, soil, moist surfaces, taps, showerheads, pipelines, medical implants, nematodes, insects, plants, animals, birds and humans. The arsenal of virulence factors produced by P. aeruginosa includes pyocyanin, rhamnolipids, siderophores, lytic enzymes, toxins and polysaccharides. All these virulent elements coupled with intrinsic, adaptive and acquired antibiotic resistance facilitate persistent colonization and lethal infections in different hosts. To date, treating pulmonary diseases remains complicated due to the chronic secondary infections triggered by hospital-acquired P. aeruginosa. On the contrary, this bacterium can improve plant growth by suppressing phytopathogens and insects. Notably, P. aeruginosa is one of the very few bacteria capable of trans-kingdom transmission and infection. Transfer of P. aeruginosa strains from plant materials to hospital wards, animals to humans, and humans to their pets occurs relatively often. Recently, we have identified that plant-associated P. aeruginosa strains could be pathologically similar to clinical isolates. In this review, we have highlighted the genomic and metabolic factors that facilitate the dominance of P. aeruginosa across different biological kingdoms and the varying roles of this bacterium in plant and human health.
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  • 文章类型: Journal Article
    由于农杆菌具有转化真核细胞的能力,因此对于植物基因工程和农业生物技术的发展至关重要。然而,基因组成,进化动力学,这个物种的生态位适应仍然是未知的。因此,我们建立了基于全染色体数据集的比较基因组分析,以评估A.fabrum的遗传多样性。这里,通过核心基因组系统发育与平均核苷酸同一性(ANI)相结合,选择了25A。氨基酸同一性(AAI),和计算机DNA-DNA杂交(DDH)值。A.fabrum的开放泛基因组表现出具有可变辅助基因的遗传多样性,如12个代表性基因组的共有泛基因组所证明的。A.fabrum的基因组可塑性在其推定的可移动遗传元件(MGE)序列中很明显,有限的水平基因转移障碍,和潜在的水平转移基因。使用eggNOG-mapper软件通过直系同源群(COG)类别测量了泛染色体中的进化约束和功能富集,使用HYPHY软件确定非同义/同义比率(dN/dS)。比较分析显示,核心基因组和非核心基因组之间的功能富集和纯化选择程度存在显着差异。我们证明,核心基因家族经历了更强的纯化选择,但具有包含一个或多个正选择位点的显着偏见。此外,尽管它们具有相似的遗传多样性,我们观察到染色体1(ChrI)和染色体在功能特征和进化限制方面的显着差异。我们证明了负责植物感染的推定遗传元件,生态适应,物种形成代表核心基因组,强调了它们在使A.fabrum适应与植物相关的生态位方面的重要性。我们对A.fabrum的泛染色体分析提供了对遗传特性的全面见解,进化模式,和物种的生态位适应。重要性农杆菌属。生活在不同的植物相关的生态位,如土壤,根际,和植被,它们受到多种压力源的挑战,比如不同的能源,植物防御,微生物竞争他们进化了利用各种资源的能力,逃离植物防御,打败竞争对手。然而,农杆菌的遗传多样性和进化动态。仍未探索。我们检查了A的系统发育和全基因组,以定义种内进化关系。我们的结果表明,在A.fabrum基因组中存在开放的泛基因组和许多MGE和水平转移的基因,反映了染色体的灵活性和遗传交换的潜力。此外,我们观察到核心和辅助基因组之间以及ChrI和染色体之间的功能特征和进化约束的显着差异,分别。
    Agrobacterium fabrum has been critical for the development of plant genetic engineering and agricultural biotechnology due to its ability to transform eukaryotic cells. However, the gene composition, evolutionary dynamics, and niche adaptation of this species is still unknown. Therefore, we established a comparative genomic analysis based on a pan-chromosome data set to evaluate the genetic diversity of A. fabrum. Here, 25 A. fabrum genomes were selected for analysis by core genome phylogeny combined with the average nucleotide identity (ANI), amino acid identity (AAI), and in silico DNA-DNA hybridization (DDH) values. An open pan-genome of A. fabrum exhibits genetic diversity with variable accessorial genes as evidenced by a consensus pan-genome of 12 representative genomes. The genomic plasticity of A. fabrum is apparent in its putative sequences for mobile genetic elements (MGEs), limited horizontal gene transfer barriers, and potentially horizontally transferred genes. The evolutionary constraints and functional enrichment in the pan-chromosome were measured by the Clusters of Orthologous Groups (COG) categories using eggNOG-mapper software, and the nonsynonymous/synonymous rate