Gdowicz-Kłosok Agnieszka, Krześniak Małgorzata, Łasut-Szyszka Barbara, Butkiewicz Dorota, Rusin Marek
Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-101 Gliwice, Poland.
Int J Mol Sci. 2025 May 6;26(9):4416. doi: 10.3390/ijms26094416.
The p53 tumor suppressor is best known for controlling the cell cycle, apoptosis, DNA repair, and metabolism, but it also regulates immunity and is able to impede the live cycle of viruses. For this reason, these infectious agents encode proteins which inactivate p53. However, what is less known is that p53 can also be inactivated by human pathogenic bacteria. It is probably not due to collateral damage, but specific targeting, because p53 could interfere with their multiplication. The mechanisms of the antibacterial activity of p53 are poorly known. However, they can be inferred from the results of high-throughput studies, which have identified more than a thousand p53-activated genes. As it turns out, many of these genes code proteins which have proven or plausible antibacterial functions like the efficient detection of bacteria by pattern recognition receptors, the induction of pro-inflammatory pyroptosis, the recruitment of immune cells, direct bactericidal activity, and the presentation of bacterial metabolites to lymphocytes. Probably there are more antibacterial, p53-regulated functions which were overlooked because laboratory animals are kept in sterile conditions. In this review, we present the outlines of some intriguing antibacterial mechanisms of p53 which await further exploration. Definitely, this area of research deserves more attention, especially in light of the appearance of antibiotic-resistant bacterial strains.
p53肿瘤抑制因子最为人所知的是其对细胞周期、细胞凋亡、DNA修复和代谢的调控作用，但它也调节免疫，并且能够阻碍病毒的生命周期。因此，这些感染因子编码使p53失活的蛋白质。然而，鲜为人知的是，p53也会被人类病原菌灭活。这可能并非附带损害，而是特异性靶向作用，因为p53可能会干扰它们的繁殖。p53抗菌活性的机制尚不清楚。不过，可以从高通量研究的结果中推断出来，这些研究已经鉴定出一千多个p53激活基因。事实证明，其中许多基因编码的蛋白质具有已被证实或可能的抗菌功能，如通过模式识别受体有效检测细菌、诱导促炎性细胞焦亡、募集免疫细胞、直接杀菌活性以及将细菌代谢产物呈递给淋巴细胞。可能还有更多p53调节的抗菌功能被忽视了，因为实验动物是在无菌条件下饲养的。在这篇综述中，我们概述了p53一些有趣的抗菌机制，有待进一步探索。当然，这一研究领域值得更多关注，尤其是鉴于抗生素耐药菌株的出现。
