scholarly journals Identification of a Highly Transmissible Animal-Independent Staphylococcus aureus ST398 Clone with Distinct Genomic and Cell Adhesion Properties

mBio ◽  
2012 ◽  
Vol 3 (2) ◽  
Author(s):  
Anne-Catrin Uhlemann ◽  
Stephen F. Porcella ◽  
Sheetal Trivedi ◽  
Sean B. Sullivan ◽  
Cory Hafer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Human Skin ◽  
Mobile Genetic Elements ◽  
Urban Setting ◽  
Adhesion Properties ◽  
Methicillin Resistant ◽  
Content Type ◽  
Genetic Elements ◽  
Skin Keratinocytes ◽  
Animal Contact

ABSTRACT A methicillin-resistant Staphylococcus aureus (MRSA) clone known as ST398 has emerged as a major cause of acute infections in individuals who have close contact with livestock. More recently, the emergence of an animal-independent ST398 methicillin-sensitive S. aureus (MSSA) clone has been documented in several countries. However, the limited surveillance of MSSA has precluded an accurate assessment of the global spread of ST398 and its clinical relevance. Here we provide evidence that ST398 is a frequent source of MSSA infections in northern Manhattan and is readily transmitted between individuals in households. This contrasts with the limited transmissibility of livestock-associated ST398 (LA-ST398) MRSA strains between humans. Our whole-genome sequence analysis revealed that the chromosome of the human-associated ST398 MSSA clone is smaller than that of the LA-ST398 MRSA reference strain S0385, due mainly to fewer mobile genetic elements (MGEs). In contrast, human ST398 MSSA isolates harbored the prophage φ3 and the human-specific immune evasion cluster (IEC) genes chp and scn. While most of the core genome was conserved between the human ST398 MSSA clone and S0385, these strains differed substantially in their repertoire and composition of intact adhesion genes. These genetic changes were associated with significantly enhanced adhesion of human ST398 MSSA isolates to human skin keratinocytes and keratin. We propose that the human ST398 MSSA clone can spread independent of animal contact using an optimized repertoire of MGEs and adhesion molecules adapted to transmission among humans. IMPORTANCE Staphylococcus aureus strains have generally been considered to be species specific. However, cross-species transfers of S. aureus clones, such as ST398 methicillin-resistant S. aureus (MRSA), from swine to humans have been reported. Recently, we observed the emergence of ST398 methicillin-susceptible S. aureus (MSSA) as a colonizing strain of humans in northern Manhattan. Here we report that ST398 is a frequent cause of MSSA infections in this urban setting. The ST398 MSSA clone was readily transmitted within households, independent of animal contact. We discovered that human ST398 MSSA genomes were smaller than that of the LA-ST398 strain S0385 due to fewer mobile genetic elements. Human and LA-ST398 strains also differed in their composition of adhesion genes and their ability to bind to human skin keratinocytes, providing a potential mechanism of S. aureus host adaptation. Our findings illustrate the importance of implementing molecular surveillance of MSSA given the evidence for the rapid and clinically undetected spread of ST398 MSSA.

scholarly journals Evolution of a 72-Kilobase Cointegrant, Conjugative Multiresistance Plasmid in Community-Associated Methicillin-Resistant Staphylococcus aureus Isolates from the Early 1990s

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Karina Yui Eto ◽  
Neville Firth ◽  
Amy M. Davis ◽  
Stephen M. Kwong ◽  
Marcelina Krysiak ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Resistance Genes ◽  
Tetracycline Resistance ◽  
Mobile Genetic Elements ◽  
Conjugative Plasmid ◽  
Penicillin Resistance ◽  
Virulence Determinants ◽  
Methicillin Resistant ◽  
Content Type ◽  
Genetic Elements

