Publications by authors named "Susan Boyle-Vavra"

56 Publications

Carriage of Methicillin-resistant in a Colony of Rhesus () and Cynomolgus () Macaques.

Comp Med 2019 08 2;69(4):311-320. Epub 2019 Aug 2.

Methicillin-resistant (MRSA) carriage and infection are well documented in the human and veterinary literature; however only limited information is available regarding MRSA carriage and infection in laboratory NHP populations. The objective of this study was to characterize MRSA carriage in a representative research colony of rhesus and cynomolgus macaques through a cross-sectional analysis of 300 animals. MRSA carriage was determined by using nasal culture. Demographic characteristics of carriers and noncarriers were compared to determine factors linked to increased risk of carriage, and MRSA isolates were analyzed to determine antimicrobial susceptibility patterns, staphylococcal chromosome cassette mec (SCCmec) type, and multilocus sequence type (ST). Culture results demonstrated MRSA carriage in 6.3% of the study population. Animals with greater numbers of veterinary or experimental interventions including antibiotic administration, steroid administration, dental procedures, and surgery were more likely to carry MRSA. Susceptibility results indicated that MRSA isolates were resistant to β-lactams, and all isolates were resistant to between 1 and 4 non β-lactam antibiotics. In addition, 73.7% of MRSA isolates were identified as ST188-SCCmec IV, an isolate previously observed in an unrelated population of macaques and 15.8% were ST3268-SCCmec V, which has only been described in macaques. A single isolate had a novel sequence type, ST3478, and carried SCCmec V. These results suggest that NHP-adapted strains of MRSA exist and highlight the emergence of antimicrobial resistance in laboratory NHP populations.
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http://dx.doi.org/10.30802/AALAS-CM-18-000089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733166PMC
August 2019

Identification of Small Molecules Exhibiting Oxacillin Synergy through a Novel Assay for Inhibition of Expression in Methicillin-Resistant Staphylococcus aureus.

Antimicrob Agents Chemother 2019 09 23;63(9). Epub 2019 Aug 23.

Center for Biomolecular Sciences and Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, USA

Methicillin-resistant (MRSA) strains that are resistant to all forms of penicillin have become an increasingly common and urgent problem threatening human health. They are responsible for a wide variety of infectious diseases ranging from minor skin abscesses to life-threatening severe infections. The operon that is conserved among strains encodes a three-component signal transduction system () that is responsible for sensing and responding to cell wall stress. We developed a novel and multifaceted assay to identify compounds that potentiate the activity of oxacillin, essentially restoring efficacy of oxacillin against MRSA, and performed high-throughput screening (HTS) to identify oxacillin potentiators. HTS of 13,840 small-molecule compounds from an antimicrobial-focused Life Chemicals library, using the MRSA cell-based assay, identified three different inhibitor scaffolds. Checkerboard assays for synergy with oxacillin, reverse transcriptase PCR (RT-PCR) assays against expression, and direct confirmation of interaction with VraS by surface plasmon resonance (SPR) further verified them to be viable hit compounds. A subsequent structure-activity relationship (SAR) study of the best scaffold with diverse analogs was utilized to improve potency and provides a strong foundation for further development.
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http://dx.doi.org/10.1128/AAC.02593-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709460PMC
September 2019

Vaccines targeting Staphylococcus aureus skin and bloodstream infections require different composition.

PLoS One 2019 10;14(6):e0217439. Epub 2019 Jun 10.

Department of Medicine, University of Maryland, Baltimore, MD, United States of America.

