Shigellosis is a self-limiting disease that antibiotic therapy could decrease its complications and duration. However, sublethal levels of antibiotics, may lead to alteration in disease state, besides its role in the emergence of resistant variants. To understand this link, we investigated diversity of Shigella serogroups in children with diarrhea, diversity of S. flexneri serotypes, cytotoxic potential, resistance patterns to antibiotics, and alteration in transcriptional expression of main virulence genes in response to sub-inhibitory concentrations of azithromycin and ciprofloxacin. The most frequently isolated serogroups were S. sonnei (70.3%), followed by S. flexneri (29.1%) and S. boydii (0.6%). Ten serotypes were characterized among the S. flexneri isolates, including 2b, 1b, 2a, 1c, 4a, 3a, 3b, 6 and X and/or Xv. Antimicrobial susceptibility testing showed low frequency of multi-drug resistance phenotype among S. flexneri isolates with minimum inhibitory concentrations (MIC) of 0.5–64 and 0.25–8 µg/mL for azithromycin and ciprofloxacin, respectively. Gene expression analysis showed upregulation of icsA in serotype 4a after exposure with azithromycin, whereas other genes in the VirF pathway were downregulated, and downregulation of virB in serotypes 2a and 3a after exposure with ciprofloxacin, while upregulation of noted genes was detected. Alteration in transcription of key virulence genes of S. flexneri serotypes was shown in response to sublethal concentration of antibiotics. The detected incongruency in the extent of gene transcription proposed that diverse regulatory pathways are possibly mediating response to sub-MIC concentrations of antibiotics in S. flexneri.

中文翻译：

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不同福氏志贺菌血清型对亚抑制浓度阿奇霉素和环丙沙星的毒力基因表达谱分析

志贺氏菌病是一种自限性疾病，抗生素治疗可以减少其并发症和持续时间。然而，亚致死水平的抗生素可能会导致疾病状态的改变，除了它在抗性变体出现中的作用。为了理解这种联系，我们调查了腹泻儿童志贺氏菌血清群的多样性、弗氏链球菌血清型的多样性、细胞毒性潜力、对抗生素的耐药模式，以及主要毒力基因转录表达的改变，以响应亚抑制浓度的阿奇霉素和环丙沙星。最常分离的血清群是 S. sonnei (70.3%)，其次是 S. flexneri (29.1%) 和 S. boydii (0.6%)。在 S. flexneri 分离物中鉴定出 10 种血清型，包括 2b、1b、2a、1c、4a、3a、3b、6 和 X 和/或 Xv。抗菌药物敏感性试验显示，福氏链霉菌分离株中多重耐药表型的频率较低，阿奇霉素和环丙沙星的最低抑菌浓度 (MIC) 分别为 0.5-64 和 0.25-8 µg/mL。基因表达分析显示，暴露于阿奇霉素后血清型 4a 中 icsA 上调，而 VirF 通路中的其他基因下调，暴露于环丙沙星后血清型 2a 和 3a 中 virB 下调，同时检测到注意到基因的上调。S. flexneri 血清型的关键毒力基因的转录改变显示为对抗生素亚致死浓度的反应。