scholarly journals Emergence of the Epidemic Methicillin-Resistant Staphylococcus aureus Strain USA300 Coincides with Horizontal Transfer of the Arginine Catabolic Mobile Element and speG-mediated Adaptations for Survival on Skin

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Paul J. Planet ◽  
Samuel J. LaRussa ◽  
Ali Dana ◽  
Hannah Smith ◽  
Amy Xu ◽  
...  

ABSTRACTThe arginine catabolic mobile element (ACME) is the largest genomic region distinguishing epidemic USA300 strains of methicillin-resistantStaphylococcus aureus(MRSA) from otherS. aureusstrains. However, the functional relevance of ACME to infection and disease has remained unclear. Using phylogenetic analysis, we have shown that the modular segments of ACME were assembled into a single genetic locus inStaphylococcus epidermidisand then horizontally transferred to the common ancestor of USA300 strains in an extremely recent event. Acquisition of one ACME gene,speG, allowed USA300 strains to withstand levels of polyamines (e.g., spermidine) produced in skin that are toxic to other closely relatedS. aureusstrains.speG-mediated polyamine tolerance also enhanced biofilm formation, adherence to fibrinogen/fibronectin, and resistance to antibiotic and keratinocyte-mediated killing. We suggest that these properties gave USA300 a major selective advantage during skin infection and colonization, contributing to the extraordinary evolutionary success of this clone.IMPORTANCEOver the past 15 years, methicillin-resistantStaphylococcus aureus(MRSA) has become a major public health problem. It is likely that adaptations in specific MRSA lineages (e.g., USA300) drove the spread of MRSA across the United States and allowed it to replace other, less-virulentS. aureusstrains. We suggest that one major factor in the evolutionary success of MRSA may have been the acquisition of a gene (speG) that allowsS. aureusto evade the toxicity of polyamines (e.g., spermidine and spermine) that are produced in human skin. Polyamine tolerance likely gave MRSA multiple fitness advantages, including the formation of more-robust biofilms, increased adherence to host tissues, and resistance to antibiotics and killing by human skin cells.

2011 ◽  
Vol 55 (5) ◽  
pp. 1896-1905 ◽  
Author(s):  
Anna C. Shore ◽  
Angela S. Rossney ◽  
Orla M. Brennan ◽  
Peter M. Kinnevey ◽  
Hilary Humphreys ◽  
...  

ABSTRACTThe arginine catabolic mobile element (ACME) is prevalent among methicillin-resistantStaphylococcus aureus(MRSA) isolates of sequence type 8 (ST8) and staphylococcal chromosomal cassettemec(SCCmec) type IVa (USA300) (ST8-MRSA-IVa isolates), and evidence suggests that ACME enhances the ability of ST8-MRSA-IVa to grow and survive on its host. ACME has been identified in a small number of isolates belonging to other MRSA clones but is widespread among coagulase-negative staphylococci (CoNS). This study reports the first description of ACME in two distinct strains of the pandemic ST22-MRSA-IV clone. A total of 238 MRSA isolates recovered in Ireland between 1971 and 2008 were investigated for ACME using a DNA microarray. Twenty-three isolates (9.7%) were ACME positive, and all were either MRSA genotype ST8-MRSA-IVa (7/23, 30%) or MRSA genotype ST22-MRSA-IV (16/23, 70%). Whole-genome sequencing and comprehensive molecular characterization revealed the presence of a novel 46-kb ACME and staphylococcal chromosomal cassettemec(SCCmec) composite island (ACME/SCCmec-CI) in ST22-MRSA-IVh isolates (n= 15). This ACME/SCCmec-CI consists of a 12-kb DNA region previously identified in ACME type II inS. epidermidisATCC 12228, a truncated copy of the J1 region of SCCmectype I, and a complete SCCmectype IVh element. The composite island has a novel genetic organization, with ACME located withinorfXand SCCmeclocated downstream of ACME. One PVL locus-positive ST22-MRSA-IVa isolate carried ACME located downstream of SCCmectype IVa, as previously described in ST8-MRSA-IVa. These results suggest that ACME has been acquired by ST22-MRSA-IV on two independent occasions. At least one of these instances may have involved horizontal transfer and recombination events between MRSA and CoNS. The presence of ACME may enhance dissemination of ST22-MRSA-IV, an already successful MRSA clone.


2017 ◽  
Vol 84 (2) ◽  
Author(s):  
Samantha J. Hau ◽  
Steven Kellner ◽  
Kirsten C. Eberle ◽  
Ursula Waack ◽  
Susan L. Brockmeier ◽  
...  