Staphylococcus aureus infections represent a major public health threat, but previous attempts at developing a universal vaccine have been unsuccessful. We attempted to identify a vaccine that would be protective against both skin/soft tissue and bloodstream infections. We first tested a panel of staphylococcal antigens that are conserved across strains, combined with aluminum hydroxide as an adjuvant, for their ability to induce protective immunity in both skin and bacteremia infection models. Antigens were identified that reduced dermonecrosis during skin infection, and other non-overlapping antigens were identified that showed trends to protection in the bacteremia model. However, individual antigens were not identified that mediated substantial protection in both the skin and bacteremia infection models. We therefore tested a variety of combinations of proteins to seek a single combination that could mediate protection in both models. After iterative testing, a vaccine consisting of 3 antigens, ABC transporter protein (SACOL2451), ABC2 transporter protein (SACOL0695), and α-hemolysin (SACOL1173), was identified as the most effective combination. This combination vaccine provided protection in a skin infection model. However, these antigens were only partially protective in the bacteremia infection model. Even by testing multiple different adjuvants, optimized efficacy in the skin infection model did not translate into efficacy in the bacteremia model. Thus protective vaccines against skin/soft tissue infections may not enable effective protection against bloodstream infections.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217439PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557488PMC
March 2020

Can Methicillin-resistant Staphylococcus aureus Silently Travel From the Gut to the Wound and Cause Postoperative Infection? Modeling the "Trojan Horse Hypothesis".

Ann Surg 2018 04;267(4):749-758

Center for Surgical Infection Research and Therapeutics, Pritzker School of Medicine, University of Chicago, Chicago, IL.

Objective: To determine whether intestinal colonization with methicillin-resistant Staphylococcus aureus (MRSA) can be the source of surgical site infections (SSIs).

Background: We hypothesized that gut-derived MRSA may cause SSIs via mechanisms in which circulating immune cells scavenge MRSA from the gut, home to surgical wounds, and cause infection (Trojan Horse Hypothesis).

Methods: MRSA gut colonization was achieved by disrupting the microbiota with antibiotics, imposing a period of starvation and introducing MRSA via gavage. Next, mice were subjected to a surgical injury (30% hepatectomy) and rectus muscle injury and ischemia before skin closure. All wounds were cultured before skin closure. To control for postoperative wound contamination, reiterative experiments were performed in mice in which the closed wound was painted with live MRSA for 2 consecutive postoperative days. To rule out extracellular bacteremia as a cause of wound infection, MRSA was injected intravenously in mice subjected to rectus muscle ischemia and injury.

Results: All wound cultures were negative before skin closure, ruling out intraoperative contamination. Out of 40 mice, 4 (10%) developed visible abscesses. Nine mice (22.5%) had MRSA positive cultures of the rectus muscle without visible abscesses. No SSIs were observed in mice injected intravenously with MRSA. Wounds painted with MRSA after closure did not develop infections. Circulating neutrophils from mice captured by flow cytometry demonstrated MRSA in their cytoplasm.

Conclusions: Immune cells as Trojan horses carrying gut-derived MRSA may be a plausible mechanism of SSIs in the absence of direct contamination.
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http://dx.doi.org/10.1097/SLA.0000000000002173DOI Listing
April 2018

Staphylococcal SCCmec elements encode an active MCM-like helicase and thus may be replicative.

Nat Struct Mol Biol 2016 Oct 29;23(10):891-898. Epub 2016 Aug 29.

Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.

Methicillin-resistant Staphylococcus aureus (MRSA) is a public-health threat worldwide. Although the mobile genomic island responsible for this phenotype, staphylococcal cassette chromosome (SCC), has been thought to be nonreplicative, we predicted DNA-replication-related functions for some of the conserved proteins encoded by SCC. We show that one of these, Cch, is homologous to the self-loading initiator helicases of an unrelated family of genomic islands, that it is an active 3'-to-5' helicase and that the adjacent ORF encodes a single-stranded DNA-binding protein. Our 2.9-Å crystal structure of intact Cch shows that it forms a hexameric ring. Cch, like the archaeal and eukaryotic MCM-family replicative helicases, belongs to the pre-sensor II insert clade of AAA+ ATPases. Additionally, we found that SCC elements are part of a broader family of mobile elements, all of which encode a replication initiator upstream of their recombinases. Replication after excision would enhance the efficiency of horizontal gene transfer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052118PMC
http://dx.doi.org/10.1038/nsmb.3286DOI Listing
October 2016

Impact of Staphylococcus aureus USA300 Colonization and Skin Infections on Systemic Immune Responses in Humans.

