Project description:Unlike USA300, a strain of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), commensal Staphylococcus aureus (S. aureus) bacteria isolated from human skin demonstrated the ability to mediate the glycerol fermentation to produce short-chain fatty acids (SCFAs). Quantitative proteomic analysis of enzymes involved in glycerol fermentation demonstrated that the expression levels of six enzymes, including glycerol-3-phosphate dehydrogenase (GPDH) and phosphoglycerate mutase (PGM), in commensal S. aureus are more than three-fold higher than those in USA300. Western blotting validated the low expression levels of GPDH in USA300, MRSA252 (a strain of hospital-acquired MRSA), and invasive methicillin-susceptible S. aureus (MSSA). In the presence of glycerol, commensal S. aureus effectively suppressed the growth of USA300 in vitro and in vivo. Active immunization of mice with lysates or recombinant α-hemolysin of commensal S. aureus or passive immunization with neutralizing sera provided immune protection against the skin infection of USA300. Our data illustrate for the first time that commensal S. aureus elicits both innate and adaptive immunity via glycerol fermentation and systemic antibody production, respectively, to fight off the skin infection of pathogenic MRSA.
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) colonization is a predictor of subsequent infection in hospitalized adults. The risk of subsequent MRSA infections in hospitalized children colonized with MRSA is unknown.Children admitted to an academic medical center's pediatric intensive care unit between March 2007 and March 2010 were included in the study. Anterior naris swabs were cultured to identify children with MRSA colonization at admission. Laboratory databases were queried and National Healthcare Safety Network definitions applied to identify patients with MRSA infections during their hospitalization or after discharge.The MRSA admission prevalence among 3140 children was 4.9%. Overall, 56 children (1.8%) developed an MRSA infection, including 13 (8.5%) colonized on admission and 43 (1.4%) not colonized on admission (relative risk [RR], 5.9; 95% confidence interval [CI], 3.4-10.1). Of those, 10 children (0.3%) developed an MRSA infection during their hospitalization, including 3 of 153 children (1.9%) colonized on admission and 7 of 2987 children (0.2%) not colonized on admission (RR, 8.4; 95% CI, 2.7-25.8). African-Americans and those with public health insurance were more likely to get a subsequent infection (P < .01 and P = .03, respectively). We found that 15 children acquired MRSA colonization in the pediatric intensive care unit, and 7 (47%) developed a subsequent MRSA infection.MRSA colonization is a risk factor for subsequent MRSA infection in children. Although MRSA colonized children may have lower risks of subsequent infection than adults, children who acquire MRSA in the hospital have similarly high rates of infection. Preventing transmission of MRSA in hospitalized children should remain a priority.
Project description:Countries such as Sweden that have a low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) offer the opportunity to discern and study transmission of imported cases of MRSA. We analyzed 444 imported cases of MRSA acquisition reported in Sweden during 2000-2003. Risk for MRSA in returning travelers ranged from 0.1 (95% confidence interval [CI] 0.01-0.4) per 1 million travelers to Nordic countries to 59.4 (95% CI 44.5-79.3) per 1 million travelers to North Africa and the Middle East. Most imported cases (246, 55%) were healthcare acquired, but regions with the highest risk for MRSA in travelers showed a correlation with community acquisition (r = 0.81, p = 0.001). Characteristic differences in MRSA strains acquired were dependent on the region from which they originated and whether they were community or healthcare acquired. Knowledge of differences in transmission of MRSA may improve control measures against imported cases.
Project description:Community-acquired infections caused by methicillin-resistant Staphylococcus aureus (MRSA) expressing the Panton-Valentine leukocidin (PVL) are rampant, but the contribution of PVL to bacterial virulence remains controversial. While PVL is usually viewed as a cytotoxin, at sublytic amounts it activates protective innate immune responses. A leukotoxic effect might predominate in high inoculum studies, whereas protective proinflammatory properties might predominate in settings with lower bacterial inocula that more closely mimic what initially occurs in humans. However, these protective effects might possibly be neutralized by antibodies to PVL, which are found in normal human sera and at increased levels following PVL(+) S. aureus infections. In a low-inoculum murine skin abscess model including a foreign body at the infection site, strains deleted for the pvl genes replicated more efficiently within abscesses than isogenic PVL(+) strains. Coinfection of mice at separate sites with isogenic PVL(+) and PVL(-) MRSA abrogated the differences in bacterial burdens, indicating a systemic effect on host innate immunity from production of PVL. Mice given antibody to PVL and then infected with seven different PVL(+) strains also had significantly higher bacterial counts in abscesses compared with mice given nonimmune serum. Antibody to PVL had no effect on MRSA strains that did not produce PVL. In vitro, antibody to PVL incapacitated PVL-mediated activation of PMNs, indicating that virulence of PVL(+) MRSA is enhanced by the interference of PVL-activated innate immune responses. Given the high rates of primary and recurring MRSA infections in humans, it appears that antibodies to PVL might contribute to host susceptibility to infection.