ratio (dN/dS) was determined using HYPHY software. Comparative analysis revealed significant differences in the functional enrichment and the degree of purifying selection between the core genome and non-core genome. We demonstrate that the core gene families undergo stronger purifying selection but have a significant bias to contain one or more positively selected sites. Furthermore, although they shared similar genetic diversity, we observed significant differences between chromosome 1 (Chr I) and the chromid in their functional features and evolutionary constraints. We demonstrate that putative genetic elements responsible for plant infection, ecological adaptation, and speciation represent the core genome, highlighting their importance in the adaptation of A. fabrum to plant-related niches. Our pan-chromosome analysis of A. fabrum provides comprehensive insights into the genetic properties, evolutionary patterns, and niche adaptation of the species. IMPORTANCE Agrobacterium spp. live in diverse plant-associated niches such as soil, the rhizosphere, and vegetation, which are challenged by multiple stressors such as diverse energy sources, plant defenses, and microbial competition. They have evolved the ability to utilize diverse resources, escape plant defenses, and defeat competitors. However, the underlying genetic diversity and evolutionary dynamics of Agrobacterium spp. remain unexplored. We examined the phylogeny and pan-genome of A. fabrum to define intraspecies evolutionary relationships. Our results indicate an open pan-genome and numerous MGEs and horizontally transferred genes among A. fabrum genomes, reflecting the flexibility of the chromosomes and the potential for genetic exchange. Furthermore, we observed significant differences in the functional features and evolutionary constraints between the core and accessory genomes and between Chr I and the chromid, respectively.
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  • 文章类型: Journal Article
    产生的大量细菌基因组数据促进了用于泛基因组研究的细菌的深入分析。然而,一个物种的泛基因组组成在不同的研究之间存在显著差异,因此,我们使用金黄色葡萄球菌作为模型生物来探索驱动细菌泛基因组组成的影响。我们选择了一系列不同的菌株进行泛基因组分析,以探索金黄色葡萄球菌在物种水平上的泛基因组组成以及影响因素的实际贡献(序列类型[ST],隔离源,孤立的国家,和收集日期)以泛基因组组成。我们发现,在不同条件下抑制的细菌种群中核心基因的分布显着不同,并且在同一ST中显示出“局部核心基因区域”。因此,我们认为ST可能是驱动细菌基因组动态分布的关键因素,并且使用全基因组比对的系统发育分析在包含多个ST菌株的群体中不再合适.全基因组分析表明,在金黄色葡萄球菌菌株中,多位点序列分型(MLST)的某些持家基因的携带率低于60%。因此,我们提出了一组新的用于金黄色葡萄球菌分类的标记基因,这为寻找一套新的管家基因应用于MLST提供了参考。在这项研究中,我们探讨了影响泛基因组组成的驱动因素的作用,为细菌泛基因组的研究提供新的见解。重要性我们试图探索使用金黄色葡萄球菌作为模型生物影响泛基因组组成的驱动因素的影响,为细菌泛基因组的研究提供新的见解。我们认为,所考虑的菌株的序列类型(ST)在细菌基因的动态分布中起着重要作用。我们的发现表明,金黄色葡萄球菌中存在一定数量的必需基因;然而,核心基因的数量没有以前想象的那么多。本文提出的新分类方法表明,必须鉴定更适合金黄色葡萄球菌的一组新的管家基因,以改善该物种的当前分类状态。
    The massive quantities of bacterial genomic data being generated have facilitated in-depth analyses of bacteria for pan-genomic studies. However, the pan-genome compositions of one species differed significantly between different studies, so we used Staphylococcus aureus as a model organism to explore the influences driving bacterial pan-genome composition. We selected a series of diverse strains for pan-genomic analysis to explore the pan-genomic composition of S. aureus at the species level and the actual contribution of influencing factors (sequence type [ST], source of isolation, country of isolation, and date of collection) to pan-genome composition. We found that the distribution of core genes in bacterial populations restrained under different conditions differed significantly and showed \"local