J Immunol 2016 08 11;197(4):1118-26. Epub 2016 Jul 11.

Department of Pediatrics, University of Chicago, Chicago, IL 60637; Department of Surgery, University of Chicago, Chicago, IL 60637.

Staphylococcus aureus is both a commensal and a pathogen, and USA300, a strain that is usually methicillin-resistant but can sometimes be methicillin-susceptible, has been causing skin and soft tissue infections (SSTIs) in epidemic proportions among otherwise healthy individuals. Although many people are colonized with S. aureus strains, including some with USA300, few of these colonized individuals develop SSTIs. This prompts the hypothesis that infections may develop in individuals with somewhat reduced innate and/or adaptive immune responses to S. aureus, either because prior S. aureus colonization has dampened such responses selectively, or because of more globally reduced immune reactivity. In this study, we analyzed the S. aureus colonization status and PBMC responses to innate and adaptive stimuli in 72 patients with SSTIs and 143 uninfected demographically matched controls. Contrary to the hypothesis formulated, PBMCs from infected patients obtained at the time of infection displayed enhanced innate cytokine production upon restimulation compared with PBMCs from controls, a difference that disappeared after infection resolution. Notably, PBMCs from patients infected with a documented USA300 SSTI displayed greater innate cytokine production than did those from patients infected with documented non-USA300 genotypes. Moreover, colonization with USA300 in infected patients, regardless of their infecting strain, correlated with increased production of IL-10, IL-17A, and IL-22 compared with patients colonized with non-USA300 subtypes. Thus, our results demonstrate that infected patients associated with USA300 either as an infecting strain, or as a colonizing strain, have systemic immune responses of greater magnitude than do those associated with other S. aureus subtypes.
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http://dx.doi.org/10.4049/jimmunol.1600549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976020PMC
August 2016

Intrahost Evolution of Methicillin-Resistant Staphylococcus aureus USA300 Among Individuals With Reoccurring Skin and Soft-Tissue Infections.

J Infect Dis 2016 09 10;214(6):895-905. Epub 2016 Jun 10.

Department of Pediatrics Department of Medicine, University of Chicago, Illinois.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is the leading cause of MRSA infections in the United States and has caused an epidemic of skin and soft-tissue infections. Recurrent infections with USA300 MRSA are common, yet intrahost evolution during persistence on an individual has not been studied. This gap hinders the ability to clinically manage recurrent infections and reconstruct transmission networks.

Methods: To characterize bacterial intrahost evolution, we examined the clinical courses of 4 subjects with 3-6 recurrent USA300 MRSA infections, using patient clinical data, including antibiotic exposure history, and whole-genome sequencing and phylogenetic analysis of all available MRSA isolates (n = 29).

Results: Among sequential isolates, we found variability in diversity, accumulation of mutations, and mobile genetic elements. Selection for antimicrobial-resistant populations was observed through both an increase in the number of plasmids conferring multidrug resistance and strain replacement by a resistant population. Two of 4 subjects had strain replacement with a genetically distinct USA300 MRSA population.

Discussions: During a 5-year period in 4 subjects, we identified development of antimicrobial resistance, intrahost evolution, and strain replacement among isolates from patients with recurrent MRSA infections. This calls into question the efficacy of decolonization to prevent recurrent infections and highlights the adaptive potential of USA300 and the need for effective sampling.
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http://dx.doi.org/10.1093/infdis/jiw242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996148PMC
September 2016

Proteomic Identification of saeRS-Dependent Targets Critical for Protective Humoral Immunity against Staphylococcus aureus Skin Infection.

Infect Immun 2015 Sep 13;83(9):3712-21. Epub 2015 Jul 13.

