Global Spread of the Community-Associated Methicillin-Resistant Staphylococcus aureus USA300 Latin American Variant.
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ABSTRACT:
SUBMITTER: Planet PJ
PROVIDER: S-EPMC5091374 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We aimed to determine the prevalence of MRSA colonization and examine the molecular characteristics of colonizing isolates in patients receiving hemodialysis and HIV-infected in a Colombian hospital. Patients on hemodialysis and HIV-infected were prospectively followed between July 2011 and June 2012 in Bogota, Colombia. Nasal and axillary swabs were obtained and cultured. Colonizing S. aureus isolates were identified by standard and molecular techniques. Molecular typing was performed by using pulse-field gel electrophoresis and evaluating the presence of lukF-PV/lukS-PV by PCR. A total of 29% (n = 82) of HIV-infected and 45.5% (n = 15) of patients on hemodialysis exhibited S. aureus colonization. MSSA/MRSA colonization was observed in 28% and 3.6% of the HIV patients, respectively and in 42.4% and 13.3% of the hemodialysis patients, respectively. Staphylococcal cassette chromosome mec typing showed that four MRSA isolates harbored the type IV cassette, and one type I. In the hemodialysis group, two MRSA isolates were classified as belonging to the USA300-LV genetic lineage. Conversely, in the HIV infected group, no colonizing isolates belonging to the USA300-Latin American Variant (UDA300-LV) lineage were identified. Colonizing isolates recovered from the HIV-infected group belonged to the prevalent hospital-associated clones circulating in Latin America (Chilean [n = 1] and Pediatric [n = 2]). The prevalence of MRSA colonization in the study groups was 3.6% (HIV) and 13.3% (hemodialysis). Surveillance programs should be implemented in this group of patients in order to understand the dynamics of colonization and infection in high-risk patients.
| S-EPMC4608721 | biostudies-literature
Project description:UnlabelledCommunity-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized worldwide during the 1990s; in less than a decade, several genetically distinct CA-MRSA lineages carrying Panton-Valentine leukocidin genes have emerged on every continent. Most notably, in the United States, the sequence type 18-IV (ST8-IV) clone known as USA300 has become highly prevalent, outcompeting methicillin-susceptible S. aureus (MSSA) and other MRSA strains in both community and hospital settings. CA-MRSA bacteria are much less prevalent in Europe, where the European ST80-IV European CA-MRSA clone, USA300 CA-MRSA strains, and other lineages, such as ST22-IV, coexist. The question that arises is whether the USA300 CA-MRSA present in Europe (i) was imported once or on very few occasions, followed by a broad geographic spread, anticipating an increased prevalence in the future, or (ii) derived from multiple importations with limited spreading success. In the present study, we applied whole-genome sequencing to a collection of French USA300 CA-MRSA strains responsible for sporadic cases and micro-outbreaks over the past decade and United States ST8 MSSA and MRSA isolates. Genome-wide phylogenetic analysis demonstrated that the population structure of the French isolates is the product of multiple introductions dating back to the onset of the USA300 CA-MRSA clone in North America. Coalescent-based demography of the USA300 lineage shows that a strong expansion occurred during the 1990s concomitant with the acquisition of the arginine catabolic mobile element and antibiotic resistance, followed by a sharp decline initiated around 2008, reminiscent of the rise-and-fall pattern previously observed in the ST80 lineage. A future expansion of the USA300 lineage in Europe is therefore very unlikely.ImportanceTo trace the origin, evolution, and dissemination pattern of the USA300 CA-MRSA clone in France, we sequenced a collection of strains of this lineage from cases reported in France in the last decade and compared them with 431 ST8 strains from the United States. We determined that the French CA-MRSA USA300 sporadic and micro-outbreak isolates resulted from multiple independent introductions of the USA300 North American lineage. At a global level, in the transition from an MSSA lineage to a successful CA-MRSA clone, it first became resistant to multiple antibiotics and acquired the arginine catabolic mobile element and subsequently acquired resistance to fluoroquinolones, and these two steps were associated with a dramatic demographic expansion. This expansion was followed by the current stabilization and expected decline of this lineage. These findings highlight the significance of horizontal gene acquisitions and point mutations in the success of such disseminated clones and illustrate their cyclic and sporadic life cycle.