ABSTRACT Horizontal transfer of plasmids encoding antimicrobial resistance and virulence determinants has been instrumental in Staphylococcus aureus evolution, including the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA). In the early 1990s, the first CA-MRSA strain isolated in Western Australia (WA), WA-5, encoded cadmium, tetracycline, and penicillin resistance genes on plasmid pWBG753 (∼30 kb). WA-5 and pWBG753 appeared only briefly in WA; however, fusidic acid resistance plasmids related to pWBG753 were also present in the first European CA-MRSA isolates at the time. Here, we characterize a 72-kb conjugative plasmid, pWBG731, present in multiresistant WA-5-like clones from the same period. pWBG731 was a cointegrant formed from pWBG753 and a pWBG749 family conjugative plasmid. pWBG731 carried mupirocin, trimethoprim, cadmium, and penicillin resistance genes. The stepwise evolution of pWBG731 likely occurred through the combined actions of IS257, IS257-dependent miniature inverted-repeat transposable elements (MITEs), and the BinL resolution system of the β-lactamase transposon Tn552. An evolutionarily intermediate ∼42-kb nonconjugative plasmid, pWBG715, possessed the same resistance genes as pWBG731 but retained an integrated copy of the small tetracycline resistance plasmid pT181. IS257 likely facilitated the replacement of pT181 with conjugation genes on pWBG731, thus enabling autonomous transfer. Like conjugative plasmid pWBG749, pWBG731 also mobilized nonconjugative plasmids carrying oriT mimics. It seems likely that pWBG731 represents the product of multiple recombination events between the WA-5 pWBG753 plasmid and other mobile genetic elements present in indigenous community-associated methicillin-sensitive S. aureus (CA-MSSA) isolates. The molecular evolution of pWBG731 saliently illustrates how diverse mobile genetic elements can together facilitate rapid accrual and horizontal dissemination of multiresistance in S. aureus CA-MRSA.

scholarly journals Draft Genome Sequences of One Methicillin-Sensitive and Seven Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Isolates Obtained in California

2017 ◽  
Vol 5 (42) ◽  
Author(s):  
Samantha J. Hau ◽  
Darrell O. Bayles ◽  
David P. Alt ◽  
Tracy L. Nicholson
Keyword(s):  
Staphylococcus Aureus ◽  
Genome Sequence ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Draft Genome ◽  
Mobile Genetic Elements ◽  
Sequence Type ◽  
Commensal Bacterium ◽  
Genome Sequences ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACT Staphylococcus aureus is a commensal bacterium of humans that can cause a spectrum of diseases. An isolate’s capacity to cause disease is partially attributed to the acquisition of novel mobile genetic elements. This report provides the draft genome sequence of one methicillin-susceptible and seven methicillin-resistant clinical human S. aureus isolates.

scholarly journals Draft Genome Sequences of 14 Staphylococcus aureus Sequence Type 5 Isolates from California, USA

2017 ◽  
Vol 5 (13) ◽  
Author(s):  
Samantha J. Hau ◽  
Darrell O. Bayles ◽  
David P. Alt ◽  
Tracy L. Nicholson
Keyword(s):  
Staphylococcus Aureus ◽  
Draft Genome ◽  
Mobile Genetic Elements ◽  
Sequence Type ◽  
Genome Sequences ◽  
Content Type ◽  
Genetic Elements

ABSTRACT Staphylococcus aureus is part of the human epithelial microbiota; however, it is also a pathogen. The acquisition of mobile genetic elements plays a role in the virulence of S. aureus isolates and contributes to treatment failures. This report details the draft genome sequences of 14 clinical S. aureus isolates.

scholarly journals Complete Genome Sequences of Two Staphylococcus aureus Sequence Type 5 Isolates from California, USA

2017 ◽  
Vol 5 (13) ◽  
Author(s):  
Samantha J. Hau ◽  
Darrell O. Bayles ◽  
David P. Alt ◽  
Tracy L. Nicholson
Keyword(s):  
Staphylococcus Aureus ◽  
Complete Genome ◽  
Mobile Genetic Elements ◽  
Sequence Type ◽  
Human Diseases ◽  
Genome Sequences ◽  
Content Type ◽  
Genetic Elements

