Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.
Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.
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DOI：
10.1371/journal.pone.0093970
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Citti C
中科院分区：
文献类型：
--
作者：
Baranowski E;Bergonier D;Sagné E;Hygonenq MC;Ronsin P;Berthelot X;Citti C
人们对支原体感染致病过程的机制知之甚少，主要是因为与经典细菌毒力因子的序列相似性有限。最近，反刍动物病原体无乳支原体中的大规模转座子诱变鉴定出 NIF 位点，包括 nifS 和 nifU，对于细胞培养中支原体的生长至关重要，而在无菌培养基中则是可有可无的。为了评估该基因座在体内的重要性，在自然宿主中进行实验感染后测试了两种敲除突变体的感染性。在该模型中，即使以低剂量接种，亲本 PG2 菌株也能够在哺乳期母羊中建立全身感染，在淋巴结和乳腺等身体各个部位定殖。在这些感染 PG2 的母羊中，我们在感染过程中观察到 (i) 特异性抗体反应的发展和 (ii) 无乳分枝杆菌表面可变蛋白 (Vpma) 表达的动态变化，其中多种 Vpma 谱在同一动物中共存。相比之下，尽管有一个敏感的模型，但没有一个敲除突变体能够存活并定植于宿主。接种动物中不存在 IgG 反应进一步支持了这两种突变体的极端无毒力表型。 NIF 位点的确切作用仍有待阐明，但这些数据表明，它在无乳支原体以及很可能其他致病性支原体物种的感染过程中发挥着关键作用，因为许多支原体携带密切相关的同源物。
Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i) the development of a specific antibody response and (ii) dynamic changes in expression of M. agalactiae surface variable proteins (Vpma), with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.
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影响因子：
--
作者：
MACOWAN, KJ;BRAND, TF;HUNTER, AR
通讯作者：
HUNTER, AR
影响因子：
3.7
作者：
Cacciotto C;Addis MF;Coradduzza E;Carcangiu L;Nuvoli AM;Tore G;Dore GM;Pagnozzi D;Uzzau S;Chessa B;Pittau M;Alberti A
通讯作者：
Alberti A
影响因子：
3.1
作者：
Balasubramanian, Sowmya;Kannan, T. R.;Baseman, Joel B.
通讯作者：
Baseman, Joel B.
影响因子：
3.1
作者：
Baranowski, Eric;Guiral, Sebastien;Citti, Christine
通讯作者：
Citti, Christine
影响因子：
2.8
作者：
Marenda, MS;Sagné, E;Citti, C
通讯作者：
Citti, C