Division of Infectious Diseases, Department of Pediatrics, McGovern Medical School, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
Department of Infectious Diseases, Division of Internal Medicine, The University of Texas MD Anderson Cancer Centergrid.240145.6, Houston, Texas, USA.
Infect Immun. 2022 Aug 18;90(8):e0008022. doi: 10.1128/iai.00080-22. Epub 2022 Aug 1.
Antimicrobial resistance-encoding mobile genetic elements (MGEs) may contribute to the disease potential of bacterial pathogens. We previously described the association of Group A Streptococcus (GAS) derived from invasive disease with increasingly frequent antimicrobial resistance (AMR). We hypothesized that a 65-kb AMR-encoding MGE (ICESpyM92), highly conserved among closely related emergent invasive GAS, contributes to GAS disease potential. Here, we provide evidence that a combination of ICESpyM92- and core genome-dependent differential gene expression (DGE) contributes to invasive disease phenotypes of emergent GAS. Using isogenic ICESpyM92 mutants generated in distinct genomic backgrounds, we determined the presence of ICESpyM92 enhances GAS virulence in a mouse subcutaneous infection model. Measurement of and DGE indicates ICESpyM92 influences GAS global gene expression in a background-dependent manner. Our study links virulence and AMR on a unique MGE via MGE-related DGE and highlights the importance of investigating associations between AMR-encoding MGEs and pathogenicity.
携带抗菌药物耐药性的可移动遗传元件（MGE）可能会增加细菌病原体的疾病潜力。我们之前描述了源自侵袭性疾病的 A 组链球菌（GAS）与日益频繁的抗菌药物耐药性（AMR）之间的关联。我们假设，在密切相关的新兴侵袭性 GAS 中高度保守的 65kb 编码 AMR 的 MGE（ICESpyM92）有助于 GAS 的疾病潜力。在这里，我们提供的证据表明，ICESpyM92 和核心基因组依赖性差异基因表达（DGE）的组合有助于新兴 GAS 的侵袭性疾病表型。使用在不同基因组背景下生成的同源 ICESpyM92 突变体，我们确定了 ICESpyM92 的存在增强了 GAS 在小鼠皮下感染模型中的毒力。ICESpyM92 影响 GAS 全局基因表达的方式存在背景依赖性。我们的研究通过 MGE 相关的 DGE 将毒力和 AMR 联系在一个独特的 MGE 上，强调了研究 AMR 编码 MGE 与致病性之间关联的重要性。