Department of Pediatrics, University of Chicago, Chicago, Illinois, USA

Recurrent Staphylococcus aureus skin and soft tissue infections (SSTIs) are common despite detectable antibody responses, leading to the belief that the immune response elicited by these infections is not protective. We recently reported that S. aureus USA300 SSTI elicits antibodies that protect against recurrent SSTI in BALB/c but not C57BL/6 mice, and in this study, we aimed to uncover the specificity of the protective antibodies. Using a proteomic approach, we found that S. aureus SSTI elicited broad polyclonal antibody responses in both BALB/c and C57BL/6 mice and identified 10 S. aureus antigens against which antibody levels were significantly higher in immune BALB/c serum. Four of the 10 antigens identified are regulated by the saeRS operon, suggesting a dominant role for saeRS in protection. Indeed, infection with USA300Δsae failed to protect against secondary SSTI with USA300, despite eliciting a strong polyclonal antibody response against antigens whose expression is not regulated by saeRS. Moreover, the antibody repertoire after infection with USA300Δsae lacked antibodies specific for 10 saeRS-regulated antigens, suggesting that all or a subset of these antigens are necessary to elicit protective immunity. Infection with USA300Δhla elicited modest protection against secondary SSTI, and complementation of USA300Δsae with hla restored protection but incompletely. Together, these findings support a role for both Hla and other saeRS-regulated antigens in eliciting protection and suggest that host differences in immune responses to saeRS-regulated antigens may determine whether S. aureus infection elicits protective or nonprotective immunity against recurrent infection.
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http://dx.doi.org/10.1128/IAI.00667-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534640PMC
September 2015

Pediatric Staphylococcus aureus Isolate Genotypes and Infections from the Dawn of the Community-Associated Methicillin-Resistant S. aureus Epidemic Era in Chicago, 1994 to 1997.

J Clin Microbiol 2015 Aug 27;53(8):2486-91. Epub 2015 May 27.

Department of Pediatrics, University of Chicago, Chicago, Illinois, USA.

Widespread infections with community-associated (CA) methicillin-resistant Staphylococcus 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-susceptible S. 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), and arcA and opp3, proxy markers for the arginine catabolic mobile element (ACME), characteristic of USA300 MRSA. MRSA isolates also underwent staphylococcal cassette chromosome mec (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 contained arcA or opp3. Only one MRSA isolate was USA300 by PFGE. This was a health care-associated (HA) MRSA isolate, negative for PVL, that carried SCCmec type II. USA300 with its characteristic features was not identified in the collection from the years 1994 to 1997.
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http://dx.doi.org/10.1128/JCM.00096-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508449PMC
August 2015

Staphylococcus aureus metabolic adaptations during the transition from a daptomycin susceptibility phenotype to a daptomycin nonsusceptibility phenotype.

Antimicrob Agents Chemother 2015 Jul 11;59(7):4226-38. Epub 2015 May 11.

School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA

Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. The success of S. aureus as a pathogen is due in part to its many virulence determinants and resistance to antimicrobials. In particular, methicillin-resistant S. aureus has emerged as a major cause of infections and led to increased use of the antibiotics vancomycin and daptomycin, which has increased the isolation of vancomycin-intermediate S. aureus and daptomycin-nonsusceptible S. aureus strains. The most common mechanism by which S. aureus acquires intermediate resistance to antibiotics is by adapting its physiology and metabolism to permit growth in the presence of these antibiotics, a process known as adaptive resistance. To better understand the physiological and metabolic changes associated with adaptive resistance, six daptomycin-susceptible and -nonsusceptible isogenic strain pairs were examined for changes in growth, competitive fitness, and metabolic alterations. Interestingly, daptomycin nonsusceptibility coincides with a slightly delayed transition to the postexponential growth phase and alterations in metabolism. Specifically, daptomycin-nonsusceptible strains have decreased tricarboxylic acid cycle activity, which correlates with increased synthesis of pyrimidines and purines and increased carbon flow to pathways associated with wall teichoic acid and peptidoglycan biosynthesis. Importantly, these data provided an opportunity to alter the daptomycin nonsusceptibility phenotype by manipulating bacterial metabolism, a first step in developing compounds that target metabolic pathways that can be used in combination with daptomycin to reduce treatment failures.
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http://dx.doi.org/10.1128/AAC.00160-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468685PMC
July 2015

USA300 and USA500 clonal lineages of Staphylococcus aureus do not produce a capsular polysaccharide due to conserved mutations in the cap5 locus.

mBio 2015 Apr 7;6(2). Epub 2015 Apr 7.

