作者:
Jiang, Zhulin;Li, Shuihong*;Zhu, Cuiming*;Zhou, Runjie;Leung, Polly H. M.
期刊:
Pathogens,2021年10(2):119- ISSN:2076-0817
通讯作者:
Li, Shuihong;Zhu, Cuiming
作者机构:
[Jiang, Zhulin; Li, Shuihong; Zhu, CM; Zhu, Cuiming; Zhou, Runjie] Univ South China, Hengyang Med Coll, Inst Pathogen Biol, Hengyang 421001, Peoples R China.;[Leung, Polly H. M.] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong 999077, Peoples R China.
通讯机构:
[Li, SH; Zhu, CM] U;Univ South China, Hengyang Med Coll, Inst Pathogen Biol, Hengyang 421001, Peoples R China.
摘要:
Mycoplasma pneumoniae is a major causative agent of community-acquired pneumonia which can lead to both acute upper and lower respiratory tract inflammation, and extrapulmonary syndromes. Refractory pneumonia caused by M. pneumonia can be life-threatening, especially in infants and the elderly. Here, based on a comprehensive review of the scientific literature related to the respective area, we summarize the virulence factors of M. pneumoniae and the major pathogenic mechanisms mediated by the pathogen: adhesion to host cells, direct cytotoxicity against host cells, inflammatory response-induced immune injury, and immune evasion. The increasing rate of macrolide-resistant strains and the harmful side effects of other sensitive antibiotics (e.g., respiratory quinolones and tetracyclines) in young children make it difficult to treat, and increase the health risk or re-infections. Hence, there is an urgent need for development of an effective vaccine to prevent M. pneumoniae infections in children. Various types of M. pneumoniae vaccines have been reported, including whole-cell vaccines (inactivated and live-attenuated vaccines), subunit vaccines (involving M. pneumoniae protein P1, protein P30, protein P116 and CARDS toxin) and DNA vaccines. This narrative review summarizes the key pathogenic mechanisms underlying M. pneumoniae infection and highlights the relevant vaccines that have been developed and their reported effectiveness.
作者机构:
[朱翠明; Zeng W.; 游晓星; 余斓; 丁伟艳; 陈列松] Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, University of South China, Hengyang, 421001, China;[黄立军] Hunan Provincial Graduate Training Innovation Base, South China University-Nanyue Biopharming Corporation, Ltd., Hengyang, 421001, China
通讯机构:
[Zhu, C.] H;Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, University of South China, Hengyang, China
摘要:
In the past few years, we have witnessed great development and application potential of various up-conversion luminescent nanoparticles (UCNPs) in the nanomedicine field. Based on the unique luminescent mechanism of UCNPs and the distinguishable features of cancer biomarkers and the microenvironment, an increasing number of smart UCNPs nanoprobes have been designed and widely applied to molecular imaging, cancer diagnosis, and treatment. Considerable technological success has been achieved, but the main obstacles to oncology nanomedicine is becoming an incomplete understanding of nano-bio interactions, the challenges regarding chemistry manufacturing and controls required for clinical translation and so on. This review highlights the progress of the design principles, synthesis and surface functionalization preparation, underlying applications and challenges of UCNPs-based probes for cancer bioimaging, diagnosis and treatment that capitalize on our growing understanding of tumor biology and smart nano-devices for accelerating the commercialization of UCNPs.
通讯机构:
[Zeng, Yanhua] U;[Zeng, Yanhua] H;Univ South China, Inst Pathogen Biol, Hengyang Med Coll, 28 West Changsheng Rd,Zhengxiang Dist St, Hengyang 421001, Hunan, Peoples R China.;Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang 421001, Hunan, Peoples R China.
关键词:
Mycoplasma genitalium;Adhesin protein;Phage display random peptide library;Binding peptides
摘要:
Mycoplasma genitalium protein of adhesion (MgPa) is a vital membrane protein, which plays an important role in mediating the adhesion and infection of M. genitalium to host cells. This study aims to screen and identify the specific binding peptides of MgPa. Phage display with random 12-mer and 7-mer peptide libraries was carried out to obtain the phages specifically bound to recombinant MgPa (rMgPa). Two concensus core sequences, i.e. VHWDFRQWWQPS and DWSSWVH(Y)RDPQT(S), were identified from the 12-mer peptide library and one consistent core sequence, i.e. HYIDFRW, was obtained from the 7-mer peptide library. Representative phages containing any of the three sequences could specifically bind to rMgPa. The three peptides shared high homology with human antigens as showed by BLAST analysis. The three potential binding peptides of MgPa may provide some experimental evidence for further understanding the biological functions of MgPa and pathogenic mechanisms of M. genitalium.
