A Drug Repositioning Approach Reveals that Streptococcus mutans Is Susceptible to a Diverse Range of Established Antimicrobials and Nonantibiotics.

Streptococcus mutans is the primary causative agent of dental caries and contributes to the multispecies biofilm known as dental plaque. An adenylate kinase-based assay was optimized for S. mutans to detect cell lysis when exposed to the Selleck library (Selleck Chemical, Houston, TX) of 853 FDA-approved drugs in, to our knowledge, the first high-throughput drug screen in S. mutans We found 126 drugs with activity against S. mutans planktonic cultures, and they were classified into six categories: antibacterials (61), antineoplastics (23), ion channel effectors (9), other antimicrobials (7), antifungals (6), and other (20). These drugs were also tested for activity against S. mutans biofilm cultures, and 24 compounds were found to inhibit biofilm formation, 6 killed preexisting biofilms, 84 exhibited biofilm inhibition and killing activity, and 12 had no activity against biofilms. The activities of 9 selected compounds that exhibited antimicrobial activity were further characterized for their activity against S. mutans planktonic and biofilm cultures. Together, our results suggest that S. mutans exhibits a susceptibility profile to a diverse array of established and novel antibacterials.

Vitamin D Compounds Are Bactericidal against Streptococcus mutans and Target the Bacitracin-Associated Efflux System.

Vitamin D analogs were identified as compounds that induced lysis of planktonic cultures of Streptococcus mutans in a high-throughput screen of FDA-approved drugs. Previous studies have demonstrated that certain derivatives of vitamin D possess lytic activity against other bacteria, though the mechanism has not yet been established. Through the use of a combinatorial approach, the vitamin D derivative doxercalciferol was shown to act synergistically with bacitracin, a polypeptide-type drug that is known to interfere with cell wall synthesis, suggesting that doxercalciferol may act in a bacitracin-related pathway. Innate resistance to bacitracin is attributed to efflux by a conserved ABC-type transporter, which in S. mutans is encoded by the mbrABCD operon. S. mutans possesses two characterized mechanisms of resistance to bacitracin, the ABC transporter, S. mutans bacitracin resistance (Mbr) cassette, consisting of MbrABCD, and the rhamnose-glucose polysaccharide (Rgp) system, RgpABCDEFGHI. Loss of function of the transporter in ΔmbrA and ΔmbrD mutants exacerbated the effect of the combination of doxercalciferol and bacitracin. Despite conservation of a transporter homologous to mbrABCD, the combination of doxercalciferol and bacitracin appeared to be synergistic only in streptococcal species. We conclude that vitamin D derivatives possess lytic activity against S. mutans and act through a mechanism dependent on the bacitracin resistance mechanism of MbrABCD.

Male breast cancer: 6-year experience.

AIM: Breast cancer in men is a very rare neoplasm accounting 1% of all breast cancer with an incidence ratio of 1:100 of men to women and about 1% of all malignancies in men. On the basis of the literature review the authors tried to determine the main characteristics of this rare neoplasm in terms of epidemiology, diagnosis, prognosis, treatment and survival. METHODS: The authors report the experience of the Breast Unit of the San Giovanni Addolorata Hospital in Rome, where 4 cases of male breast cancer were observed and treated over 784 breast cancers. RESULTS: All tumours were ductal carcinomas. The extent of disease was as follows: 3 cases with stage I and 1 case with Stage IIIB; in two cases estrogen and progesterone receptors expression was 100% and in the other two cases it was 20-80%. Median follow up was 57.5 months. At present, after 6-year follow up the three patients with stage I are in good conditions; the patient with stage III died after 27 months with metastatic disease. CONCLUSIONS: Surgical treatment remains the gold standard in male breast cancer. The prognosis for males with breast cancer is similar to female patients on equal terms of stage of disease. Adjuvant therapy is based on retrospective studies of male breast cancer conducted over the past 20 years using the guidelines for breast cancer in women.

Locoregional IL-2 therapy in the treatment of colon cancer. Cell-induced lesions of a murine model.

BACKGROUND: Local therapy with IL-2 may be very effective in the treatment of different forms of cancer. The aim of this study was to determine the effectiveness of IL-2 locoregional application in the treatment of colon cancer. MATERIALS AND METHODS: Twenty eight syngenic BDIX rats were utilized in this study. The rats were divided into two groups of fourteen animals: group T (treatment) and group C (control). All rats of both groups were injected, under the splenic capsule, with T 10(7) DHD/K2/ TRb neoplastic cells. Then, within and around the site of the previous inoculation, the T group was injected with 1 ml of glucosate solutions + 0.1% albumin (BSA) containing 2.5 x 10(6) IU of IL-2 ( Proleukin-Chiron), whereas the C group was injected with 1 ml of BSA alone. After three weeks, rats were sacrificed and the liver and spleen were removed. The following parameters were considered: volume and weight, neoplastic-non neoplastic tissue index of the spleen, mitotic index and vascular density of splenic and hepatic lesions. RESULTS: All the studied parameters showed statistically significant differences in treated and untreated animals. CONCLUSION: This study of a murine model demonstrated that IL-2 locoregional therapy may be effective in the treatment of colon cancer.