Characterization of transcription within sdr region of Staphylococcus aureus

Staphylococcus aureus is an opportunistic pathogen responsible for various infections in humans and animals. It causes localized and systemic infections, such as abscesses, impetigo, cellulitis, sepsis, endocarditis, bone infections, and meningitis. S. aureus virulence factors responsible for the initial contact with host cells (MSCRAMMs—microbial surface components recognizing adhesive matrix molecules) include three Sdr proteins. The presence of particular sdr genes is correlated with putative tissue specificity. The transcriptional organization of the sdr region remains unclear. We tested expression of the sdrC, sdrD, or sdrE genes in various in vitro conditions, as well as after contact with human blood. In this work, we present data suggesting a separation of the sdr region into three transcriptional units, based on their differential reactions to the environment. Differential reaction of the sdrD transcript to environmental conditions and blood suggests dissimilar functions of the sdr genes. SdrE has been previously proposed to play role in bone infections, whilst our results can indicate that sdrD plays a role in the interactions between the pathogen and human immune system, serum or specifically reacts to nutrients/other factors present in human blood

Staphylococcus aureus Manganese Transport Protein C Is a Highly Conserved Cell Surface Protein That Elicits Protective Immunity Against S. aureus and Staphylococcus epidermidis

Staphylococcus aureus and other staphylococci cause severe human disease, and there are currently no vaccines available. We evaluated whether manganese transport protein C (MntC), which is conserved across the staphylococcal species group, could confer protection against S. aureus and Staphylococcus epidermidis. In vivo analysis of S. aureus MntC expression revealed that expression occurs very early during the infectious cycle. Active immunization with MntC was effective at reducing the bacterial load associated with S. aureus and S. epidermidis infection in an acute murine bacteremia model. Anti-MntC monoclonal antibodies have been identified that can bind S. aureus and S. epidermidis cells and are protective in an infant rat passive protection model and induce neutrophil respiratory burst activity. This is the first description of a protein that has the potential to provide protection across the staphylococcal species group

Staphylococcus aureus Host Cell Invasion and Virulence in Sepsis Is Facilitated by the Multiple Repeats within FnBPA

Entry of Staphylococcus aureus into the bloodstream can lead to metastatic abscess formation and infective endocarditis. Crucial to the development of both these conditions is the interaction of S. aureus with endothelial cells. In vivo and in vitro studies have shown that the staphylococcal invasin FnBPA triggers bacterial invasion of endothelial cells via a process that involves fibronectin (Fn) bridging to α5β1 integrins. The Fn-binding region of FnBPA usually contains 11 non-identical repeats (FnBRs) with differing affinities for Fn, which facilitate the binding of multiple Fn molecules and may promote integrin clustering. We thus hypothesized that multiple repeats are necessary to trigger the invasion of endothelial cells by S. aureus. To test this we constructed variants of fnbA containing various combinations of FnBRs. In vitro assays revealed that endothelial cell invasion can be facilitated by a single high-affinity, but not low-affinity FnBR. Studies using a nisin-inducible system that controlled surface expression of FnBPA revealed that variants encoding fewer FnBRs required higher levels of surface expression to mediate invasion. High expression levels of FnBPA bearing a single low affinity FnBR bound Fn but did not invade, suggesting that FnBPA affinity for Fn is crucial for triggering internalization. In addition, multiple FnBRs increased the speed of internalization, as did higher expression levels of FnBPA, without altering the uptake mechanism. The relevance of these findings to pathogenesis was demonstrated using a murine sepsis model, which showed that multiple FnBRs were required for virulence. In conclusion, multiple FnBRs within FnBPA facilitate efficient Fn adhesion, trigger rapid bacterial uptake and are required for pathogenesis

Postpartum depression in the Occupied Palestinian Territory:a longitudinal study in Bethlehem

BACKGROUND: Postpartum depression (PPD) affects women from different cultures around the world. No previous studies have investigated PPD among women in Palestine. Fertility rates in Palestine are among the highest in the world, hence even low rates of PPD could have considerable national impact. The aim of this study was to determine the prevalence of, and risk factors for, PPD among Palestinian mothers. METHODS: 101 mothers were recruited during the registration of their child’s birth (within 1 week) at the Bethlehem branch of the Ministry of Interior. Participants were assessed via a face to face interview, and were followed up 1 week, 2 weeks, 6 weeks, 3 months, and 6 months later by telephone interview. Interviews included the Arabic Edinburgh Postnatal Depression Scale (EPDS), with PPD indicated by depressive symptoms (EPDS score ≥11) at ≥2 follow-up time points. Pearson’s correlation was calculated between repeated EPDS scores, and multivariable logistic regression was used to investigate risk factors for PPD. RESULTS: The prevalence of depressive symptoms was fairly constant (14–19%) over the follow-up period. Most depressive symptoms developed within 1 month of delivery; mothers with depressive symptoms at 3 months postpartum were highly likely to still have symptoms at 6 months. 27.7% (28/101) of women met our criteria for PPD. High parity (odds ratio (OR) 4.52 (95% CI 0.90, 22.8) parity 3+ versus primiparous), unplanned pregnancy (OR 2.44 (0.99, 6.01)) and sex of child not being the one desired (OR 5.07 (1.12, 22.9)) were associated with PPD, but these associations were attenuated in multivariable analysis. CONCLUSIONS: The prevalence of PPD in Palestine appears to be higher than in high income countries, but similar to the prevalence in other Middle Eastern countries. High parity and unplanned pregnancy were identified as risk factors for PPD, suggesting that fully meeting the need for family planning could reduce the incidence of PPD in the Palestinian population