| S-EPMC4752609 | biostudies-literature
Project description:The USA300 North American epidemic (USA300-NAE) clone of methicillin-resistant Staphylococcus aureus has caused a wave of severe skin and soft tissue infections in the United States since it emerged in the early 2000s, but its geographic origin is obscure. Here we use the population genomic signatures expected from the serial founder effects of a geographic range expansion to infer the origin of USA300-NAE and identify polymorphisms associated with its spread. Genome sequences from 357 isolates from 22 U.S. states and territories and seven other countries are compared. We observe two significant signatures of range expansion, including decreases in genetic diversity and increases in derived allele frequency with geographic distance from the Pennsylvania region. These signatures account for approximately half of the core nucleotide variation of this clone, occur genome wide, and are robust to heterogeneity in temporal sampling of isolates, human population density, and recombination detection methods. The potential for positive selection of a gyrA fluoroquinolone resistance allele and several intergenic regions, along with a 2.4 times higher recombination rate in a resistant subclade, is noted. These results are the first to show a pattern of genetic variation that is consistent with a range expansion of an epidemic bacterial clone, and they highlight a rarely considered but potentially common mechanism by which genetic drift may profoundly influence bacterial genetic variation.IMPORTANCE The process of geographic spread of an origin population by a series of smaller populations can result in distinctive patterns of genetic variation. We detect these patterns for the first time with an epidemic bacterial clone and use them to uncover the clone's geographic origin and variants associated with its spread. We study the USA300 clone of methicillin-resistant Staphylococcus aureus, which was first noticed in the early 2000s and subsequently became the leading cause of skin and soft tissue infections in the United States. The eastern United States is the most likely origin of epidemic USA300. Relatively few variants, which include an antibiotic resistance mutation, have persisted during this clone's spread. Our study suggests that an early chapter in the genetic history of this epidemic bacterial clone was greatly influenced by random subsampling of isolates during the clone's geographic spread.
| S-EPMC5750399 | biostudies-literature
Project description:In the United States, methicillin-resistant Staphylococcus aureus (MRSA) with the USA300 pulsed-field gel electrophoresis type causes most community-associated MRSA infections and is an increasingly common cause of health care-associated MRSA infections. USA300 probably emerged during the early 1990s. To assess the spatiotemporal diffusion of USA300 MRSA and USA100 MRSA throughout the United States, we systematically reviewed 354 articles for data on 33,543 isolates, of which 8,092 were classified as USA300 and 2,595 as USA100. Using the biomedical literature as a proxy for USA300 prevalence among genotyped MRSA samples, we found that USA300 was isolated during 2000 in several states, including California, Texas, and midwestern states. The geographic mean center of USA300 MRSA then shifted eastward from 2000 to 2013. Analyzing genotyping studies enabled us to track the emergence of a new, successful MRSA type in space and time across the country.
| S-EPMC4622244 | biostudies-literature
Project description:BackgroundCommunity-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a significant bacterial pathogen that poses considerable clinical and public health challenges. The majority of the CA-MRSA disease burden consists of skin and soft tissue infections (SSTI) not associated with significant morbidity; however, CA-MRSA also causes severe, invasive infections resulting in significant morbidity and mortality. The broad range of disease severity may be influenced by bacterial genetic variation.ResultsWe sequenced the complete genomes of 36 CA-MRSA clinical isolates from the predominant North American community acquired clonal type USA300 (18 SSTI and 18 severe infection-associated isolates). While all 36 isolates shared remarkable genetic similarity, we found greater overall time-dependent sequence diversity among SSTI isolates. In addition, pathway analysis of non-synonymous variations revealed increased sequence diversity in the putative virulence genes of SSTI isolates.ConclusionsHere we report the first whole genome survey of diverse clinical isolates of the USA300 lineage and describe the evolution of the pathogen over time within a defined geographic area. The results demonstrate the close relatedness of clinically independent CA-MRSA isolates, which carry implications for understanding CA-MRSA epidemiology and combating its spread.