ABSTRACT Staphylococcus aureus is part of the nasal microbiome of many humans and has become a significant public health burden due to infections with antibiotic-resistant strains, including methicillin-resistant S. aureus (MRSA) strains. Several lineages of S. aureus, including MRSA, are found in livestock species and can be acquired by humans through contact with animals. These livestock-associated MRSA (LA-MRSA) isolates raise public health concerns because of the potential for livestock to act as reservoirs for MRSA outside the hospital setting. In the United States, swine harbor a mixed population of LA-MRSA isolates, with the sequence type 398 (ST398), ST9, and ST5 lineages being detected. LA-MRSA ST5 isolates are particularly concerning to the public health community because, unlike the isolates in the ST398 and ST9 lineages, isolates in the ST5 lineage are a significant cause of human disease in both the hospital and community settings globally. The ability of swine-associated LA-MRSA ST5 isolates to adhere to human keratinocytes in vitro was investigated, and the adherence genes harbored by these isolates were evaluated and compared to those in clinical MRSA ST5 isolates from humans with no swine contact. The two subsets of isolates adhered equivalently to human keratinocytes in vitro and contained an indistinguishable complement of adherence genes that possessed a high degree of sequence identity. Collectively, our data indicate that, unlike LA-MRSA ST398 isolates, LA-MRSA ST5 isolates do not exhibit a reduced genotypic or phenotypic capacity to adhere to human keratinocytes. IMPORTANCE Our data indicate that swine-associated livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) ST5 isolates are as capable of adhering to human skin and have the same genetic potential to adhere as clinical MRSA ST5 isolates from humans. This suggests that humans in contact with livestock have the potential to become colonized with LA-MRSA ST5 isolates; however, the genes that contribute to the persistence of S. aureus on human skin were absent in LA-MRSA ST5 isolates. The data presented here are important evidence in evaluating the potential risks that LA-MRSA ST5 isolates pose to humans who come into contact with livestock.


2015 ◽  
Vol 53 (8) ◽  
pp. 2486-2491 ◽  
Author(s):  
Michael Z. David ◽  
Mary Ellen Acree ◽  
Julia J. Sieth ◽  
Dave J. Boxrud ◽  
Ginette Dobbins ◽  
...  

Widespread infections with community-associated (CA) methicillin-resistantStaphylococcus aureus(MRSA) have occurred in the United States with the dissemination of the USA300 strain beginning in 2000. We examined 105 isolates obtained from children treated at the University of Chicago from 1994 to 1997 (75 methicillin-susceptibleS. aureus[MSSA] and 30 MRSA isolates) in order to investigate for possible evidence of USA300 during this period. Infections were defined epidemiologically based on medical record review. The isolates underwent multilocus sequence typing (MLST), as well as assays for the Panton-Valentine leukocidin (PVL) genes, the protein A gene (spa), andarcAandopp3, proxy markers for the arginine catabolic mobile element (ACME), characteristic of USA300 MRSA. MRSA isolates also underwent staphylococcal cassette chromosomemec(SCCmec) typing and pulsed-field gel electrophoresis (PFGE) subtyping. MSSA isolates belonged to 17 sequence type (ST) groups. The 12 epidemiologically defined CA-MRSA infection isolates were either ST1 (n= 4) or ST8 (n= 8). They belonged to 3 different PFGE types: USA100 (n= 1), USA400 (n= 5), and USA500 (n= 6). Among the CA-MRSA infection isolates, 8 (67%) were PVL+. None of the MRSA or MSSA isolates containedarcAoropp3. Only one MRSA isolate was USA300 by PFGE. This was a health care-associated (HA) MRSA isolate, negative for PVL, that carried SCCmectype II. USA300 with its characteristic features was not identified in the collection from the years 1994 to 1997.


2020 ◽  
Vol 8 (2) ◽  
pp. 275 ◽  
Author(s):  
Kaiyu Wu ◽  
John Conly ◽  
Jo-Ann McClure ◽  
Habib A. Kurwa ◽  
Kunyan Zhang

USA300 is a predominant community-associated methicillin-resistant Staphylococcus aureus strain which carries an arginine catabolic mobile element (ACME). ACME contains potential virulence factors including an arginine deiminase (arc) pathway and an oligopeptide permease (opp-3) system, which are proposed to play a role in bacterial virulence and transmission. However, the role of ACME in evolution and pathogenicity of USA300 remains to be elucidated. ACME and arcA deletion mutants were created by allelic replacement from a USA300 clinical isolate. By comparing wild type and isogenic ACME deletion USA300 strains, ACME was shown not to contribute to bacterial survival on plastic surfaces, and mouse skin surfaces. ACME did not contribute to bacterial virulence in cell invasion and cytotoxicity assays, invertebrate killing assays and a mouse skin infection model. Wild-type ACME negative USA300 clinical isolates showed similar associations with invasive anatomic sites as ACME positive isolates. Our experiments also demonstrated that ACME can spontaneously excise from the bacterial chromosome to generate an ACME deletion strain at a low frequency. Our results do not support that the ACME element alone is a significant factor in the transmission and virulence of USA300 strain, and ACME may have been coincidently incorporated into the genome of USA300.


mBio ◽  
2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Philippe Glaser ◽  
Patrícia Martins-Simões ◽  
Adrien Villain ◽  
Maxime Barbier ◽  
Anne Tristan ◽  
...  

ABSTRACT Community-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. IMPORTANCE To 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.


