Staphylococcin C55

Objectives: To evaluate the clinical efficacy of highly agglutinative staphylococcin combined with neoadjuvant chemotherapy on patients with intermediate or advanced oral cancer. Methods: A total of 80 patients with intermediate or advanced oral cancer treated in Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine from January 2020 to January 2022 were included. Patients were divided into two groups based on their treatment choice, with 40 cases in each group. Patients in the control group were given paclitaxel combined with cisplatin chemotherapy regimen: paclitaxel 150 mg/m2 and cisplatin 100 mg/m2 on Day-1, with 28 days as one cycle of chemotherapy for a total of three cycles. Patients in the experimental group received intramuscular injection of 500U highly agglutinative staphylococcin once a day for two weeks on the basis of chemotherapy, and continued the next course of treatment after 1 week of withdrawal, with a total of two courses. After treatment, the therapeutic effect, adverse drug reactions, changes in tumor markers such as CEA, NSE, CA19-9 and CA125 before and after treatment, as well as differences in levels of CD3+, CD4+, CD8+ and CD4+/CD8+ of T lymphocyte subsets between the two groups before and after treatment were compared and analyzed. Results: The total efficacy of the experimental group was 80%, which was significantly better than 57.5% of the control group (P=0.03). The incidence of adverse drug reactions in the experimental group was 17.5%, while that in the control group was 42.5%, showing a statistically significant difference (P=0.02), and the WBC count decreased more significantly in the control group (P=0.04). CEA, NSE, CA19-9 and CA125 decreased significantly in the experimental group after treatment compared with the control group, with a statistically significant difference (P=0.00). Moreover, the levels of CD3+, CD4+, CD4+/CD8+ in the experimental group after treatment were significantly higher than those in the control group, with statistically significant differences (CD3+, P=0.03; CD4+, P=0.00; CD4+/CD8+, P=0.00), while CD8+ did not change significantly (P=0.95). Conclusions: Highly agglutinative staphylococcin combined with chemotherapy is a safe and effective treatment regimen with definite curative effect for patients with intermediate or advanced oral cancer. With such a regimen, tumor markers are remarkably reduced, immune function can be significantly improved, and adverse reactions will be evidently reduced.

Background: Two component lantibiotics, such as the plasmid-encoded lacticin 3147 produced by Lactococcus lactis DPC3147 and staphylococcin C55 produced by Staphylococcus aureus C55, represent an emerging subgroup of bacteriocins. These two bacteriocins are particularly closely related, exhibiting 86% (LtnA1 and C55alpha) and 55% (LtnA2 and C55beta) identity in their component peptides. The aim of this study was to investigate, for the first time for any two component bacteriocins, the significance of the relatedness between these two systems. Results: So close is this relatedness that the hybrid peptide pairs LtnA1:C55beta and C55alpha:LtnA2 were found to have activities in the single nanomolar range, comparing well with the native pairings. To determine whether this flexibility extended to the associated post-translational modification/processing machinery, the staphylococcin C55 structural genes were directly substituted for their lacticin 3147 counterparts in the ltn operon on the large conjugative lactococcal plasmid pMRC01. It was established that the lacticin LtnA1 post-translational and processing machinery could produce functionally active C55alpha, but not C55beta. In order to investigate in closer detail the significance of the differences between LtnA1 and C55alpha, three residues in LtnA1 were replaced with the equivalent residues in C55alpha. Surprisingly, one such mutant LtnA1-Leu21Ala was not produced. This may be significant given the positioning of this residue in a putative lipid II binding loop. Conclusion: It is apparent, despite sharing striking similarities in terms of structure and activity, that these two complex bacteriocins display some highly dedicated features particular to either system.

This review article summarized 100 published research papers and reviewed the application status of highly agglutinative staphylococcin in the clinical treatment of cancer. Highly agglutinative staphylococcin (HAS) derives from the superantigen of Staphylococcus aureus metabolite. Studies have shown that HAS can inhibit and kill tumors, repair tissues and cells, increase white blood cell count and improve the immune function. Its immunological effect acts through the following mechanism: activating T-cells and natural killer cells, enhancing phagocytes' phagocytosis and killing ability of lymphocytes, increasing white blood cell count in peripheral blood, repairing impaired histocytes, and inhibit the growth of tumor cells. Highly agglutinative staphylococcin is used in clinical treatment of tumors: intracavitary hyperthermic perfusion with single HAS is effective for malignant ascites; perfusion with HAS plus chemotherapeutics can remarkably improve the elimination rate of ascites. Highly agglutinative staphylococcin can also enhance the effect of and improve the response rate of chemotherapy and radiotherapy, and improve patients' immune function and relieve gastrointestinal reactions caused by radiotherapy and chemotherapy. Therefore, HAS is used to treat a malignant tumor, leucocytopenia, and malignant ascites, and relieve side effects caused by radiotherapy and chemotherapy and improve patients' immune function.