Department of Pediatrics, Section of Infectious Diseases, The University of Chicago, Chicago, Illinois, USA.

Unlabelled: The surface capsular polysaccharide (CP) is a virulence factor that has been used as an antigen in several successful vaccines against bacterial pathogens. A vaccine has not yet been licensed against Staphylococcus aureus, although two multicomponent vaccines that contain CP antigens are in clinical trials. In this study, we evaluated CP production in USA300 methicillin-resistant S. aureus (MRSA) isolates that have become the predominant community-associated MRSA clones in the United States. We found that all 167 USA300 MRSA and 50 USA300 methicillin-susceptible S. aureus (MSSA) isolates were CP negative (CP(-)). Moreover, all 16 USA500 isolates, which have been postulated to be the progenitor lineage of USA300, were also CP(-). Whole-genome sequence analysis of 146 CP(-) USA300 MRSA isolates revealed they all carry a cap5 locus with 4 conserved mutations compared with strain Newman. Genetic complementation experiments revealed that three of these mutations (in the cap5 promoter, cap5D nucleotide 994, and cap5E nucleotide 223) ablated CP production in USA300 and that Cap5E75 Asp, located in the coenzyme-binding domain, is essential for capsule production. All but three USA300 MSSA isolates had the same four cap5 mutations found in USA300 MRSA isolates. Most isolates with a USA500 pulsotype carried three of these four USA300-specific mutations, suggesting the fourth mutation occurred in the USA300 lineage. Phylogenetic analysis of the cap loci of our USA300 isolates as well as publicly available genomes from 41 other sequence types revealed that the USA300-specific cap5 mutations arose sequentially in S. aureus in a common ancestor of USA300 and USA500 isolates.

Importance: The USA300 MRSA clone emerged as a community-associated pathogen in the United States nearly 20 years ago. Since then, it has rapidly disseminated and now causes health care-associated infections. This study shows that the CP-negative (CP(-)) phenotype has persisted among USA300 isolates and is a universal and characteristic trait of this highly successful MRSA lineage. It is important to note that a vaccine consisting solely of CP antigens would not likely demonstrate high efficacy in the U.S. population, where about half of MRSA isolates comprise USA300. Moreover, conversion of a USA300 strain to a CP-positive (CP(+)) phenotype is unlikely in vivo or in vitro since it would require the reversion of 3 mutations. We have also established that USA300 MSSA isolates and USA500 isolates are CP(-) and provide new insight into the evolution of the USA300 and USA500 lineages.
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http://dx.doi.org/10.1128/mBio.02585-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453534PMC
April 2015

Transmission and microevolution of USA300 MRSA in U.S. households: evidence from whole-genome sequencing.

mBio 2015 Mar 10;6(2):e00054. Epub 2015 Mar 10.