ABSTRACT Staphylococcus aureus causes a variety of human diseases ranging in severity. The pathogenicity of S. aureus can be partially attributed to the acquisition of mobile genetic elements. In this report, we provide two complete genome sequences from human clinical S. aureus isolates.

scholarly journals Efficacy of Skin and Nasal Povidone-Iodine Preparation against Mupirocin-Resistant Methicillin-Resistant Staphylococcus aureus and S. aureus within the Anterior Nares

2015 ◽  
Vol 59 (5) ◽  
pp. 2765-2773 ◽  
Author(s):  
Michele J. Anderson ◽  
Maren L. David ◽  
Matt Scholz ◽  
Sally J. Bull ◽  
Dan Morse ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Human Skin ◽  
Povidone Iodine ◽  
Human Subjects ◽  
Surgical Site Infections ◽  
Attractive Alternative ◽  
Methicillin Resistant ◽  
Content Type ◽  
Nasal Swabs ◽  
Mrsa Infection

ABSTRACTMupirocin decolonization of nasalStaphylococcus aureusprior to surgery decreases surgical-site infections; however, treatment requires 5 days, compliance is low, and resistance occurs. In 2010, 3M Company introduced povidone-iodine (PVP-I)-based skin and nasal antiseptic (Skin and Nasal Prep [SNP]). SNP has rapid, broad-spectrum antimicrobial activity. We tested SNP's efficacy using full-thickness tissue (porcine mucosal [PM] and human skin) explant models and human subjects. Prior to or following infection with methicillin-resistantStaphylococcus aureus(MRSA) (mupirocin sensitive and resistant), explants were treated with Betadine ophthalmic preparation (Bet), SNP, or mupirocin (Bactroban nasal ointment [BN]) or left untreated. One hour posttreatment, explants were washed with phosphate-buffered saline (PBS) plus 2% mucin. One, 6, or 12 h later, bacteria were recovered and enumerated. Alternatively, following baseline sampling, human subjects applied two consecutive applications of SNP or saline to their anterior nares. One, 6, and 12 h after application of the preparation (postprep), nasal swabs were obtained, andS. aureuswas enumerated. We observed that treatment of infected PM or human skin explants with SNP resulted in >2.0 log10CFU reduction in MRSA, regardless of mupirocin sensitivity, which was significantly different from the values for BN- and Bet-treated explants and untreated controls 1 h, 6 h, and 12 h after being washed with PBS plus mucin. Swabbing the anterior nares of human subjects with SNP significantly reduced residentS. aureuscompared to saline 1, 6, and 12 h postprep. Finally, pretreatment of PM explants with SNP, followed by a mucin rinse prior to infection, completely prevented MRSA infection. We conclude that SNP may be an attractive alternative for reducing the bioburden of anterior nares prior to surgery.

scholarly journals Methicillin-Resistant Staphylococcus aureus Sequence Type (ST) 5 Isolates from Health Care and Agricultural Sources Adhere Equivalently to Human Keratinocytes

2017 ◽  
Vol 84 (2) ◽  
Author(s):  
Samantha J. Hau ◽  
Steven Kellner ◽  
Kirsten C. Eberle ◽  
Ursula Waack ◽  
Susan L. Brockmeier ◽  
...  
Keyword(s):  
Public Health ◽  
Staphylococcus Aureus ◽  
Human Skin ◽  
Hospital Setting ◽  
Human Keratinocytes ◽  
The United States ◽  
Sequence Type ◽  
Methicillin Resistant ◽  
Content Type

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.

scholarly journals Mobile-Genetic-Element-Encoded Hypertolerance to Copper ProtectsStaphylococcus aureusfrom Killing by Host Phagocytes