| S-EPMC3598774 | biostudies-literature
Project description:Little is known about the expression of methicillin-resistant Staphylococcus aureus (MRSA) genes during infection conditions. Here, we described the transcriptome of the clinical MRSA strain USA300 derived from human cutaneous abscesses, and compared it with USA300 bacteria derived from infected kidneys in a mouse model. Remarkable similarity between the transcriptomes allowed us to identify genes encoding multiple proteases and toxins, and iron- and peptide-transporter molecules, which are upregulated in both infections and are likely important for establishment of infection. We also showed that disruption of the global transcriptional regulators agr and sae prevents in vivo upregulation of many toxins and proteases, protecting mice from lethal infection dose, and hinting at the role of these transcriptional regulators in the pathology of MRSA infection.
2015-10-16 | GSE73821 | GEO
Project description:In a community, it is unknown what factors account for transmission of methicillin-resistant Staphylococcus aureus (MRSA). We integrated whole genome sequencing (WGS) and epidemiologic data to identify factors associated with MRSA transmission networks in an urban community.WGS was performed on colonizing USA300 MRSA isolates from 74 individuals within 72 hours of admission to a public hospital in Chicago, IL. Single nucleotide variants (SNVs) were used to reconstruct the phylogeny of sequenced isolates, and epidemiologic data was overlaid to identify factors associated with transmission networks.The maximum within-patient SNV difference for an individual with multisite colonization was 41 SNVs, with no systematic divergence among body sites. We observed a minimum of 7 SNVs and maximum of 153 SNVs between isolates from different individuals. We identified 4 pairs of individuals whose isolates were within 40 SNVs of each other. Putting our isolates in the context of previously sequenced USA300 isolates from other communities, we identified a 13-member group and two 4-member groups that represent samples from putative local transmission networks. Individuals in these groups were more likely to be African American, to be human immunodeficiency virus-infected, to reside in high detainee release areas, and to be current users of illicit drugs.Using WGS, we observed potential transmission networks in an urban community and that certain epidemiologic factors were associated with inclusion in these networks. Future work with contact tracing and advanced molecular diagnostics may allow for identification of MRSA "epicenters" in the community where interventions can be targeted.
| S-EPMC4678108 | biostudies-literature
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) USA300 isolates have been recognized globally, not only in community but also in healthcare settings. USA300 isolates were initially resistant only to methicillin, but resistance to non-?-lactams has emerged with time. To evaluate the prevalence and antimicrobial susceptibility of USA300 isolates in Stockholm, we conducted a nine-year retrospective study. Of 5359 consecutive MRSA cases in Stockholm, isolates from 285 cases were USA300 strains according to the pulsed-field gel electrophoresis pattern. Of these cases, repeated isolates with altered antibiotic resistance patterns were observed in six individuals. Therefore, antimicrobial susceptibility testing was performed on totally 291 isolates. To study the phylogenetic relatedness of isolates in transmission events and genomic resistance traits, 35 isolates were further studied by whole genome sequencing (WGS). The incidence of MRSA was increased from 17.6 per 100,000 inhabitants in 2008 to 37.3 per 100,000 inhabitants in 2016, while the proportion of USA300 cases declined from 6.6% in 2008 to 2.6% in 2016. Among the USA300 isolates, 73.5% were community-associated, 21.3% healthcare-associated, and 5.2% had unknown acquisition. The highest resistance rate among non-?-lactams was found in erythromycin (86%), followed by fluoroquinolones (68-69%). 57% of the isolates were resistant to both erythromycin and fluoroquinolone. Simultaneous resistance to four non-?-lactam antibiotic classes was found in six isolates. Four isolates were susceptible to all non-?-lactam antibiotics. Ceftaroline, daptomycin, linezolid, mupirocin, rifampicin, teicoplanin, telavancin, trimethoprim-sulfamethoxazole and vancomycin retained full activity in the study. WGS analysis indicated that isolates from an outbreak were phylogenetically closely related. In conclusion, USA300 MRSA isolates in Stockholm have neither been limited to the community setting, nor remained susceptible to non-?-lactam agents. WGS is becoming a useful tool in tracing transmission events. The results herein provide the most up-to-date and comprehensive information regarding status of USA300 strains in this geographic area.
