scholarly journals The Arginine Catabolic Mobile Element Is Not Associated with Enhanced Virulence in Experimental Invasive Disease Caused by the Community-Associated Methicillin-Resistant Staphylococcus aureus USA300 Genetic Background

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.

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Patrycja Ogonowska ◽  
Yolanda Gilaberte ◽  
Wioletta Barańska-Rybak ◽  
Joanna Nakonieczna

Atopic dermatitis (AD) patients are massively colonized with Staphylococcus aureus (S. aureus) in lesional and non-lesional skin. A skin infection may become systemic if left untreated. Of interest, the incidence of multi-drug resistant S. aureus (MRSA) in AD patients is higher as compared to a healthy population, which makes treatment even more challenging. Information on the specific genetic background of S. aureus accompanying and/or causing AD flares would be of great importance in terms of possible treatment option development. In this review, we summarized the data on the prevalence of S. aureus in general in AD skin, and the prevalence of specific clones that might be associated with flares of eczema. We put our special interest in the presence and role of staphylococcal enterotoxins as important virulence factors in the epidemiology of AD-derived S. aureus. Also, we summarize the present and potentially useful future anti-staphylococcal treatment.


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.


2011 ◽  
Vol 55 (6) ◽  
pp. 2818-2823 ◽  
Author(s):  
Dae Sun Jo ◽  
Christopher P. Montgomery ◽  
Shaohui Yin ◽  
Susan Boyle-Vavra ◽  
Robert S. Daum

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are major pathogens causing infections of the skin and soft tissues and more serious, life-threatening diseases, including sepsis and necrotizing pneumonia. ThevraSRoperon encodes the key regulatory system that modulates the stress response ofS. aureuselicited upon exposure to cell wall antibiotics. Mutation ofvraSandvraRresults in decreased oxacillin resistancein vitro. We investigated the effect of oxacillin treatment in experimental models employing a clinical USA300 MRSA strain (strain 923) and an isogenicvraSRdeletion mutant (strain 923-M23). In a murine model ofS. aureusnecrotizing pneumonia, animals were treated with oxacillin, beginning 15 min after inoculation. Among mice infected with mutant strain 923-M23, oxacillin treatment significantly improved survival compared with saline treatment, whereas oxacillin treatment had no effect in mice infected with strain 923. Similarly, treatment with oxacillin decreased the bacterial burden among animals infected with strain 923-M23 but not among animals infected with strain 923. In a murine skin infection model, oxacillin eliminated the development of dermonecrosis among 923-M23-infected mice and decreased the bacterial burden in the lesions, but not among strain 923-infected mice. We conclude that deletion of thevraSRoperon allowed an oxacillin regimen to be effective in murine models of MRSA pneumonia and skin infection. These findings provide proof-of-principle for development of a new antibiotic that could restore the usefulness of oxacillin against MRSA by inhibiting VraS or VraR.


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