PDF(Pubmed)
Abstract：
UNASSIGNED: Mycoplasma hominis (M. hominis) belongs to the class Mollicutes, characterized by a very small genome size, reduction of metabolic pathways, including transcription factors, and the absence of a cell wall. Despite this, they adapt well not only to specific niches within the host organism but can also spread throughout the body, colonizing various organs and tissues. The adaptation mechanisms of M. hominis, as well as their regulatory pathways, are poorly understood. It is known that, when adapting to adverse conditions, Mycoplasmas can undergo phenotypic switches that may persist for several generations.
UNASSIGNED: To investigate the adaptive properties of M. hominis related to survival in the host, we conducted a comparative phenotypic and proteogenomic analysis of eight clinical isolates of M. hominis obtained from patients with urogenital infections and the laboratory strain H-34.
UNASSIGNED: We have shown that clinical isolates differ in phenotypic features from the laboratory strain, form biofilms more effectively and show resistance to ofloxacin. The comparative proteogenomic analysis revealed that, unlike the laboratory strain, the clinical isolates possess several features related to stress survival: they switch carbon metabolism, activating the energetically least advantageous pathway of nucleoside utilization, which allows slowing down cellular processes and transitioning to a starvation state; they reconfigure the repertoire of membrane proteins; they have integrative conjugative elements in their genomes, which are key mediators of horizontal gene transfer. The upregulation of the methylating subunit of the restriction-modification (RM) system type I and the additional components of RM systems found in clinical isolates suggest that DNA methylation may play a role in regulating the adaptation mechanisms of M. hominis in the host organism. It has been shown that based on the proteogenomic profile, namely the genome sequence, protein content, composition of the RM systems and additional subunits HsdM, HsdS and HsdR, composition and number of transposable elements, as well as the sequence of the main variable antigen Vaa, we can divide clinical isolates into two phenotypes: typical colonies (TC), which have a high growth rate, and atypical (aTC) mini-colonies, which have a slow growth rate and exhibit properties similar to persisters.
UNASSIGNED: We believe that the key mechanism of adaptation of M. hominis in the host is phenotypic restructuring, leading to a slowing down cellular processes and the formation of small atypical colonies. This is due to a switch in carbon metabolism and activation the pathway of nucleoside utilization. We hypothesize that DNA methylation may play a role in regulating this switch.
UNASSIGNED: To investigate the adaptive properties of M. hominis related to survival in the host, we conducted a comparative phenotypic and proteogenomic analysis of eight clinical isolates of M. hominis obtained from patients with urogenital infections and the laboratory strain H-34.
UNASSIGNED: We have shown that clinical isolates differ in phenotypic features from the laboratory strain, form biofilms more effectively and show resistance to ofloxacin. The comparative proteogenomic analysis revealed that, unlike the laboratory strain, the clinical isolates possess several features related to stress survival: they switch carbon metabolism, activating the energetically least advantageous pathway of nucleoside utilization, which allows slowing down cellular processes and transitioning to a starvation state; they reconfigure the repertoire of membrane proteins; they have integrative conjugative elements in their genomes, which are key mediators of horizontal gene transfer. The upregulation of the methylating subunit of the restriction-modification (RM) system type I and the additional components of RM systems found in clinical isolates suggest that DNA methylation may play a role in regulating the adaptation mechanisms of M. hominis in the host organism. It has been shown that based on the proteogenomic profile, namely the genome sequence, protein content, composition of the RM systems and additional subunits HsdM, HsdS and HsdR, composition and number of transposable elements, as well as the sequence of the main variable antigen Vaa, we can divide clinical isolates into two phenotypes: typical colonies (TC), which have a high growth rate, and atypical (aTC) mini-colonies, which have a slow growth rate and exhibit properties similar to persisters.
UNASSIGNED: We believe that the key mechanism of adaptation of M. hominis in the host is phenotypic restructuring, leading to a slowing down cellular processes and the formation of small atypical colonies. This is due to a switch in carbon metabolism and activation the pathway of nucleoside utilization. We hypothesize that DNA methylation may play a role in regulating this switch.
摘要：
■人型支原体(M.hominis)属于Mollicutes类，以非常小的基因组大小为特征，减少代谢途径，包括转录因子，没有细胞壁.尽管如此,它们不仅能很好地适应宿主生物体内的特定生态位，而且还能在全身传播，定殖各种器官和组织。人马的适应机制，以及他们的监管途径，知之甚少。众所周知,当适应不利条件时，支原体可以经历可能持续几代的表型转换。
■为了研究与宿主生存相关的人型支原体的适应性，我们对来自泌尿生殖道感染患者的8株人型支原体临床分离株和实验室菌株H-34进行了表型和蛋白质基因组比较分析.
■我们已经表明，临床分离株的表型特征与实验室菌株不同，更有效地形成生物膜并显示出对氧氟沙星的抗性。比较蛋白质基因组分析显示，与实验室菌株不同，临床分离株具有与应激存活相关的几个特征：它们转换碳代谢，激活核苷利用的能量上最不利的途径，这允许减慢细胞过程并过渡到饥饿状态；它们重新配置膜蛋白的库；它们在基因组中具有整合的共轭元件，它们是水平基因转移的关键媒介。I型限制性修饰（RM）系统的甲基化亚基的上调以及在临床分离物中发现的RM系统的其他成分表明，DNA甲基化可能在调节宿主中的人型支原体的适应机制中起作用。生物体。已经表明，基于蛋白质基因组谱，即基因组序列，蛋白质含量，RM系统和附加亚基HsdM的组成，HsdS和HsdR,转座因子的组成和数量，以及主要可变抗原Vaa的序列，我们可以将临床分离株分为两种表型：典型菌落（TC），增长率很高，和非典型（aTC）小菌落，其生长速度缓慢，表现出与持久性相似的特性。
■我们认为人源支原体在宿主中适应的关键机制是表型重组，导致细胞过程减慢并形成小的非典型菌落。这是由于碳代谢的转换和核苷利用途径的激活。我们假设DNA甲基化可能在调节这种开关中起作用。
■为了研究与宿主生存相关的人型支原体的适应性，我们对来自泌尿生殖道感染患者的8株人型支原体临床分离株和实验室菌株H-34进行了表型和蛋白质基因组比较分析.
■我们已经表明，临床分离株的表型特征与实验室菌株不同，更有效地形成生物膜并显示出对氧氟沙星的抗性。比较蛋白质基因组分析显示，与实验室菌株不同，临床分离株具有与应激存活相关的几个特征：它们转换碳代谢，激活核苷利用的能量上最不利的途径，这允许减慢细胞过程并过渡到饥饿状态；它们重新配置膜蛋白的库；它们在基因组中具有整合的共轭元件，它们是水平基因转移的关键媒介。I型限制性修饰（RM）系统的甲基化亚基的上调以及在临床分离物中发现的RM系统的其他成分表明，DNA甲基化可能在调节宿主中的人型支原体的适应机制中起作用。生物体。已经表明，基于蛋白质基因组谱，即基因组序列，蛋白质含量，RM系统和附加亚基HsdM的组成，HsdS和HsdR,转座因子的组成和数量，以及主要可变抗原Vaa的序列，我们可以将临床分离株分为两种表型：典型菌落（TC），增长率很高，和非典型（aTC）小菌落，其生长速度缓慢，表现出与持久性相似的特性。
■我们认为人源支原体在宿主中适应的关键机制是表型重组，导致细胞过程减慢并形成小的非典型菌落。这是由于碳代谢的转换和核苷利用途径的激活。我们假设DNA甲基化可能在调节这种开关中起作用。