| S-EPMC6221263 | biostudies-literature
Project description:Subinhibitory concentrations of the neuroleptic drug thioridazine (TDZ) are well-known to enhance the killing of methicillin-resistant Staphylococcus aureus (MRSA) by ?-lactam antibiotics, however, the mechanism underlying the synergy between TDZ and ?-lactams is not fully understood. In the present study, we have examined the effect of a subinhibitory concentration of TDZ on antimicrobial resistance, the global transcriptome, and the cell wall composition of MRSA USA300. We show that TDZ is able to sensitize the bacteria to several classes of antimicrobials targeting the late stages of peptidoglycan (PGN) synthesis. Furthermore, our microarray analysis demonstrates that TDZ modulates the expression of genes encoding membrane and surface proteins, transporters, and enzymes involved in amino acid biosynthesis. Interestingly, resemblance between the transcriptional profile of TDZ treatment and the transcriptomic response of S. aureus to known inhibitors of cell wall synthesis suggests that TDZ disturbs PGN biosynthesis at a stage that precedes transpeptidation by penicillin-binding proteins (PBPs). In support of this notion, dramatic changes in the muropeptide profile of USA300 were observed following growth in the presence of TDZ, indicating that TDZ can interfere with the formation of the pentaglycine branches. Strikingly, the addition of glycine to the growth medium relieved the effect of TDZ on the muropeptide profile. Furthermore, exogenous glycine offered a modest protective effect against TDZ-induced ?-lactam sensitivity. We propose that TDZ exposure leads to a shortage of intracellular amino acids, including glycine, which is required for the production of normal PGN precursors with pentaglycine branches, the correct substrate of S. aureus PBPs. Collectively, this work demonstrates that TDZ has a major impact on the cell wall biosynthesis pathway in S. aureus and provides new insights into how MRSA may be sensitized towards ?-lactam antibiotics.
| S-EPMC3656896 | biostudies-literature
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) pulsed-field type (PFT) USA300 causes skin and soft tissue infections in military recruits and invasive disease in hospitals. Chlorhexidine gluconate (CHG) is used to reduce MRSA colonization and infection. The impact of CHG on the molecular epidemiology of MRSA is not known.To evaluate the impact of 2% CHG-impregnated cloths on the molecular epidemiology of MRSA colonization.Cluster-randomized, double-blind, controlled trial.Marine Officer Candidate School, Quantico, Virginia, in 2007.Military recruits.Thrice-weekly application of CHG-impregnated or control (Comfort Bath; Sage) cloths over the entire body.Baseline and serial (every 2 weeks) nasal and/or axillary swab samples were assessed for MRSA colonization. Molecular analysis was performed with pulsed-field gel electrophoresis.During training, 77 subjects (4.9%) acquired MRSA, 26 (3.3%) in the CHG group and 51 (6.5%) in the control group (P=.004). When analyzed for PFT, 24 subjects (3.1%) in the control group but only 6 subjects (0.8%) in the CHG group (P=.001) had USA300. Of the 167 colonizing isolates recovered from 77 subjects, 99 were recovered from the control group, including USA300 (40.4%), USA800 (38.4%), USA1000 (12.1%), and USA100 (6.1%), and 68 were recovered from the CHG group, including USA800 (51.5%), USA100 (23.5%), and USA300 (13.2%).CHG decreased the transmission of MRSA--more specifically, USA300--among military recruits. In addition, USA300 and USA800 outcompeted other MRSA PFTs at incident colonization. Future studies should evaluate the broad-based use of CHG to decrease transmission of USA300 in hospital settings.
| S-EPMC5824645 | biostudies-literature