Sadredinamin Mehrzad, Shabani Mahdi, Karimi Abdollah, Sohrabi Mohammad-Reza, Karimi-Yazdi Mohammadmahdi, Ghalavand Zohreh, Alebouyeh Masoud
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Gut Pathog. 2022 Feb 22;14(1):10. doi: 10.1186/s13099-022-00483-3.
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.
志贺氏菌病是一种自限性疾病，抗生素治疗可减少其并发症并缩短病程。然而，除了在耐药变异株出现中所起的作用外，亚致死水平的抗生素可能会导致疾病状态改变。为了解这种联系，我们调查了腹泻儿童中志贺氏菌血清群的多样性、福氏志贺氏菌血清型的多样性、细胞毒性潜力、对抗生素的耐药模式，以及在亚抑制浓度的阿奇霉素和环丙沙星作用下主要毒力基因转录表达的变化。
最常分离出的血清群是宋内志贺氏菌（70.3%），其次是福氏志贺氏菌（29.1%）和鲍氏志贺氏菌（0.6%）。在福氏志贺氏菌分离株中鉴定出10种血清型，包括2b、1b、2a、1c、4a、3a、3b、6以及X和/或Xv。抗菌药敏试验显示，福氏志贺氏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 - 8μg/mL。基因表达分析显示，4a血清型在接触阿奇霉素后icsA上调，而VirF途径中的其他基因下调；2a和3a血清型在接触环丙沙星后virB下调，同时检测到上述基因上调。
福氏志贺氏菌血清型关键毒力基因的转录在亚致死浓度抗生素作用下出现改变。检测到的基因转录程度不一致表明，不同的调控途径可能介导福氏志贺氏菌对亚MIC浓度抗生素的反应。
