Project description:Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious global problem, with considerable impact on patients and substantial health care costs. This systematic review provides an overview on the clonal diversity of MRSA, as well as the prevalence of Panton-Valentine leukocidin (PVL)-positive MRSA in Africa. A search on the molecular characterization of MRSA in Africa was conducted by two authors using predefined terms. We screened for articles published in English and French through to October 2014 from five electronic databases. A total of 57 eligible studies were identified. Thirty-four reports from 15 countries provided adequate genotyping data. CC5 is the predominant clonal complex in the healthcare setting in Africa. The hospital-associated MRSA ST239/ST241-III [3A] was identified in nine African countries. This clone was also described with SCCmec type IV [2B] in Algeria and Nigeria, and type V [5C] in Niger. In Africa, the European ST80-IV [2B] clone was limited to Algeria, Egypt and Tunisia. The clonal types ST22-IV [2B], ST36-II [2A], and ST612-IV [2B] were only reported in South Africa. No clear distinctions were observed between MRSA responsible for hospital and community infections. The community clones ST8-IV [2B] and ST88-IV [2B] were reported both in the hospital and community settings in Angola, Cameroon, Gabon, Ghana, Madagascar, Nigeria, and São Tomé and Príncipe. The proportion of PVL-positive MRSA carriage and/or infections ranged from 0.3 to 100% in humans. A number of pandemic clones were identified in Africa. Moreover, some MRSA clones are limited to specific countries or regions. We strongly advocate for more surveillance studies on MRSA in Africa.
Project description:Resistance to methicillin in Staphylococcus aureus is caused primarily by the mecA gene, which is carried on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec). Horizontal transfer of this element is supposed to be an important factor in the emergence of new clones of methicillin-resistant Staphylococcus aureus (MRSA) but has been rarely observed in real time. In 2012, an outbreak occurred involving a health care worker (HCW) and three patients, all carrying a fusidic acid-resistant MRSA strain. The husband of the HCW was screened for MRSA carriage, but only a methicillin-susceptible S. aureus (MSSA) strain, which was also resistant to fusidic acid, was detected. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing showed that both the MSSA and MRSA isolates were MT4053-MC0005. This finding led to the hypothesis that the MSSA strain acquired the SCCmec and subsequently caused an outbreak. To support this hypothesis, next-generation sequencing of the MSSA and MRSA isolates was performed. This study showed that the MSSA isolate clustered closely with the outbreak isolates based on whole-genome multilocus sequence typing and single-nucleotide polymorphism (SNP) analysis, with a genetic distance of 17 genes and 44 SNPs, respectively. Remarkably, there were relatively large differences in the mobile genetic elements in strains within and between individuals. The limited genetic distance between the MSSA and MRSA isolates in combination with a clear epidemiologic link supports the hypothesis that the MSSA isolate acquired a SCCmec and that the resulting MRSA strain caused an outbreak.
Project description:One known and three new potent, selective, and nontoxic anti-MRSA metabolites, kaempferol 3-O-alpha-l-(2'',3''-di-E-p-coumaroyl)rhamnoside (1) (IC(50) 2.0 microg/mL), kaempferol 3-O-alpha-l-(2''-E-p-coumaroyl-3''-Z-p-coumaroyl)rhamnoside (2) (IC(50) 0.8 microg/mL), kaempferol 3-O-alpha-l-(2''-Z-p-coumaroyl-3''-E-p-coumaroyl)rhamnoside (3) (IC(50) 0.7 microg/mL), and kaempferol 3-O-alpha-l-(2'',3''-di-Z-p-coumaroyl)rhamnoside (4) (IC(50) 0.4 microg/mL), were isolated from the leaves of the common American sycamore, Platanus occidentalis. Compounds 2-4 are new. Due to the unusual selectivity, potency, and safety of the pure compounds and the semipure glycoside mixture against MRSA, it is clear that this represents a viable class of inhibitors to prevent growth of MRSA on surfaces and systemically.
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:An induced stringent response, which is established by an increased level of (p)ppGpp, is required for the expression of ?-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA). However, it is not clear whether RSH (enzyme mediating stringent response to amino acid starvation) or small alarmone synthetases (SASs) are involved in the maintenance of (p)ppGpp level in response to ?-lactams. Since the S. aureus genome encodes two active SASs (RelP and RelQ), their contribution to the expression of ?-lactam resistance in MRSA was investigated. It was determined that relQ deletion renders community-associated MRSA (CA-MRSA) sensitive to ?-lactams by negatively affecting the expression of mecA, and induction of (p)ppGpp synthesis by mupirocin bypasses the requirement of relQ for the expression of high-level ?-lactam resistance. Surprisingly, relP deletion increased the level of ?-lactam resistance. Such contradictory observations could be attributed to the fact that relQ promoter is ~5-fold stronger than the relP and is induced by oxacillin as well as deletion of either of the SASs, while relP promoter responds only to oxacillin. The stronger promoter activity of relQ, coupled with the inducibility of the relQ promoter in response to the lack of relP, results in efficient expression of relQ in the relP-deleted background. This positively affects mecA expression and renders the ?relP strain highly resistant. These findings indicate an important role for RelQ in the expression of high-level ?-lactam resistance in MRSA.