Bao Yun-Juan, Liang Zhong, Mayfield Jeffrey A, Donahue Deborah L, Carothers Katelyn E, Lee Shaun W, Ploplis Victoria A, Castellino Francis J
W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA.
W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
J Bacteriol. 2016 May 27;198(12):1712-24. doi: 10.1128/JB.01019-15. Print 2016 Jun 15.
The genome of an invasive skin-tropic strain (AP53) of serotype M53 group A Streptococcus pyogenes (GAS) is composed of a circular chromosome of 1,860,554 bp and carries genetic markers for infection at skin locales, viz, emm gene family pattern D and FCT type 3. Through genome-scale comparisons of AP53 with other GAS genomes, we identified 596 candidate single-nucleotide polymorphisms (SNPs) that reveal a potential genetic basis for skin tropism. The genome of AP53 differed by ∼30 point mutations from a noninvasive pattern D serotype M53 strain (Alab49), 4 of which are located in virulence genes. One pseudogene, yielding an inactive sensor kinase (CovS(-)) of the two-component transcriptional regulator CovRS, a major determinant for invasiveness, severely attenuated the expression of the secreted cysteine protease SpeB and enhanced the expression of the hyaluronic acid capsule compared to the isogenic noninvasive AP53/CovS(+) strain. The collagen-binding protein transcript sclB differed in the number of 5'-pentanucleotide repeats in the signal peptides of AP53 and Alab49 (9 versus 15), translating into different lengths of their signal peptides, which nonetheless maintained a full-length translatable coding frame. Furthermore, GAS strain AP53 acquired two phages that are absent in Alab49. One such phage (ΦAP53.2) contains the known virulence factor superantigen exotoxin gene tandem speK-slaA Overall, we conclude that this bacterium has evolved in multiple ways, including mutational variations of regulatory genes, short-tandem-repeat polymorphisms, large-scale genomic alterations, and acquisition of phages, all of which may be involved in shaping the adaptation of GAS in specific infectious environments and contribute to its enhanced virulence.
Infectious strains of S. pyogenes (GAS) are classified by their serotypes, relating to the surface M protein, the emm-like subfamily pattern, and their tropicity toward the nasopharynx and/or skin. It is generally agreed that M proteins from pattern D strains, which also directly bind human host plasminogen, are skin tropic. We have sequenced and characterized the genome of an invasive pattern D GAS strain (AP53) in comparison to a very similar strain (Alab49) that is noninvasive and developed a genomic rationale as to possible reasons for the skin tropicity of these two strains and the greater invasiveness of AP53.
A群化脓性链球菌（GAS）M53血清型的一种侵袭性皮肤嗜性菌株（AP53）的基因组由一条1,860,554 bp的环状染色体组成，并携带皮肤部位感染的遗传标记，即emm基因家族模式D和FCT 3型。通过对AP53与其他GAS基因组进行全基因组规模比较，我们鉴定出596个候选单核苷酸多态性（SNP），揭示了皮肤嗜性的潜在遗传基础。AP53的基因组与非侵袭性模式D血清型M53菌株（Alab49）相比有~30个点突变，其中4个位于毒力基因中。一个假基因产生了双组分转录调节因子CovRS的无活性传感器激酶（CovS（-）），CovRS是侵袭性的主要决定因素，与同基因的非侵袭性AP53/CovS（+）菌株相比，它严重减弱了分泌型半胱氨酸蛋白酶SpeB的表达，并增强了透明质酸荚膜的表达。胶原蛋白结合蛋白转录本sclB在AP53和Alab49信号肽中的5'-五核苷酸重复数不同（分别为9个和15个），导致它们信号肽长度不同，但仍保持全长可翻译编码框。此外，GAS菌株AP53获得了两个Alab49中不存在的噬菌体。其中一个噬菌体（ΦAP53.2）包含已知的毒力因子超抗原外毒素基因串联speK-slaA。总体而言，我们得出结论，这种细菌已经以多种方式进化，包括调节基因的突变变异、短串联重复多态性、大规模基因组改变和噬菌体获得，所有这些都可能参与塑造GAS在特定感染环境中的适应性并促进其毒力增强。
化脓性链球菌（GAS）的感染菌株按血清型分类，与表面M蛋白、emm样亚家族模式以及它们对鼻咽和/或皮肤的嗜性有关。人们普遍认为，模式D菌株的M蛋白也直接结合人类宿主纤溶酶原，具有皮肤嗜性。我们对一种侵袭性模式D GAS菌株（AP53）的基因组进行了测序和表征，并与一种非常相似的非侵袭性菌株（Alab49）进行了比较，从而对这两种菌株的皮肤嗜性以及AP53更强的侵袭性的可能原因建立了基因组学依据。
