Faculty Opinions recommendation of Arginine catabolic mobile element encoded speG abrogates the unique hypersensitivity of Staphylococcus aureus to exogenous polyamines.

Author(s):  
Rowena Matthews ◽  
Elise Hondorp
2017 ◽  
Vol 114 (49) ◽  
pp. E10596-E10604 ◽  
Author(s):  
Lena Strauß ◽  
Marc Stegger ◽  
Patrick Eberechi Akpaka ◽  
Abraham Alabi ◽  
Sebastien Breurec ◽  
...  

USA300 is a pandemic clonal lineage of hypervirulent, community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) with specific molecular characteristics. Despite its high clinical relevance, the evolutionary origin of USA300 remained unclear. We used comparative genomics of 224 temporal and spatial diverse S. aureus isolates of multilocus sequence type (ST) 8 to reconstruct the molecular evolution and global dissemination of ST8, including USA300. Analyses of core SNP diversity and accessory genome variations showed that the ancestor of all ST8 S. aureus most likely emerged in Central Europe in the mid-19th century. From here, ST8 was exported to North America in the early 20th century and progressively acquired the USA300 characteristics Panton–Valentine leukocidin (PVL), SCCmec IVa, the arginine catabolic mobile element (ACME), and a specific mutation in capsular polysaccharide gene cap5E. Although the PVL-encoding phage ϕSa2USA was introduced into the ST8 background only once, various SCCmec types were introduced to ST8 at different times and places. Starting from North America, USA300 spread globally, including Africa. African USA300 isolates have aberrant spa-types (t112, t121) and form a monophyletic group within the clade of North American USA300. Large parts of ST8 methicillin-susceptible S. aureus (MSSA) isolated in Africa represent a symplesiomorphic group of ST8 (i.e., a group representing the characteristics of the ancestor), which are rarely found in other world regions. Isolates previously discussed as USA300 ancestors, including USA500 and a “historic” CA-MRSA from Western Australia, were shown to be only distantly related to recent USA300 clones.


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.


2013 ◽  
Vol 13 (1) ◽  
pp. 100-107 ◽  
Author(s):  
Lance R. Thurlow ◽  
Gauri S. Joshi ◽  
Justin R. Clark ◽  
Jeffrey S. Spontak ◽  
Crystal J. Neely ◽  
...  

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.


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.


2009 ◽  
Vol 77 (7) ◽  
pp. 2650-2656 ◽  
Author(s):  
Christopher P. Montgomery ◽  
Susan Boyle-Vavra ◽  
Robert S. Daum

ABSTRACT USA300 has become the predominant community-associated methicillin (meticillin)-resistant Staphylococcus aureus (CA-MRSA) genetic background in most U.S. communities. The reasons for the dominance of this genetic background are unclear, but the presence of the recently identified arginine catabolic mobile element (ACME) in the USA300 genome has been advocated as one possibility. CA-MRSA clinical isolates (USA300) differing in the presence or absence of ACME and a USA300 wild-type/ACME deletion mutant pair were analyzed for in vitro expression of global regulatory genes and production of virulence factors. The virulence of these isolates was compared in rodent models of necrotizing pneumonia and skin infection. There was no significant difference in the expression of selected genes mediating virulence (hla, lukSF-PV, agr, saeRS) among the isolates tested, regardless of the presence of ACME. There was a higher abundance of α-hemolysin in culture supernatants among ACME-positive isolates than among ACME-negative isolates, but there was no significant difference in the levels of protein A. The presence of ACME was not associated with increased virulence in a rat model of necrotizing pneumonia, as assessed by mortality, in vivo bacterial survival, and severity of lung pathology. Nor was the presence of ACME associated with increased dermonecrosis in a model of skin infection. We conclude that ACME is not necessary for virulence in rodent models of CA-MRSA USA300 pneumonia or skin infection.


2013 ◽  
Vol 62 (12) ◽  
pp. 1852-1863 ◽  
Author(s):  
Mitsuyo Kawaguchiya ◽  
Noriko Urushibara ◽  
Souvik Ghosh ◽  
Osamu Kuwahara ◽  
Shigeo Morimoto ◽  
...  

Panton–Valentine leukocidine (PVL) is a distinctive virulence factor of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA), and arginine catabolic mobile element (ACME) is a staphylococcal genomic island that enhances fitness and the ability of bacterial cells to colonize on skin and mucous membranes. ACME is characteristically found in USA300, which is a predominant CA-MRSA clone [sequence type (ST) 8] in the USA and is spreading globally, and has also been detected in non-ST8 MRSA at low frequency. In Japan, spread of MRSA with PVL and/or ACME and their genetic traits have not yet been well characterized. In the present study, the prevalence and genetic diversity of PVL+/ACME+ MRSA were investigated for 422 MRSA clinical isolates collected from outpatients in northern Japan over a period of 1 year. All the isolates were genotyped for the staphylococcal cassette chromosome mec (SCCmec) and coagulase genes (coa), and screened for PVL and ACME genes. The PVL+/ACME+ isolates were studied further by genetic analysis, including single-nucleotide polymorphism (SNP) analysis based on PVL genes (lukS-PV-lukF-PV), ACME (arc and opp3 clusters) and the sarU promoter region. Among all the isolates examined, PVL genes and ACME were detected in eight (SCCmec-II, n = 1; SCCmec-IV, n = 6; SCCmec-V, n = 1) and 20 (SCCmec-II, n = 14; SCCmec-IV, n = 5; SCCmec-V, n = 1) isolates, respectively. Five isolates were found to have both PVL genes and ACME (type I), and were classified into ST8/spa-t008/agr-I/coa-IIIa, which is the same genetic traits as USA300. Fifteen PVL−/ACME+ isolates had type ΔII-ACME, belonging to either ST5 or ST764 [clonal complex (CC) 5], and spa-t001, -t002 or -t3557. All the ST8 PVL+/ACME-I+ MRSA had identical sequences of PVL genes (haplotype R) and ACME arc/opp3 clusters as those of USA300. In contrast, in the CC5 PVL−/ACME-ΔII+ MRSA, SNPs in the arc cluster were detected in 11 sites (four haplotypes), with some different profiles of virulence/resistance factors. These results indicated single clonality of ST8 PVL+/ACME-I+ MRSA and heterogeneity of CC5 PVL−/ACME-ΔII+ MRSA, and suggest their potential spread in northern Japan.


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.


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