Streptococcus pneumoniae transformation occurs within a short competence window, during which the alternative sigma factor X (SigX) is activated to orchestrate the expression of genes allowing extracellular DNA uptake and recombination. Importantly, antibiotic stress promotes transcriptional changes that may affect more than 20% of the S. pneumoniae genome, including competence genes. These can be activated or repressed, depending on the antibiotic agent. For most antibiotics, however, it remains unknown whether transcriptional effects on competence translate into altered transformability. Here we investigate the effect of antibiotic subinhibitory concentrations on sigX expression using a luciferase reporter, and correlate for the first time with transformation kinetics. Induction of sigX expression by ciprofloxacin and novobiocin correlated with increased and prolonged transformability in S. pneumoniae. The prolonged effect of ciprofloxacin on competence and transformation was also observed in the streptococcal relatives Streptococcus mitis and Streptococcus mutans. In contrast, tetracycline and erythromycin, which induced S. pneumoniae sigX expression, had either an inhibitory or a nonsignificant effect on transformation, whereas streptomycin and the β‐lactam ampicillin, inhibited both sigX expression and transformation. Thus, the results show that antibiotics may vary in their effects on competence, ranging from inhibitory to stimulatory effects, and that responses affecting transcription of sigX do not always correlate with the transformation outcomes. Antibiotics that increase or decrease transformation are of particular clinical relevance, as they may alter the ability of S. pneumoniae to escape vaccines and antibiotics.

中文翻译：

---

抗生素改变了链球菌自然转化的能力范围。

肺炎链球菌转化发生在很短的能力窗口内，在此过程中，替代的sigma因子X（SigX）被激活以协调基因表达，从而允许细胞外DNA吸收和重组。重要的是，抗生素应激会促进可能影响超过20％的肺炎链球菌基因组（包括能力基因）的转录变化。它们可以被激活或抑制，具体取决于抗生素。但是，对于大多数抗生素而言，转录对能力的影响是否会转化为可转化的性仍是未知的。在这里，我们研究了抗生素亚抑制浓度对sigX的影响荧光素酶报道基因表达，并首次与转化动力学相关。环丙沙星和新霉素诱导sigX表达与肺炎链球菌转化率增加和延长有关。在链球菌的亲属链球菌炎和变形链球菌中也观察到环丙沙星对能力和转化的延长作用。相反，诱导肺炎链球菌sigX表达的四环素和红霉素对转化具有抑制作用或无显着作用，而链霉素和β-内酰胺氨苄青霉素则抑制sigX。表达和转化。因此，结果表明，抗生素对能力的影响可能有所不同，范围从抑制作用到刺激作用，而且影响sigX转录的反应并不总是与转化结果相关。增加或减少转化的抗生素具有特殊的临床意义，因为它们可能会改变肺炎链球菌逃脱疫苗和抗生素的能力。