Community-Associated Methicillin-Resistant Staphylococcus aureus Case Studies

Sowash, Madeleine; Uhlemann, Anne‐Catrin

doi:10.1007/978-1-62703-664-1_2

Cited by 50 publications

(31 citation statements)

References 186 publications

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“…aureus is the second-most-common pathogen recovered in nosocomial bloodstream infections in the United States, and emergent USA300 strains in particular are reported to cause the majority of complicated skin and soft-tissue infections (33)(34)(35)(36). Despite sensitivity to antibiotics, complicated S. aureus infections still have high mortality and treatment failure rates (37,38).…”

Section: Discussionmentioning

confidence: 99%

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

et al. 2014

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SEl-K is commonly present in more than half of all Staphylococcus aureus clinical isolates and is present in almost all USA300 community-acquired methicillin-resistant S. aureus (CA-MRSA) isolates. Sequencing of the sel-k gene in over 20 clinical isolates and comparative analysis with all 14 published sel-k sequences indicate that there are at least 6 variants of the sel-k gene, including one that is conserved among all examined USA300 strains. Additionally, we have developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) that specifically detects and measures SEl-K protein in culture supernatants and biological fluids. Quantification of in vitro SEl-K secretion by various S. aureus isolates using this novel capture ELISA revealed detectable amounts of SEl-K secretion by all isolates, with the highest secretion levels being exhibited by MRSA strains that coexpress SEB. In vivo secretion was measured in a murine thigh abscess model, where similar levels of SEl-K accumulation were noted regardless of whether the infecting strain exhibited high or low secretion of SEl-K in vitro. We conclude that SEl-K is commonly expressed in the setting of staphylococcal infection, in significant amounts. SEl-K should be further explored as a target for passive immunotherapy against complicated S. aureus infection. Staphylococcus aureus can express a large and diverse repertoire of virulence factors, including many different surface proteins, enzymes, and secreted toxins (1). Among the most potent of these virulence factors are the members of a family of secreted, heatstable proteins known as enterotoxins. More than 20 staphylococcal enterotoxins (SEs) have been discovered that demonstrate superantigenic (SAg) properties against T cells (2, 3). Superantigens can activate 20% to 50% of the T cell population by bypassing the traditional pathway of major histocompatibility complex (MHC)-dependent presentation of antigens to T cell receptors (TCRs). Instead, superantigens bind simultaneously to MHC class II (MHC-II) and TCRs, outside their antigen-binding groove, resulting in an excessive inflammatory response that can lead to toxic shock, multiorgan failure, and death. Superantigens are also associated with other immune-mediated diseases, including Kawasaki disease, atopic dermatitis, and chronic rhinosinusitis (4).The classical superantigens toxic shock syndrome toxin 1 (TSST-1), SEA, and SEB have been extensively studied due to their causative roles in toxic shock syndrome and food poisoning (5). However, advancements in sequencing methodologies have enabled the discovery of many more SEs whose roles in pathogenesis remain unknown (6). One of these toxins, SEl-K, has been shown to exhibit superantigenic properties, including V␤-specific T cell activation, pyrogenicity, emesis, and lethality in primates (7-9). Epidemiological studies have demonstrated the SEl-K-encoding genes to be among the most common SE genes in S. aureus clinical isolates (10-14). Additionally, SEl-K is the only SE gene to our knowledge that is si...

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Section: Discussionmentioning

confidence: 99%

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

et al. 2014

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“…In Europe, ST80-IV, ST8-IV, ST398-V and ST152-V were commonly reported [55]. In Mediterranean countries, the dominant clones are ST80-IV and ST5-IV/V [55,56].…”

Section: Community-associated Mrsa (Ca-mrsa)mentioning

confidence: 99%

“…In 2008, first case of MRSA isolated from hospitalized patient turned out to be a CA-MRSA which marked the arrival of CA-MRSA into nosocomial settings [57]. Since then, hospital outbreaks of S. aureus strains which are phenotypically and genotypically CA-MRSA, have been reported many parts of the world [55]. Entry of CA-MRSA into hospitals blurred the differences between CA-MRSA and HA-MRSA.…”

Section: Community-associated Mrsa (Ca-mrsa)mentioning

confidence: 99%

Staphylococcus aureus: Overview of Bacteriology, Clinical Diseases, Epidemiology, Antibiotic Resistance and Therapeutic Approach

Gnanamani¹,

Periasamy²,

Paul‐Satyaseela³

2017

Frontiers in Staphylococcus Aureus

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Staphylococcus aureus is an important human pathogen that causes wide range of infectious conditions both in nosocomial and community settings. The Gram-positive pathogen is armed with battery of virulence factors that facilitate to establish infections in the hosts. The organism is well known for its ability to acquire resistance to various antibiotic classes. The emergence and spread of methicillin-resistant S. aureus (MRSA) strains which are often multi-drug resistant in hospitals and subsequently in community resulted in significant mortality and morbidity. The epidemiology of MRSA has been evolving since its initial outbreak which necessitates a comprehensive medical approach to tackle this pathogen. Vancomycin has been the drug of choice for years but its utility was challenged by the emergence of resistance. In the last 10 years or so, newer anti-MRSA antibiotics were approved for clinical use. However, being notorious for developing antibiotic resistance, there is a continuous need for exploring novel anti-MRSA agents from various sources including plants and evaluation of non-antibiotic approaches.

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“…Although the clonal backgrounds of MSSAs are highly diverse, a number of dominant pandemic MSSA clones have been identified (8, 10, 11). Major MSSA lineages overlap the dominant circulating MRSA clones and include ST30, ST5, ST8, and, more recently, ST398 (12). ST398 was first described as both MSSA and MRSA among pig farmers in France (13, 14).…”

Section: Introductionmentioning

confidence: 99%

Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration

Uhlemann

McAdam

Sullivan

et al. 2017

mBio

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Methicillin-susceptible Staphylococcus aureus (MSSA) accounts for the majority of S. aureus infections globally, and yet surprisingly little is known about its clonal evolution. We applied comparative whole-genome sequencing (WGS) analyses to epidemiologically and geographically diverse ST398-MSSA, a pandemic lineage affecting both humans and livestock. Bayesian phylogenetic analysis predicted divergence of human-associated ST398-MSSA ~40 years ago. Isolates from Midwestern pigs and veterinarians differed substantially from those in New York City (NYC). Pig ST398 strains contained a large region of recombination representing imports from multiple sequence types (STs). Phylogeographic analyses supported the spread of ST398-MSSA along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. Applying pairwise single-nucleotide polymorphism (SNP) distances as a measure of genetic relatedness between isolates, we observed that ST398 not only clustered in households but also frequently extended across local social networks. Isolates collected from environmental surfaces reflected the full diversity of colonizing individuals, highlighting their potentially critical role as reservoirs for transmission and diversification. Strikingly, we observed high within-host SNP variability compared to our previous studies on the dominant methicillin-resistant Staphylococcus aureus (MRSA) clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300-MRSA and ST398-MSSA. Taken together, our study reveals local and international routes of transmission for a major MSSA clone, indicating key impacts of recombination and mutation on genetic diversification and highlighting important ecological differences from epidemic USA300. Our study demonstrates extensive local and international routes of transmission for a major MSSA clone despite the lack of substantial antibiotic resistance.

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Community-Associated Methicillin-Resistant Staphylococcus aureus Case Studies

Cited by 50 publications

References 186 publications

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

Staphylococcus aureus: Overview of Bacteriology, Clinical Diseases, Epidemiology, Antibiotic Resistance and Therapeutic Approach

Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration

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