Hemocompatibility of Silicon-Based Substrates for Biomedical Implant Applications

Silicon membranes with highly uniform nanopore sizes fabricated using microelectromechanical systems (MEMS) technology allow for the development of miniaturized implants such as those needed for renal replacement therapies. However, the blood compatibility of silicon has thus far been an unresolved issue in the use of these substrates in implantable biomedical devices. We report the results of hemocompatibility studies using bare silicon, polysilicon, and modified silicon substrates. The surface modifications tested have been shown to reduce protein and/or platelet adhesion, thus potentially improving biocompatibility of silicon. Hemocompatibility was evaluated under four categories—coagulation (thrombin–antithrombin complex, TAT generation), complement activation (complement protein, C3a production), platelet activation (P-selectin, CD62P expression), and platelet adhesion. Our tests revealed that all silicon substrates display low coagulation and complement activation, comparable to that of Teflon and stainless steel, two materials commonly used in medical implants, and significantly lower than that of diethylaminoethyl (DEAE) cellulose, a polymer used in dialysis membranes. Unmodified silicon and polysilicon showed significant platelet attachment; however, the surface modifications on silicon reduced platelet adhesion and activation to levels comparable to that on Teflon. These results suggest that surface-modified silicon substrates are viable for the development of miniaturized renal replacement systems

Sequence Diversities of Serine-Aspartate Repeat Genes among Staphylococcus aureus Isolates from Different Hosts Presumably by Horizontal Gene Transfer

BACKGROUND: Horizontal gene transfer (HGT) is recognized as one of the major forces for bacterial genome evolution. Many clinically important bacteria may acquire virulence factors and antibiotic resistance through HGT. The comparative genomic analysis has become an important tool for identifying HGT in emerging pathogens. In this study, the Serine-Aspartate Repeat (Sdr) family has been compared among different sources of Staphylococcus aureus (S. aureus) to discover sequence diversities within their genomes. METHODOLOGY/PRINCIPAL FINDINGS: Four sdr genes were analyzed for 21 different S. aureus strains and 218 mastitis-associated S. aureus isolates from Canada. Comparative genomic analyses revealed that S. aureus strains from bovine mastitis (RF122 and mastitis isolates in this study), ovine mastitis (ED133), pig (ST398), chicken (ED98), and human methicillin-resistant S. aureus (MRSA) (TCH130, MRSA252, Mu3, Mu50, N315, 04-02981, JH1 and JH9) were highly associated with one another, presumably due to HGT. In addition, several types of insertion and deletion were found in sdr genes of many isolates. A new insertion sequence was found in mastitis isolates, which was presumably responsible for the HGT of sdrC gene among different strains. Moreover, the sdr genes could be used to type S. aureus. Regional difference of sdr genes distribution was also indicated among the tested S. aureus isolates. Finally, certain associations were found between sdr genes and subclinical or clinical mastitis isolates. CONCLUSIONS: Certain sdr gene sequences were shared in S. aureus strains and isolates from different species presumably due to HGT. Our results also suggest that the distributional assay of virulence factors should detect the full sequences or full functional regions of these factors. The traditional assay using short conserved regions may not be accurate or credible. These findings have important implications with regard to animal husbandry practices that may inadvertently enhance the contact of human and animal bacterial pathogens

Type distribution, viral load and integration status of high-risk human papillomaviruses in pre-stages of cervical cancer (CIN)

A series of 176 archival cervical intraepithelial neoplasia (CIN) was analysed for the presence, viral load and integration status of ‘high-risk' types of human papillomavirus (HR-HPV). The samples were assayed using newly developed methods based on real-time PCR. Two methods for the extraction of DNA from the paraffin-embedded biopsies were compared: a protocol based on the MagNA pure system (Roche) and a Qiagen spin column kit (Qiagen). It was possible to amplify 94% (166) of the samples. Of these, 36, 63 and 80% of the CIN I, II and III cases contained HR-HPV. HPV 16 was the most prevalent, and was found in 20, 28 and 46% of the CIN I, II and III cases, respectively. The second most frequent HR-HPV was type 33 group, and in CIN II it was as prevalent as HPV 16. The median number of copies of HR-HPV per cell was not significantly different in the CIN I, II and III cases, but there was a wide range of viral load values over several magnitudes, regardless of the grade of CIN. All samples were found to contain integrated forms of HPV 16, frequently mixed with an episomal form

What is the value of orthodontic treatment?

Orthodontic treatment is as popular as ever. Orthodontists frequently have long lists of people wanting treatment and the cost to the NHS in England was £258m in 2010-2011 (approximately 10% of the NHS annual spend on dentistry). It is important that clinicians and healthcare commissioners constantly question the contribution of interventions towards improving the health of the population. In this article, the authors outline some of the evidence for and against the claims that people with a malocclusion are at a disadvantage compared with those without a malocclusion and that orthodontic treatment has significant health benefits. The authors would like to point out that this is not a comprehensive and systematic review of the entire scientific literature. Rather the evidence is presented in order to stimulate discussion and debate