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Marta Zapotoczna ◽  
Gustavo P. Riboldi ◽  
Ahmed M. Moustafa ◽  
Elizabeth Dickson ◽  
Apurva Narechania ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Human Blood ◽  
Immune Cells ◽  
Mobile Genetic Element ◽  
Mobile Genetic Elements ◽  
Clinical Isolates ◽  
Genetic Element ◽  
Methicillin Resistant ◽  
Content Type ◽  
Phagocytic Killing

ABSTRACTPathogens are exposed to toxic levels of copper during infection, and copper tolerance may be a general virulence mechanism used by bacteria to resist host defenses. In support of this, inactivation of copper exporter genes has been found to reduce the virulence of bacterial pathogensin vivo. Here we investigate the role of copper hypertolerance in methicillin-resistantStaphylococcus aureus(MRSA). We show that a copper hypertolerance operon (copB-mco), carried on a mobile genetic element (MGE), is prevalent in a collection of invasiveS. aureusstrains and more widely among clonal complex 22, 30, and 398 strains. ThecopBandmcogenes encode a copper efflux pump and a multicopper oxidase, respectively. Isogenic mutants lackingcopBormcohad impaired growth in subinhibitory concentrations of copper. Transfer of acopB-mco-carrying plasmid to a naive clinical isolate resulted in a gain of copper hypertolerance and enhanced bacterial survival inside primed macrophages. ThecopBandmcogenes were upregulated within infected macrophages, and their expression was dependent on the copper-sensitive operon repressor CsoR. IsogeniccopBandmcomutants were impaired in their ability to persist intracellularly in macrophages and were less resistant to phagocytic killing in human blood than the parent strain. The importance of copper-regulated genes in resistance to phagocytic killing was further elaborated using mutants expressing a copper-insensitive variant of CsoR. Our findings suggest that the gain of mobile genetic elements carrying copper hypertolerance genes contributes to the evolution of virulent strains ofS. aureusthat are better equipped to resist killing by host immune cells.IMPORTANCEMethicillin-resistantStaphylococcus aureus(MRSA) poses a substantial threat to human health worldwide and evolves rapidly by acquiring mobile genetic elements, such as plasmids. Here we investigate how thecopB-mcocopper hypertolerance operon carried on a mobile genetic element contributes to the virulence potential of clinical isolates of MRSA. Copper is a key component of innate immune bactericidal defenses. Here we show that copper hypertolerance genes enhance the survival ofS. aureusinside primed macrophages and in whole human blood. ThecopBandmcogenes are carried by clinical isolates responsible for invasive infections across Europe, and more broadly among three successful clonal lineages ofS. aureus. Our findings show that a gain of copper hypertolerance genes increases the resistance of MRSA to phagocytic killing by host immune cells and imply that acquisition of this mobile genetic element can contribute to the success of MRSA.

scholarly journals Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Jing Guan ◽  
Wanying Wang ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Mechanisms ◽  
Mobile Genetic Elements ◽  
Industrial Applications ◽  
Partial Deletion ◽  
Content Type ◽  
Genetic Elements ◽  
Type Iii ◽  
Wide Range ◽  
Novel Strategy

ABSTRACT Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCCmec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive trinucleotide pairings between a selected target and the 5′ tag of crRNA can block targeting. These findings add to our understanding of the molecular mechanisms of the type III-A CRISPR-Cas system and provide a novel strategy for the exploitation of engineered CRISPR immunity against integrated MGEs in bacteria for clinical and industrial applications. CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCCmec). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5′ tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCCmec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive trinucleotide pairings between a selected target and the 5′ tag of crRNA can block targeting. These findings add to our understanding of the molecular mechanisms of the type III-A CRISPR-Cas system and provide a novel strategy for the exploitation of engineered CRISPR immunity against integrated MGEs in bacteria for clinical and industrial applications.

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 ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Human Skin ◽  
Mobile Element ◽  
The United States ◽  
Aureus Strain ◽  
Major Public Health Problem ◽  
Methicillin Resistant ◽  
Content Type ◽  
Arginine Catabolic Mobile Element ◽  
Evolutionary Success

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.

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