Accumulating evidence indicates that bacterial metabolism plays an important role in virulence. Acetyl phosphate (AcP), the high-energy intermediate of the phosphotransacetylase-acetate kinase pathway, is the major acetyl donor in
E. coli
. PhoP is an essential transcription factor for bacterial virulence. Here, we show in
Salmonella typhimurium
that PhoP is non-enzymatically acetylated by AcP, which modifies its transcriptional activity, demonstrating that the acetylation of Lysine 102 (K102) is dependent on the intracellular AcP. The acetylation level of K102 decreases under PhoP-activating conditions including low magnesium, acid stress or following phagocytosis. Notably,
in vitro
assays show that K102 acetylation affects PhoP phosphorylation and inhibits its transcriptional activity. Both cell and mouse models show that K102 is critical to
Salmonella
virulence, and suggest acetylation is involved in regulating PhoP activity. Together, the current study highlights the importance of the metabolism in bacterial virulence, and shows AcP might be a key mediator.
Objective: To investigate the clinical therapeutic outcomes and neck node control of a pretreatment neck dissection in the chemoradiation protocol of organ preservation for N2-N3 of supraglottic and hypopharyngeal carcinoma. Methods: Forty-six patients (group A) with untreated N2 or N3 squamous cell carcinoma of the supraglottis or hypopharynx underwent pretreatment neck dissection in a chemoradiation protocol, while 39 patients (group B) did not undergo pretreatment neck dissection in a chemoradiation protocol. Salvage surgeries were used for local or cervical node residual tumor or recurrence after chemoradiotherapy. Results: In group A, the mean time between neck dissection and chemoradiation was 21 days (range 15-29). Only 3 patients (6.5%) experienced wound complications. A ‘boost' of radiation of 12 Gy was delivered after 33 neck dissections (64.8%) in patients with extracapsular spread. The Kaplan-Meier 5-year overall survival rate was 42.5%. The 5-year overall survival rate and disease-specific survival rate in group A was 42.5 and 46.4%. The rate of neck node control in group A was better than that in group B (86.3 vs. 65.9%, p = 0.02). Conclusions: Pretreatment neck dissection in a chemoradiation protocol for supraglottic or hypopharyngeal carcinoma showed low complication rates, no delay for radiation, optimal radiation doses, and a high nodal disease control.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.