Dormancy in Acinetobacter baumannii and Klebsiella pneumoniae: Redefining Viable but Non-Culturable and Persister States

Bacterial dormancy is known to be associated with loss of culturability, leading to diagnosis failures. This misdiagnosis is significantly associated with Hospital Associated Infections- eight million annually and sepsis cases -eleven million annually. The realm of bacterial survival and antibiotic resistance, the mechanisms governing different dormancy states remain mysterious. Seeking to shed light on this enigma, our study delves into the intricate networks of gene expression and metabolic changes during dormancy transitions. Our findings unveil Same antibiotics induced early known as persistence and late known as VBNC dormancy states, distinguishable by the degree of dormancy attained. This transition into dormancy states involves halting cell growth and redirecting transcription and translation processes towards redirection of energy metabolism dynamics to maintain viability energy production through gluconeogenesis, respiration rate, and cell growth regulation and stress management TA system, PTM, diacylglycerol kinase, and glutathione S-transferases. The TA systems controls transcription during dormancy, while protein translation and Post Translational Modification are regulated by phosphatase kinase, acetylase, and deformylase enzymes. Which leads to significant metabolic transformations TCA cycle, amino acid, lipid nucleic acid and carbohydrate metabolism, utilizing internal resources for energy generation, through gluconeogenesis. The expression levels of toxins, kinases, and acetylases serve as markers for the degree of dormancy, heightened expression indicates a deeper dormant state. Though TA system and protein regulation have been shown to be associated with dormancy, the detailed modus operandi of energy metabolism dynamics alteration remains elusive. Present study demonstrated TA system and PTM drive alteration of energy metabolism in Gram- negative bacteria, to define various level of dormancy, early and late. Although these reversible changes inhibit bacterial growth, restoration of these changes also demonstrated after resuscitation. Our study endeavors to unravel the intricate connections within this narrative, enhancing our understanding of bacterial dormancy and its implications in antibiotic resistance.