Staphylococci are frequent human commensals and some species can cause disease. Staphylococcus aureus in particular is a dangerous human pathogen. In staphylococci, the ability to sense the bacterial cell density, or quorum, and to respond with genetic adaptations is due to one main system, which is called accessory gene regulator (Agr). The extracellular signal of Agr is a post-translationally modified peptide containing a thiolactone structure. Under conditions of high cell density, Agr is responsible for the increased expression of many toxins and degradative exoenzymes, and decreased expression of several colonization factors. This regulation is important for the timing of virulence factor expression during infection and the development of acute disease, while low activity of Agr is associated with chronic staphylococcal infections, such as those involving biofilm formation. Accordingly, drugs inhibiting Agr are being evaluated for their capacity to control acute forms of S. aureus infection.
Objective To evaluate a 12-session home and community-based health promotion/obesity prevention program (Challenge!) on changes in BMI, body composition, physical activity (PA), and diet. Methods 235 African-American adolescents (11–16 yrs, 38% overweight/obese) were recruited from low-income urban communities. Baseline measures included weight, height, body composition (dual-energy x-ray absorptiometry (DEXA) and bioelectrical impedance), physical activity (PA) (accelerometry), and diet (food frequency). PA was measured by time in play-equivalent physical activity (PEPA≥1800 activity counts/min). Participants were randomized into a home- and community-based health promotion/obesity prevention controlled trial, anchored in social cognitive theory and involving motivational interviewing techniques, and delivered by college-enrolled, African-American mentors. Control adolescents did not receive the intervention or a mentor. Post-intervention (10 mos) and delayed follow-up (24 mos) evaluations were conducted. Longitudinal analyses using random mixed effects models and generalized estimating equations (GEE) examined direct and moderated effects of time, gender, and baseline BMI category on changes at both follow-ups. Results Retention was 76% (178/235) over 2 years; overweight/obese status declined 5.3% among intervention adolescents and increased 11.3% among control adolescents (χ2=5.8, p=0.02, GEE). Among males, but not females, fat free mass was significantly higher among intervention members at both follow-up evaluations. PA effects were moderated by baseline BMI category; among adolescents ≥ 85th percentile, control adolescents averaged 25.5 min less daily activity than intervention adolescents (p=0.018) at the 10-mo, but not the 24-mo follow-up. Intervention adolescents declined significantly more in snack and dessert consumption than control adolescents (p=0.045). Conclusion A 12-session, home-and community-based intervention, based on social cognitive theory and delivered by college-enrolled mentors, had sustained effects over 24 months in preventing an increase in BMI category, in enhancing fat free mass among males, and in reducing snack and dessert intake. The intervention prevented PA declines among the heaviest adolescents, but effects were not sustained.
Prior reports regarding the association between physical activity and subclinical cardiovascular disease have not been consistent. The authors assessed physical activity and walking pace via questionnaire among 6,482 US adults aged 45-84 years without prior clinical cardiovascular disease participating in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2002. Ankle-brachial index (ABI), coronary artery calcification, and internal and common carotid intima-media thickness (IMT) were measured. Metabolic equivalent-hours/week of physical activity were calculated. These data were analyzed by using multivariable linear or relative prevalence regression in gender-specific strata. After adjustment for age, race/ethnicity, clinic site, education, income, and smoking (model 1), increasing total, moderate + vigorous, and intentional-exercise physical activity were not associated with IMT or coronary artery calcification in either gender. These factors were associated with increased ABI (P<0.05) in women only. Walking pace was associated favorably with common carotid IMT, ABI, and coronary artery calcification in men and with common carotid IMT and ABI in women (all P<0.05) after adjustment for model 1 variables. These associations were attenuated and, for common carotid IMT, no longer significant when lipids, hypertension, diabetes, and body mass index were added to the model. These data suggest that walking pace is associated with less subclinical atherosclerosis; these associations may be mediated by cardiovascular disease risk factors.
A home-based intervention founded on a mentorship model and targeted toward adolescent development, including negotiation skills, was effective in preventing rapid repeat births among low-income, black adolescent mothers. The effectiveness of the intervention could be seen after only 2 visits and increased over time. There were no second births among mothers who attended > or = 8 sessions. There was no evidence that risk behavior or contraceptive use was related to rapid second births. There was some evidence that rapid second births among adolescent mothers were regarded as desirable and as part of a move toward increasing autonomy and family formation, thereby undermining intervention programs that focus on risk avoidance. Findings suggest the merits of a mentoring program for low-income, black adolescent mothers, based on a relatively brief (6-8 sessions) curriculum targeted toward adolescent development and interpersonal negotiation skills.
The primary virulence factor of the skin commensal and opportunistic pathogen, Staphylococcus epidermidis, is the ability to form biofilms on surfaces of implanted materials. Much of this microorganism’s pathogenic success has been attributed to its ability to evade the innate immune system. The primary defense against S. epidermidis biofilm infection consists of complement activation, recruitment and subsequent killing of the pathogen by effector cells. Among pathogen-derived factors, the biofilm exopolysaccharide polysaccharide intercellular adhesion (PIA), as well as the accumulation-associated protein (Aap), and the extracellular matrix binding protein (Embp) have been shown to modulate effector cell-mediated killing of S. epidermidis. Phenol-soluble modulins (PSMs) constitute the only class of secreted toxins by S. epidermidis, at least one type of which (PSMδ) possesses strong cytolytic properties toward leukocytes. However, through selective production of non-cytolytic subtypes of PSMs, S. epidermidis is able to maintain a low inflammatory infection profile and avoid eradication by the host immune system. Taken together, our emerging understanding of the mechanisms behind immune modulation by S. epidermidis elucidates the microorganism’s success in the initial colonization of device surfaces as well as the maintenance of a chronic and indolent course of biofilm infection.
Staphylococcus aureus is a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specific S. aureus surface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such as the polysaccharide intercellular adhesin (PIA), with the bacterial cell surface. Together, our findings support a two-step model of staphylococcal prosthetic joint infection: As we previously reported, interaction of S. aureus surface proteins with host matrix proteins such as fibrin initiates agglomeration; our present results show that, thereafter, the bacterial agglomerates grow to extremely large sizes owing to the lack of PSM expression under the specific conditions present in joints. Our findings provide a mechanistic explanation for the reported extreme resistance of joint infection to antibiotic treatment, lend support to the notions that Agr functionality and PSM production play a major role in defining different forms of S. aureus infection, and have important implications for antistaphylococcal therapeutic strategies.
Staphylococci are frequently implicated in human infections, and continue to pose a therapeutic dilemma due to their ability to form deeply seated microbial communities, known as biofilms, on the surfaces of implanted medical devices and host tissues. Biofilm development has been proposed to occur in three stages: (1) attachment, (2) proliferation/structuring, and (3) detachment/dispersal. Although research within the last several decades has implicated multiple molecules in the roles as effectors of staphylococcal biofilm proliferation/structuring and detachment/dispersal, to date, only phenol soluble modulins (PSMs) have been consistently demonstrated to serve in this role under both in vitro and in vivo settings. PSMs are regulated directly through a density-dependent manner by the accessory gene regulator (Agr) system. They disrupt the non-covalent forces holding the biofilm extracellular matrix together, which is necessary for the formation of channels, a process essential for the delivery of nutrients to deeper biofilm layers, and for dispersal/dissemination of clusters of biofilm to distal organs in acute infection. Given their relevance in both acute and chronic biofilm-associated infections, the Agr system and the psm genes hold promise as potential therapeutic targets.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.