Project description:Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus endovascular infections. In this study, we investigated potential genetic mechanisms underlying the persistent outcomes. Compared with resolving bacteremia (RB) isolates (defined as isolates associated with negative results of blood cultures 2-4 days after initiation of therapy), PB strains (defined as isolates associated with positive results of blood cultures ≥7 days after initiation of therapy) had significantly earlier onset activation of key virulence regulons and structural genes (eg, sigB, sarA, sae, and cap5), higher expression of purine biosynthesis genes (eg, purF), and faster growth rates, with earlier entrance into stationary phase. Importantly, an isogenic strain set featuring a wild-type MRSA isolate, a purF mutant strain, and a purF-complemented strain and use of strategic purine biosynthesis inhibitors implicated a causal relationship between purine biosynthesis and the in vivo persistent outcomes. These observations suggest that purine biosynthesis plays a key role in the outcome of PB and may represent a new target for enhanced efficacy in treating life-threatening MRSA infections.
Project description:Next-generation sequencing (NGS) is a powerful tool for understanding both patterns of descent over time and space (phylogeography) and the molecular processes underpinning genome divergence in pathogenic bacteria. Here, we describe a synthesis between these perspectives by employing a recently developed Bayesian approach, BRATNextGen, for detecting recombination on an expanded NGS dataset of the globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clone ST239.The data confirm strong geographical clustering at continental, national and city scales and demonstrate that the rate of recombination varies significantly between phylogeographic sub-groups representing independent introductions from Europe. These differences are most striking when mobile non-core genes are included, but remain apparent even when only considering the stable core genome. The monophyletic ST239 sub-group corresponding to isolates from South America shows heightened recombination, the sub-group predominantly from Asia shows an intermediate level, and a very low level of recombination is noted in a third sub-group representing a large collection from Turkey.We show that the rapid global dissemination of a single pathogenic bacterial clone results in local variation in measured recombination rates. Possible explanatory variables include the size and time since emergence of each defined sub-population (as determined by the sampling frame), variation in transmission dynamics due to host movement, and changes in the bacterial genome affecting the propensity for recombination.
Project description:BackgroundNursing home residents experience a large burden of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Data are limited regarding nursing home characteristics associated with differences in facility-level invasive MRSA rates.MethodsWe analyzed 2011-2015 data from CDC's Emerging Infections Program (EIP) active population- and laboratory-based surveillance for invasive MRSA cases within seven states. A nursing home-onset case was defined as MRSA cultured from a normally sterile site in a person living in a nursing home 3 days before culture collection. Facility rates were calculated as nursing home-onset cases per 100,000 resident-days. Nursing home resident-day denominators and facility characteristics were obtained from four Centers for Medicare & Medicaid Services (CMS) datasets. A general estimating equations model with a logit link assessed characteristics of the facilities with highest rates comprising 50% of nursing home MRSA cases ("high rates").ResultsThe 626 nursing homes in the surveillance area had 2824 invasive MRSA cases; 82% of facilities had at ≥1 case. The 20% of facilities with highest rates (≥3.84 cases/100,000 resident-days) had 50% of nursing home-onset cases. In multivariable regression, facilities with high rates were more likely to have CMS-derived characteristics of presence of a resident with a multidrug-resistant organism; or greater proportions of residents who were male, were short stay (in the facility <100 days), had a nasogastric or percutaneous gastrostomy tube, or require extensive assistance with bed repositioning; and more likely to be in an EIP area with higher hospital-onset MRSA rates. Higher registered nurses staffing levels (hours/resident/day) and higher proportions of White residents were associated with lower rates.ConclusionsFacilities with higher invasive MRSA rates served residents with more clinical and functional care needs. Increasing registered nurse staffing in high-risk facilities might assist with reduction of invasive MRSA rates. These findings could help prioritize nursing homes for future MRSA prevention work.
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of health care-associated infections. Vancomycin remains an acceptable treatment option. There has been a welcome increase in the number of agents available for the treatment of MRSA infection. These drugs have certain differentiating attributes and may offer some advantages over vancomycin, but they also have significant limitations. These agents provide some alternative when no other options are available.
Project description:A one-year-old baby girl with one-month history of recurrent pus fluid exuding from her left preauricular sinus orifice, who failed multiple courses of surgical drainage of the abscess and persistent debridement for the wound, presented with MRSA infection. The patient was treated with linezolid for three days. Her pain and paresthesia resolved, and C-reactive protein decreased to normal.