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PatA
Microbiology Spectrum · 2023 ·Vol. 11 ·期 3 · IF 3.7

PatA Regulates Isoniazid Resistance by Mediating Mycolic Acid Synthesis and Controls Biofilm Formation by Affecting Lipid Synthesis in Mycobacteria

Kun Wang,Yimin Deng,Xujie Cui,Mengli Chen,Yanzhe Ou,Danting Li,Minhao Guo,Weihui Li

Lipids are prominent components of the mycobacterial cell wall, and they play critical roles not only in maintaining biofilm formation but also in resisting environmental stress, including drug resistance. However, information regarding the mechanism mediating mycobacterial lipid synthesis remains limited. PatA is a membrane-associated acyltransferase and synthesizes phosphatidyl-myo-inositol mannosides (PIMs) in mycobacteria. Here, we found that PatA could regulate the synthesis of lipids (except mycolic acids) to maintain biofilm formation and environmental stress resistance in Mycolicibacterium smegmatis. Interestingly, the deletion of patA significantly enhanced isoniazid (INH) resistance in M. smegmatis, although it reduced bacterial biofilm formation. This might be due to the fact that the patA deletion promoted the synthesis of mycolic acids through an unknown synthesis pathway other than the reported fatty acid synthase (FAS) pathway, which could effectively counteract the inhibition by INH of mycolic acid synthesis in mycobacteria. Furthermore, the amino acid sequences and physiological functions of PatA were highly conserved in mycobacteria. Therefore, we found a mycolic acid synthesis pathway regulated by PatA in mycobacteria. In addition, PatA also affected biofilm formation and environmental stress resistance by regulating the synthesis of lipids (except mycolic acids) in mycobacteria.IMPORTANCE Tuberculosis, caused by Mycobacterium tuberculosis, leads to a large number of human deaths every year. This is so serious, which is due mainly to the drug resistance of mycobacteria. INH kills M. tuberculosis by inhibiting the synthesis of mycolic acids, which are synthesized by the FAS pathway. However, whether there is another mycolic acid synthesis pathway is unknown. In this study, we found a PatA-mediated mycolic acid synthesis pathway that led to INH resistance of in patA-deleted mutant. In addition, we first report the regulatory effect of PatA on mycobacterial biofilm formation, which could affect the bacterial response to environmental stress. Our findings represent a new model for regulating biofilm formation by mycobacteria. More importantly, the discovery of the PatA-mediated mycolic acid synthesis pathway indicates that the study of mycobacterial lipids has entered a new stage, and the enzymes might be new targets of antituberculosis drugs.

研究领域: 微生物学 · 分子生物学 · 传染病学 · 细菌生理学 · 抗生素耐药性
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2025 · IF 4.7

Enhanced electrochemical immunosensor utilizing pATA/AuNPs for sensitive detection of the leukemia-associated biomarker CD123 in bone marrow supernatant

Xin Li,Qing Wang,Chun-Rong Qin,Ai-Lin Liu,Yong Chen

Background: Cluster of differentiation 123 (CD123) prominently overexpress in various hematological malignancies and plays a crucial role in diagnosis and prognosis of leukemia. Clinical studies have demonstrated that cell-free CD123 levels also significantly influence leukemia immunotherapy outcomes. The development of novel electrochemical immunosensors addresses the need for point-of-care detection tools, thereby facilitating advancements in clinical monitoring technologies. Methods: This study presented a practical electrochemical immunosensor constructed using sandwich strategy for CD123 detection based on the modification of gold nanoparticles and poly(2-aminoterephthalic acid). Common proteins and tumor-related biomarkers found in human were selected as interference factors to evaluate the detection specificity of the electrochemical immunosensor. Further, the electrochemical immunosensor was utilized to directly detect CD123 in bone marrow supernatant from leukemia patients. Results: The constructed electrochemical immunosensor exhibited good linearity for CD123 detection over a range of 0.02 to 2.5 µg/mL, with a detection limit of 12.8 ng/mL, alongside satisfactory specificity and repeatability. Furthermore, the immunosensor was successfully employed to detect CD123 levels in the bone marrow supernatant of leukemia patients, demonstrating results that were highly consistent with those obtained via ELISA. Conclusions: The developed approach is anticipated to provide robust technical support for the long-term monitoring of leukemia patients during their diagnosis and treatment.

研究领域: 医学诊断 · 生物传感技术 · 肿瘤学
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POSTHARVEST BIOLOGY AND TECHNOLOGY · 2023 · IF 7

Blue LED light treatment inhibits virulence and patulin biosynthesis in Penicillium expansum

Ruiyu Zhu,Weilun Wang,Zisheng Luo,Haiyan Lin,Yong Li,Weiqiang Lu,Zimu Xu,Chenggang Cai,Shuheng Hu

Blue light-emitting diode (LED) light has been considered to influence the growth, quality, and preservation of certain fruit and vegetable. However, the blue LED light impact on apple postharvest blue mold remains elusive. In this study, the influence of blue LED light on Penicillium expansum virulence and patulin secretion was investigated in vitro and in vivo, as well as on the apple quality. The growth of P. expansum was inhibited by blue LED light via changes in mycelium morphology changes, cell membrane integrity, and potential mitochondrial membrane destruction, thereby causing reactive oxygen species accumulation, oxidative stress , and mitochondrial dysfunction. Furthermore, the expression level of LaeA relevant to the pathogenicity of P. expansum , was down-regulated. Specifically, the patulin production of P. expansum was inhibited via expression down-regulation of the patulin biosynthesis-related genes PatA , PatE , and PatN rather than direct degradation by the blue LED light treatment. Additionally, no significant effects on the fruit quality were observed when the light intensity was lower than 120 μmol m -2 s -1 . In summary, blue LED light treatment has the potential for a low-cost, safe, and non-chemical approach to control apple postharvest decay.

研究领域: 食品科学 · 微生物学 · 植物病理学
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