core gene regions\" in the same ST. Therefore, we propose that ST may be a key factor driving the dynamic distribution of bacterial genomes and that phylogenetic analyses using whole-genome alignment are no longer appropriate in populations containing multiple ST strains. Pan-genomic analysis showed that some of the housekeeping genes of multilocus sequence typing (MLST) are carried at less than 60% in S. aureus strains. Consequently, we propose a new set of marker genes for the classification of S. aureus, which provides a reference for finding a new set of housekeeping genes to apply to MLST. In this study, we explored the role of driving factors influencing pan-genome composition, providing new insights into the study of bacterial pan-genomes. IMPORTANCE We sought to explore the impact of driving factors influencing pan-genome composition using Staphylococcus aureus as a model organism to provide new insights for the study of bacterial pan-genomes. We believe that the sequence type (ST) of the strains under consideration plays a significant role in the dynamic distribution of bacterial genes. Our findings indicate that there are a certain number of essential genes in Staphylococcus aureus; however, the number of core genes is not as high as previously thought. The new classification method proposed herein suggests that a new set of housekeeping genes more suitable for Staphylococcus aureus must be identified to improve the current classification status of this species.
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  • 文章类型: Journal Article
    大规模基因组研究已将宿主内适应确定为细菌感染的标志。然而,生理的影响,新陈代谢,不同生态位之间对机会性病原体的病理适应的免疫学差异仍然难以捉摸。这里,我们分析了从123例尿路感染患者的胃肠道和泌尿道纵向取样的976个分离株的宿主内适应和进化轨迹,这些分离株代表119个泌尿致病性大肠杆菌(UPEC)谱系.我们表明,在患者体内的两个生态位中持续存在的谱系表现出增加的等位基因多样性。生境特异性选择导致生态位特异性适应性突变和基因,在两种环境中都可以推定调节健身。由可移动遗传元件(MGEs)介导的谱系内生境间基因组可塑性为机会性病原体提供了适应任一生境生理条件的机制。MGE丰富度降低与肠道适应UPEC谱系的复发有关。总的来说,我们的结果确立了生态位特异性适应作为UPEC宿主内进化的驱动因素。
    Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution.
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  • 文章类型: Journal Article
    联合抗逆转录病毒疗法(cART)是在没有有效疫苗的情况下预防和控制HIV-1感染的最有效工具。然而,HIV-1耐药突变(DRMs)和自然发生的多态性(NOPs)可以消除cART功效。这里,我们旨在描述喀麦隆的HIV-1pol突变情况,高度多样化的艾滋病毒分支在那里传播,并鉴定可能影响cART疗效的新型治疗相关突变。从1987年到2020年,研究了8,000多个功能性喀麦隆HIV-1pol序列的DRM和NOP。确定并比较了cART区域实施之前(≤2003年)和之后(2004-2020年)的特定位置氨基酸频率和四级结构特征。cART在喀麦隆的使用诱导了逆转录酶(RT)和蛋白酶(PR)和整合酶(IN)的深度突变印记,根据他们的相对用法。在主要的循环重组形式(CRF)02_AG(CRF02_AG)中,在cART放大期间,RT中有27个规范的DRM和29个NOP显着增加或减少,而在IN,没有DRM,只有七个NOP发生了重大变化。与PR和IN相比,RT中DRM的深刻基因组印记和更高的患病率反映了逆转录酶抑制剂(RTIs)在撒哈拉以南非洲和主要是整合酶链转移抑制剂(InSTI)-幼稚研究人群中的主要使用。我们的结果支持InSTIs在喀麦隆抗逆转录病毒治疗的潜力;然而,需要密切监测IN突变,以识别新出现的耐药模式,如在RT和PR中观察到的。全人群基因组分析有助于揭示选择性压力和病毒适应过程的存在,以指导绕过耐药性和恢复有效治疗的策略。
    Combinational antiretroviral therapy (cART) is the most effective tool to prevent and control HIV-1 infection without an effective vaccine. However, HIV-1 drug resistance mutations (DRMs) and naturally occurring polymorphisms (NOPs) can abrogate cART efficacy. Here, we aimed to characterize the HIV-1 pol mutation landscape in Cameroon, where highly diverse HIV clades circulate, and identify novel treatment-associated mutations that can potentially affect cART efficacy. More than 8,000 functional Cameroonian HIV-1 pol sequences from 1987 to 2020 were studied for DRMs and NOPs. Site-specific amino acid frequencies and quaternary structural features were determined and compared between periods before (≤2003) and after (2004-2020) regional implementation of cART. cART