Faecal carriage of CTX-M-type ESBL-producing Enterobacteriaceae among asymptomatic individuals in rural Thailand remains alarmingly high, and previous antibiotic use and a history of hospitalization may contribute to its dissemination.
Although many antibiotics are available for the treatment of bacterial infections, the emergence and global spread of antibiotic-resistant bacteria is a community-wide problem. To overcome this problem, we must explore alternative antimicrobials. This study investigated the antibacterial properties of quercetin, a flavonoid present in vegetables and fruits. Quercetin was tested against gram-positive and gram-negative bacteria and was found to exert selective antibacterial activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), and Staphylococcus epidermidis. Some clinical MRSA strains showed remarkable susceptibility to quercetin. In combination with antibiotics, such as oxacillin, ampicillin, vancomycin, gentamicin, and erythromycin, quercetin showed markedly enhanced antibacterial activity against MRSA. We also report quercetin-induced aggregation of S. aureus cells; the morphological changes in these cells, as assessed by electron microscopy; and the colony-spreading ability of quercetin-sensitive MRSA, all of which revealed the unique antibacterial properties of quercetin against S. aureus.
Rad9, Rad1, and Hus1 are members of the Rad family of checkpoint proteins that are required for both DNA replication and DNA damage checkpoints and are thought to function as sensors in the DNA integrity checkpoint control. These proteins can interact with each other and form a stable proliferating cell nuclear antigen-related Rad9⅐Rad1⅐Hus1 heterotrimeric complex that might encircle DNA at or near the damaged sites. In this study, we demonstrate that the human Rad9 (hRad9) protein contains a predicted nuclear localization sequence (NLS) near its C terminus, which plays an essential role in the hRad9-mediated G 2 checkpoint. Deletion experiments indicate that the NLS-containing region of hRad9 is critical for the nuclear transport of not only hRad9 but also human Rad1 (hRad1) and human Hus1 (hHus1), although this region is not required for hRad9⅐hRad1⅐hHus1 complex formation. In support of the role that hRad9 NLS plays in the nuclear targeting of the hRad9⅐hRad1⅐hHus1 complex, overexpression of a deletion mutant of hRad9 lacking the NLS-containing C-terminal region can bypass the G 2 checkpoint and result in cell death after ionizing radiation or hydroxyurea treatment. Moreover, knockdown of hRad9 expression by small interfering RNA (siRNA) results in hRad1 accumulation in the cytoplasm and significantly abrogates the G 2 checkpoint in the presence of damaged DNA or incomplete DNA replication. Thus, the C-terminal region of human Rad9 protein is important for G 2 checkpoint control by operating the transport of the hRad9⅐hRad1⅐hHus1 checkpoint complex into the nucleus.
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