摘要:
Exposure to Mycoplasma pneumoniae leads to lung inflammation through a host defense pathway. Increasing evidence has indicated that the mycoplasma-derived membrane lipoprotein, or its analogue macrophage-activating lipopeptide-2 (MALP-2), excretes LPS as an immune system-stimulating substance and plays a crucial role in pathological injury during M. pneumoniae infection. It has been established that Sulforaphane confers anti-inflammatory properties. However, the underlying mechanism responsible for the inhibitory actions of Sulforaphane in the context of mycoplasmal pneumoniae are poorly understood. Here, we report that Sulforaphane is an inducer of heme oxygenase (HO)-1, a cytoprotective enzyme that catalyzes the degradation of heme through signaling pathways in human monocytes. Sulforaphane stimulated NF-E2-related factor 2 (Nrf2) translocation from the cytosol to the nucleus, and small interfering RNA-mediated knock-down of Nrf2 significantly inhibited Sulforaphane-induced HO-1 expression. Additionally, PI3K/Akt and ROS were also involved in Sulforaphane-induced Nrf2 activation and HO-1 expression, as revealed by the pharmacological inhibitors LY294002 and NAC. Moreover, Sulforaphane treatment inhibited MALP-2-induced pro-inflammatory cytokine secretion and pulmonary inflammation in mice, as well as MALP-2-triggered NF-kappaB activation. Furthermore, SnPP, a selective inhibitor of HO-1, reversed the inhibitory actions of Sulforaphane, while a carbon monoxide-releasing molecule, CORM-2, caused a significant decrease in MALP-2-induced cytokine secretion. Collectively, these results suggest that Sulforaphane functions as a suppressor of the MALP-2-induced inflammatory response, not only by inhibiting the expression of cytokines and the induction of HO-1 but also by diminishing NF-kappaB activation in cultured monocytes and the lungs of mice.
摘要:
Although Chlamydia has been frequently detected in the gastrointestinal tracts of both humans and animals, it is not associated with any gastrointestinal pathology. We have recently shown that gastrointestinal Chlamydia muridarum is not only non-pathogenic but also induces protective immunity in the genital tract. We now report that the transmucosal immunity induced by a single oral immunization with C. muridarum protected the mouse airway from a subsequent challenge infection. The oral immunization significantly reduced chlamydial burden in the airway as early as day 3 after intranasal challenge. As a result, the airway chlamydial spreading to extra-airway tissues was completely prevented on day 3 and significantly reduced on day 9. The immunized mice were protected from any significant systemic toxicity caused by the intranasal challenge since there was no significant bodyweight drop in the immunized mice. This robust protection correlated well with Chlamydia-specific antibodies that recognize chlamydial organism surface antigens and T cell responses that are dominated with a Th1 phenotype. The immunized mice developed high ratios of IgG2b/c over IgG1 levels and IFN gamma-producing over IL-5 or IL-13-producing lymphocytes. Thus, we have demonstrated that oral vaccination with C muridarum can induce Th1-dominant transmucosal immunity in the airway. Together with previous studies, we propose that non-pathogenic colonization of Chlamydia in the gastrointestinal tract be explored as an oral delivery system for inducing protection against infections and pathologies in extra-gastrointestinal tissues. (C) 2018 Elsevier Ltd. All rights reserved.
摘要:
Mycoplasma genitalium adhesion protein (MgPa) is a major adhesin of M. genitalium, a human pathogen associated with a series of genitourinary tract diseases. MgPa plays a very important role in M. genitalium adhering to the host cells. However, the exact receptor peptides or proteins of MgPa are still poorly understood so far. Three polypeptides (V-H-W-D-F-R-Q-W-W-Q-P-S), (D-W-S-S-W-V -Y-R-D-P-Q-T) and (H-Y-I-D-F-R-W) were previously screened from a phage display random peptide library using recombinant MgPa (rMgPa) as a target molecule. In this study, three polypeptides were artificially synthesized and investigated as to whether they are potential receptors of MgPa. We found that rMgPa specifically bound to three synthesized polypeptides as determined via an indirect enzyme-linked immunosorbent assay (ELISA). Moreover, three polypeptides were further identified by indirect immunofluorescence microscopy (IFM). We confirmed that rMgPa and M. genitalium can adhere to SV-HUC-1 cells in vitro and that anti-rMgPa antibody and three synthesized polypeptides can partially inhibit the adherence of rMgPa and M. genitalium to SV-HUC-1 cells. In summary, these three polypeptides may be the essential receptor peptides of MgPa, and may aid in enhancing the understanding of biological function of MgPa and the possible pathogenic mechanism of M. genitalium.
通讯机构:
Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, China