usage in Cameroon induced deep mutation imprints in reverse transcriptase (RT) and to a lower extent in protease (PR) and integrase (IN), according to their relative usage. In the predominant circulating recombinant form (CRF) 02_AG (CRF02_AG), 27 canonical DRMs and 29 NOPs significantly increased or decreased in RT during cART scale-up, whereas in IN, no DRM and only seven NOPs significantly changed. The profound genomic imprints and higher prevalence of DRMs in RT compared to PR and IN mirror the dominant use of reverse transcriptase inhibitors (RTIs) in sub-Saharan Africa and the predominantly integrase strand transfer inhibitor (InSTI)-naïve study population. Our results support the potential of InSTIs for antiretroviral treatment in Cameroon; however, close surveillance of IN mutations will be required to identify emerging resistance patterns, as observed in RT and PR. Population-wide genomic analyses help reveal the presence of selective pressures and viral adaptation processes to guide strategies to bypass resistance and reinstate effective treatment.
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  • 文章类型: Journal Article
    肺炎克雷伯菌碳青霉烯酶(KPCs)的多重耐药革兰氏阴性携带者通常由于实验室检测灵敏度不足而破坏抗生素治疗。尽管不稳定的基因扩增已被认为是导致低估或误判临床分离株抗菌素耐药性的关键原因,由blaKPC-2扩增驱动的碳青霉烯抵抗的确切机制仍然不清楚。这里,我们报道,在亚致死的美罗培南或妥布霉素预暴露后,IS26介导的blaKPC-2扩增迅速而有力地导致了大肠杆菌临床菌株的碳青霉烯类耐药表型.有趣的是,IS26还支持包括9个抗生素抗性基因和6个IS26插入序列的47kb多药抗性(MDR)区域的扩增。串联重复分析和实验验证表明,blaKPC-2扩增确实是由IS26介导的,进一步的实验表明,IS26涉及复杂的遗传重排。这种基因扩增在抗生素胁迫下动态产生,并在抗生素停药后消退。而不是减少IS26侧翼MDR区的扩增,体外药物组合加剧了这种情况。我们的研究,因此,提供了有关动态基因扩增过程如何急剧改变抗性状态并使诊断复杂化的有价值的见解。重要性肺炎克雷伯菌碳青霉烯酶(KPCs)是强大的β-内酰胺酶,使革兰氏阴性病原体破坏临床上重要的碳青霉烯类抗生素治疗。特别是,由于在常规实验室屏幕中缺乏仪器灵敏度,KPC-2难以检测,这导致误诊和不良的治疗结果。目前尚不清楚blaKPC-2如何在亚致死抗生素的挑战后迅速诱导对碳青霉烯类抗生素的高水平耐药性。这里,我们证明了,在亚致死剂量的抗生素下,插入序列IS26介导多个抗性决定子的快速扩增,包括BlaKPC-2和多重耐药(MDR)区域,伴随着复杂的基因重排。
    Multidrug-resistant Gram-negative carriers of Klebsiella pneumoniae carbapenemases (KPCs) often subvert antibiotic therapy due to inadequate sensitivity in laboratory detection. Although unstable gene amplification has been recognized to crucially contribute to underestimation or misestimation of antimicrobial resistance in clinical isolates, the precise mechanisms underlying carbapenem resistance driven by amplification of blaKPC-2 remain obscure. Here, we reported that IS26-mediated amplification of blaKPC-2 rapidly and robustly gave rise to carbapenem hyperresistant phenotypes in an Escherichia coli clinical strain following sublethal meropenem or tobramycin preexposure. Intriguingly, IS26 also underpinned amplification of a 47 kb multiple drug resistance (MDR) region encompassing nine antibiotic resistance genes and six IS26 insertion sequences. Tandem-repeat analysis and experimental validation demonstrated that blaKPC-2 amplification was indeed mediated by IS26, which was further experimentally shown to involve intricate genetic rearrangement. Such gene amplification arose dynamically under antibiotic stress and subsided upon antibiotic withdrawal. Instead of reducing the amplification of the IS26-flanked MDR region, drug combinations in vitro exacerbated it. Our study, thus, provides valuable insights into how dynamic gene amplification processes can precipitously transform resistance status and complicate diagnosis. IMPORTANCE Klebsiella pneumoniae carbapenemases (KPCs) are powerful β-lactamases that enable Gram-negative pathogens to destroy clinically important carbapenems in antibiotic therapies. In particular, KPC-2 is difficult