Unlabelled: Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is a successful S. aureus clone in the United States and a common cause of skin and soft tissue infections (SSTIs). We performed whole-genome sequencing (WGS) of 146 USA300 MRSA isolates from SSTIs and colonization cultures obtained from an investigation conducted from 2008 to 2010 in Chicago and Los Angeles households that included an index case with an S. aureus SSTI. Identifying unique single nucleotide polymorphisms (SNPs) and analyzing whole-genome phylogeny, we characterized isolates to understand transmission dynamics, genetic relatedness, and microevolution of USA300 MRSA within the households. We also compared the 146 USA300 MRSA isolates from our study with the previously published genome sequences of the USA300 MRSA isolates from San Diego (n = 35) and New York City (n = 277). We found little genetic variation within the USA300 MRSA household isolates from Los Angeles (mean number of SNPs ± standard deviation, 17.6 ± 35; π nucleotide diversity, 3.1 × 10(-5)) or from Chicago (mean number of SNPs ± standard deviation, 12 ± 19; π nucleotide diversity, 3.1 × 10(-5)). The isolates within a household clustered into closely related monophyletic groups, suggesting the introduction into and transmission within each household of a single common USA300 ancestral strain. From a Bayesian evolutionary reconstruction, we inferred that USA300 persisted within households for 2.33 to 8.35 years prior to sampling. We also noted that fluoroquinolone-resistant USA300 clones emerged around 1995 and were more widespread in Los Angeles and New York City than in Chicago. Our findings strongly suggest that unique USA300 MRSA isolates are transmitted within households that contain an individual with an SSTI. Decolonization of household members may be a critical component of prevention programs to control USA300 MRSA spread in the United States.

Importance: USA300, a virulent and easily transmissible strain of methicillin-resistant Staphylococcus aureus (MRSA), is the predominant community-associated MRSA clone in the United States. It most commonly causes skin infections but also causes necrotizing pneumonia and endocarditis. Strategies to limit the spread of MRSA in the community can only be effective if we understand the most common sources of transmission and the microevolutionary processes that provide a fitness advantage to MRSA. We performed a whole-genome sequence comparison of 146 USA300 MRSA isolates from Chicago and Los Angeles. We show that households represent a frequent site of transmission and a long-term reservoir of USA300 strains; individuals within households transmit the same USA300 strain among themselves. Our study also reveals that a large proportion of the USA300 isolates sequenced are resistant to fluoroquinolone antibiotics. The significance of this study is that if households serve as long-term reservoirs of USA300, household MRSA eradication programs may result in a uniquely effective control method.
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http://dx.doi.org/10.1128/mBio.00054-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453535PMC
March 2015

High Staphylococcus aureus colonization prevalence among patients with skin and soft tissue infections and controls in an urban emergency department.

J Clin Microbiol 2015 Mar 24;53(3):810-5. Epub 2014 Dec 24.

University of Chicago, Section of Infectious Diseases, Department of Pediatrics, Chicago, Illinois, USA

Staphylococcus aureus is a commensal species that can also be a formidable pathogen. In the United States, an epidemic of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has been occurring for the last 15 years. In the context of a study in which we identified patients with skin and soft tissue infections (SSTIs) and randomized them to receive one of two antimicrobial treatment regimens, we assessed S. aureus colonization in the nares, throat, and perianal skin on the day of enrollment and 40 days after therapy. We compared the prevalence of colonization between the SSTI patients and an uninfected control population. A total of 144 subjects and 130 controls, predominantly African American, participated in this study, and 116 returned for a 40-day follow-up visit. Of the SSTI patients, 76% were colonized with S. aureus at enrollment, as were 65% of the controls. Patients were more likely than the controls to be colonized with USA300 MRSA (62/144 [43.1%] versus 11/130 [8.5%], respectively; P < 0.001). The nares were not the most common site of colonization. The colonization prevalence diminished somewhat after antibiotic treatment but remained high. The isolates that colonized the controls were more likely than those in the patients to be methicillin-susceptible S. aureus (MSSA) (74/84 [88.1%] versus 56/106 [52.8%], respectively; P < 0.001). In conclusion, the prevalence of S. aureus colonization among SSTI patients was high and often involved USA300 MRSA. The prevalence diminished somewhat with antimicrobial therapy but remained high at the 40-day follow-up visit. Control subjects were also colonized at a high prevalence but most often with a genetic background not associated with a clinical infection in this study. S. aureus is a commensal species and a pathogen. Plans for decolonization or eradication should take this distinction into account.
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http://dx.doi.org/10.1128/JCM.03221-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390638PMC
March 2015

Genomic and transcriptomic differences in community acquired methicillin resistant Staphylococcus aureus USA300 and USA400 strains.