2016 ◽  
Vol 60 (5) ◽  
pp. 3119-3122 ◽  
Author(s):  
Noriko Urushibara ◽  
Mitsuyo Kawaguchiya ◽  
Mayumi Onishi ◽  
Keiji Mise ◽  
Meiji Soe Aung ◽  
...  

ABSTRACTTwenty-two of 1,103 methicillin-resistantStaphylococcus aureus(MRSA) isolates containing the type II staphylococcal cassette chromosomemecelement (SCCmec) (collected in Hokkaido, Japan, from 2008 to 2011) harbored the arginine catabolic mobile element (ACME). Five genetic variations were identified in the ACME-staphylococcal cassette chromosomemeccomposite islands, 66 to 79 kb in size. The percentage of ACME carriage temporally increased from 0.85% to 4.5% in parallel with the emergence of shorter variants (66 to 72 kb). Shorter variants may have a selective advantage and accelerate the dissemination of ACME in Japanese MRSA.


2012 ◽  
Vol 56 (6) ◽  
pp. 3380-3383 ◽  
Author(s):  
B. A. Espedido ◽  
J. A. Steen ◽  
T. Barbagiannakos ◽  
J. Mercer ◽  
D. L. Paterson ◽  
...  

ABSTRACTApproximately 39% of methicillin-resistantStaphylococcus aureus(MRSA) sequence type 239 (ST239)-like bloodstream isolates from Liverpool Hospital (obtained between 1997 and 2008) carry an arginine catabolic mobile element (ACME). Whole-genome sequencing revealed that an ACME II variant is located betweenorfXand SCCmecIII, and based on pulsed-field gel electrophoresis patterns and temporal relationships of all ST239-like isolates (n= 360), ACME carriage may have contributed to subpulsotype strain replacement.


2019 ◽  
Vol 57 (11) ◽  
Author(s):  
Fred C. Tenover ◽  
Isabella A. Tickler ◽  
Victoria M. Le ◽  
Scott Dewell ◽  
Rodrigo E. Mendes ◽  
...  

ABSTRACT Molecular diagnostic tests can be used to provide rapid identification of staphylococcal species in blood culture bottles to help improve antimicrobial stewardship. However, alterations in the target nucleic acid sequences of the microorganisms or their antimicrobial resistance genes can lead to false-negative results. We determined the whole-genome sequences of 4 blood culture isolates of Staphylococcus aureus and 2 control organisms to understand the genetic basis of genotype-phenotype discrepancies when using the Xpert MRSA/SA BC test (in vitro diagnostic medical device [IVD]). Three methicillin-resistant S. aureus (MRSA) isolates each had a different insertion of a genetic element in the staphylococcal cassette chromosome (SCCmec)-orfX junction region that led to a misclassification as methicillin-susceptible S. aureus (MSSA). One strain contained a deletion in spa, which produced a false S. aureus-negative result. A control strain of S. aureus that harbored an SCCmec element but no mecA (an empty cassette) was correctly called MSSA by the Xpert test. The second control contained an SCCM1 insertion. The updated Xpert MRSA/SA BC test successfully detected both spa and SCCmec variants of MRSA and correctly identified empty-cassette strains of S. aureus as MSSA. Among a sample of 252 MSSA isolates from the United States and Europe, 3.9% contained empty SCCmec cassettes, 1.6% carried SCCM1, <1% had spa deletions, and <1% contained SCCmec variants other than those with SCCM1. These data suggest that genetic variations that may interfere with Xpert MRSA/SA BC test results remain rare. Results for all the isolates were correct when tested with the updated assay.


2019 ◽  
Vol 8 (23) ◽  
Author(s):  
Ting Lei ◽  
Ying Zhang ◽  
Junshu Yang ◽  
Kevin Silverstein ◽  
Yinduo Ji

The hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) strain WCUH29 has been intensively and widely used as a model system for identification and evaluation of novel antibacterial targets and pathogenicity. In this announcement, we report the complete genome sequence of HA-MRSA WCUH29 (NCIMB 40771).


mBio ◽  
2012 ◽  
Vol 3 (3) ◽  
Author(s):  
Veronica N. Kos ◽  
Christopher A. Desjardins ◽  
Allison Griggs ◽  
Gustavo Cerqueira ◽  
Andries Van Tonder ◽  
...  

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistantS. aureus(VRSA) infection in the United States—all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift indprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition.IMPORTANCEInvasive methicillin-resistantStaphylococcus aureus(MRSA) infection now ranks among the leading causes of death in the United States. Vancomycin is a key last-line bactericidal drug for treating these infections. However, since 2002, vancomycin resistance has entered this species. Of the now 12 cases of vancomycin-resistantS. aureus(VRSA), each was believed to represent a new acquisition of the vancomycin-resistant transposon Tn1546from enterococcal donors. All acquisitions of Tn1546so far have occurred in MRSA strains of the clonal cluster 5 genetic background, the most common hospital lineage causing hospital-acquired MRSA infection. To understand the nature of these strains, we determined and examined the nucleotide sequences of the genomes of all available VRSA. Genome comparison identified candidate features that position strains of this lineage well for acquiring resistance to antibiotics in mixed infection.


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