to detect due to a lack of instrument sensitivity in regular laboratory screens, which leads to misdiagnosis and poor treatment outcomes. It remains unclear how blaKPC-2 rapidly induces exceedingly high-level resistance against carbapenems following the challenges of sublethal antibiotics. Here, we demonstrated that, under sublethal doses of antibiotics, insertion sequence IS26 mediated rapid amplification of multiple resistance determinants, including blaKPC-2 and a multiple drug resistance (MDR) region, which was accompanied by intricate genetic rearrangement.
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  • 文章类型: Journal Article
    The genome of the radiation-resistant bacterium Deinococcus geothermalis contains 19 types of insertion sequences (ISs), including 93 total transposases (Tpases) in 73 full-length ISs from the main chromosome and 2 mega plasmids. In this study, 68 ISs from the D. geothermalis genome were extracted to implicate the earlier genome before its mutation by transposition of ISs. The total size of eliminated ISs from genome was 78.85 kb. From these in silico corrections of mutation by the ISs, we have become aware of some bioinformatics factualness as follows: (1) can reassemble the disrupted genes if the exact IS region was eliminated, (2) can configure the schematic clustering of major DDE type Tpases, (3) can determine IS integration order across multiple hot spots, and (4) can compare genetic relativeness by the partial synteny analysis between D. geothermalis and Deinococcus strain S9. Recently, we found that several IS elements actively transferred to other genomic sites under hydrogen peroxide-induced oxidative stress conditions, resulting in the inactivation of functional genes. Therefore, the single species genome\'s mobilome study provides significant support to define bacterial genome plasticity and molecular evolution from past and present progressive transposition events.
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  • 文章类型: Journal Article
    Classical Bordetella species are primarily isolated from animals and humans causing asymptomatic infection to lethal pneumonia. However, isolation of these bacteria from any extra-host environmental niche has not been reported so far. Here, we have characterized the genomic plasticity and antibody response of Bordetella bronchiseptica strain HT200, isolated from a thermal spring. Genomic ANI value and SNPs-based phylogenetic tree suggest a divergent evolution of strain HT200 from a human-adapted lineage of B. bronchiseptica. Growth and survivability assay showed strain HT200 retained viability for more than 5 weeks in the filter-sterilized spring water. In addition, genes or loci encoding the Bordetella virulence factors such as DNT, ACT and LPS O-antigen were absent in strain HT200, while genes encoding other virulence factors were highly divergent. Phenotypically, strain HT200 was non-hemolytic and showed weak hemagglutination activity, but was able to colonize in the respiratory organs of mice. Further, both infection and vaccination with strain HT200 induced protective antibody response in mouse against challenge infection with virulent B. bronchiseptica strain RB50. In addition, genome of strain HT200 (DSM 26023) showed presence of accessory genes and operons encoding predicted metabolic functions pertinent to the ecological conditions of the thermal spring.
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