Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India.
Department of Veterinary Physiology & Biochemistry, College of Veterinary Sciences & A.H., Central Agricultural University, Selesih, Aizawl, Mizoram, 796014, India.
Microb Pathog. 2022 Jul;168:105591. doi: 10.1016/j.micpath.2022.105591. Epub 2022 May 21.
How recoding of fnr, an anaerobic regulatory gene, affects pathogenicity related parameters of Salmonella Typhimurium (STM).
The fnr gene was recoded by substituting all of it's codons with synonymous rare codons of STM. Recoding fnr gene severely reduced the ability of the recoded mutant to compete with wild strain under nutrient depletion condition. Mutants were also less motile than the wild strain and their biofilm forming ability was significantly decreased as compared to wild strain. The recoded strain showed significant reduced survival within murine macrophages (RAW264.7) and monocyte derived macrophage of poultry origin. The colonisation ability of recoded mutant in liver and spleen of mice on day 5 of post infection was significantly reduced. The recoded strain exhibited significant reduction in faecal shedding on day 1 and 5 after infection.
Our study showed that recoding the anaerobic regulator fnr of STM significantly compromised its growth, decreased motility, biofilm forming ability and survival within macrophages. Further, the recoded fnr strain showed reduced colonisation ability and faecal shedding in mice. Thus, these findings highlight that recoding the global anaerobic regulator fnr of Salmonella Typhimurium attenuates its pathogenicity.
fnr 是一种厌氧调控基因，研究其重编码如何影响鼠伤寒沙门氏菌（STM）的致病性相关参数。
用 STM 的同义稀有密码子替代 fnr 基因的所有密码子，对 fnr 基因进行重编码。重编码 fnr 基因严重降低了重组突变体在营养缺乏条件下与野生株竞争的能力。与野生株相比，突变体的运动能力也较弱，生物膜形成能力显著降低。与野生株相比，重组菌株在鼠源巨噬细胞（RAW264.7）和禽源单核细胞衍生巨噬细胞中的存活率显著降低。重组突变体在感染后第 5 天在小鼠肝脏和脾脏中的定植能力显著降低。感染后第 1 天和第 5 天，重组菌株的粪便脱落量显著减少。
本研究表明，重编码 STM 的厌氧调控因子 fnr 显著削弱了其生长、运动能力、生物膜形成能力和巨噬细胞内的生存能力。此外，重编码的 fnr 菌株在小鼠中的定植能力和粪便脱落量也减少。因此，这些发现强调了重编码鼠伤寒沙门氏菌的全局厌氧调控因子 fnr 可减弱其致病性。
