HOXB13 is co-localized with androgen receptor to suppress androgen-stimulated prostate-specific antigen expression / 대한해부학회지

During the prostate cancer (PCa) development and its progression into hormone independency, androgen receptor (AR) signals play a central role by triggering the regulation of target genes, including prostate-specific antigen. However, the regulation of these AR-mediated target genes is not fully understood. We have previously demonstrated a unique role of HOXB13 homeodomain protein as an AR repressor. Expression of HOXB13 was highly restricted to the prostate and its suppression dramatically increased hormone-activated AR transactivation, suggesting that prostate-specific HOXB13 was a highly potent transcriptional regulator. In this report, we demonstrated the action mechanism of HOXB13 as an AR repressor. HOXB13 suppressed androgen-stimulated AR activity by interacting with AR. HOXB13 did neither bind to AR responsive elements nor disturb nuclear translocation of AR in response to androgen. In PCa specimen, we also observed mutual expression pattern of HOXB13 and AR. These results suggest that HOXB13 not only serve as a DNA-bound transcription factor but play an important role as an AR-interacting repressor to modulate hormone-activated androgen receptor signals. Further extensive studies will uncover a novel mechanism for regulating AR-signaling pathway to lead to expose new role of HOXB13 as a non-DNA-binding transcriptional repressor.

Growth of Streptonigrin-Resistant Staphylococcus epidermidis with Defective Siderophore-Mediated Iron-Uptake System in Human Peritoneal Dialysate Solution / 감염과화학요법

BACKGROUND: Staphylococcus epidermidis is the most common pathogen of chronic ambulatory peritoneal dialysis peritonitis. It has been believed that the activity of iron-uptake system (IUS) may play an important role in the growth of S. epidermidis in human peritoneal dialysate (HPD) solution, but there is no report using mutants with defective IUS. A streptonigrin-resistant S. epidermidis (SRSE) strain was isolated from S. epidermidis KCTC 1917 and functionally characterized. MATERIALS AND METHODS: Bacterial growth was monitored by measuring the optical densities of culture fluids obtained at appropriate intervals at a wavelength of 600 nm. CAS agar diffusion assay was used for the comparison of siderophore production, 6 M urea-gel electrophoresis for the comparison of the ability to capture iron from transferrin, and bioassay for the observation of the ability to utilize iron-siderophore complexes. RESULTS: The SRSE strain ineffectively utilized transferrin-bound iron for growth despite its ability to produce considerably larger amount of siderophores than its parental strain. The growth of the parental strain, but not the SRSE strain, was stimulated on transferrin-bound iron by its own siderophores each. The growth of the SRSE strain in the HPD solution was retarded compared to that of the parental strain. CONCLUSION: These results indicate that the SRSE strain is defective in its ability to utilize the iron-siderophore complexes, rather than its ability to produce siderophores, and that the siderophore-mediated IUS plays an important role in the growth of S. epidermidis in HPD solution.

Growth of Streptonigrin-Resistant Staphylococcus epidermidis with Defective Siderophore-Mediated Iron-Uptake System in Human Peritoneal Dialysate Solution / 감염과화학요법

BACKGROUND: Staphylococcus epidermidis is the most common pathogen of chronic ambulatory peritoneal dialysis peritonitis. It has been believed that the activity of iron-uptake system (IUS) may play an important role in the growth of S. epidermidis in human peritoneal dialysate (HPD) solution, but there is no report using mutants with defective IUS. A streptonigrin-resistant S. epidermidis (SRSE) strain was isolated from S. epidermidis KCTC 1917 and functionally characterized. MATERIALS AND METHODS: Bacterial growth was monitored by measuring the optical densities of culture fluids obtained at appropriate intervals at a wavelength of 600 nm. CAS agar diffusion assay was used for the comparison of siderophore production, 6 M urea-gel electrophoresis for the comparison of the ability to capture iron from transferrin, and bioassay for the observation of the ability to utilize iron-siderophore complexes. RESULTS: The SRSE strain ineffectively utilized transferrin-bound iron for growth despite its ability to produce considerably larger amount of siderophores than its parental strain. The growth of the parental strain, but not the SRSE strain, was stimulated on transferrin-bound iron by its own siderophores each. The growth of the SRSE strain in the HPD solution was retarded compared to that of the parental strain. CONCLUSION: These results indicate that the SRSE strain is defective in its ability to utilize the iron-siderophore complexes, rather than its ability to produce siderophores, and that the siderophore-mediated IUS plays an important role in the growth of S. epidermidis in HPD solution.

Utilization of Transferrin-Bound Iron by Medically Important Staphylococcal Species

Staphylococcus aureus is able to utilize efficiently transferrin-bound iron as an iron source, whereas other staphylococci are not. The reason for this difference remains unclear. We compared the activity of siderophore-mediated iron-uptake systems among S. aureus, S. epidermidis, and S. saprophyticus. S. aureus was more susceptible to streptonigrin than the other two staphylococci. S. aureus was able to utilize efficiently transferrin-bound iron in proportion to the level of iron-saturation and produced siderophores in an inverse relation to iron-saturation. In contrast to S. aureus, S. epidermidis and S. saprophyticus were able to utilize only holotransferrin (HT; about 80% iron- saturated) and produced siderophores only in media containing HT. Moreover, they utilized HT less efficiently than S. aureus, though they produced greater amount of siderophores than S. aureus in media containing HT. The ability of the equivalent siderophores per se to capture iron from HT was not significantly different among the three species. Nevertheless, the siderophores from S. aureus stimulated the growth of the staphylococci to a greater degree than did the siderophores from S. epidermidis and S. saprophyticus. The siderophores from S. epidermidis and S. saprophyticus also stimulated the growth of S. aureus to a greater degree than those of the original bacteria which produced them. This indicates that S. aureus possesses a greater ability to produce more-efficient siderophores responding to very low iron-availability, as well as a greater ability to utilize iron-siderophore complexes, than the other two staphylococci. This explains in part the higher virulence of S. aureus compared to other staphylococci.