BMC Genomics 2014 Dec 19;15:1145. Epub 2014 Dec 19.

Department of Pediatrics, Section of Critical Care, University of Chicago, Chicago, IL, 60637, USA.

Background: Staphylococcus aureus is a human pathogen responsible for substantial morbidity and mortality through its ability to cause a number of human infections including bacteremia, pneumonia and soft tissue infections. Of great concern is the emergence and dissemination of methicillin-resistant Staphylococcus aureus strains (MRSA) that are resistant to nearly all β-lactams. The emergence of the USA300 MRSA genetic background among community associated S. aureus infections (CA-MRSA) in the USA was followed by the disappearance of USA400 CA-MRSA isolates.

Results: To gain a greater understanding of the potential fitness advantages and virulence capacity of S. aureus USA300 clones, we performed whole genome sequencing of 15 USA300 and 4 USA400 clinical isolates. A comparison of representative genomes of the USA300 and USA400 pulsotypes indicates a number of differences in mobile genome elements. We examined the in vitro gene expression profiles by microarray hybridization and the in vivo transcriptomes during lung infection in mice of a USA300 and a USA400 MRSA strain by performing complete genome qRT-PCR analysis. The unique presence and increased expression of 6 exotoxins in USA300 (12- to 600-fold) compared to USA400 may contribute to the increased virulence of USA300 clones. Importantly, we also observed the up-regulation of prophage genes in USA300 (compared with USA400) during mouse lung infection (including genes encoded by both prophages ΦSa2usa and ΦSa3usa), suggesting that these prophages may play an important role in vivo by contributing to the elevated virulence characteristic of the USA300 clone.

Conclusions: We observed differences in the genetic content of USA300 and USA400 strains, as well as significant differences of in vitro and in vivo gene expression of mobile elements in a lung pneumonia model. This is the first study to document the global transcription differences between USA300 and USA400 strains during both in vitro and in vivo growth.
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http://dx.doi.org/10.1186/1471-2164-15-1145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630920PMC
December 2014

Staphylococcus aureus skin infection recurrences among household members: an examination of host, behavioral, and pathogen-level predictors.

Clin Infect Dis 2015 Mar 26;60(5):753-63. Epub 2014 Nov 26.

Section of Infectious Diseases, Department of Pediatrics, University of Chicago, Illinois.

Background: Many patients suffer from recurrent Staphylococcus aureus infections, but there are few data examining recurrence predictors.

Methods: We followed adults and children after treatment for S. aureus skin infections and their household contacts in Los Angeles and Chicago. We surveyed subjects for S. aureus body colonization, household fomite contamination, and behavioral and clinical factors at baseline and 3 and 6 months later. Using repeated measures modeling, we examined host, pathogen, behavioral, and clinical factors associated with recurrence.

Results: Among 330 index subjects, 182 (55%) were infected with an isolate of the USA300 methicillin-resistant S. aureus (MRSA) genetic background. Recurrences occurred in 39% by month 3 and 51% by month 6. Among 588 household contacts, 10% reported a skin infection by month 3 and 13% by month 6. Among index subjects, recurrence was associated with (P < .05) Los Angeles site, diabetes, recent hospitalization, recent skin infection, recent cephalexin use, and household S. aureus or MRSA fomite contamination; recurrence was inversely associated with recent contact sports participation. In the multivariate model, independent predictors of recurrence in index patients were recent hospitalization, household MRSA fomite contamination, and lack of recent contact sports participation. Among household contacts, independent predictors of subsequent skin infection were Chicago site, antibiotic use in the prior year, and skin infection in the prior 3 months.

Conclusions: In our longitudinal study, patients with a S. aureus skin infection were more likely to suffer a recurrence if household fomites were MRSA contaminated. Interventions to prevent recurrence may be enhanced by decontamination of household fomites.
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http://dx.doi.org/10.1093/cid/ciu943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402346PMC
March 2015

A randomized, controlled trial of chlorhexidine-soaked cloths to reduce methicillin-resistant and methicillin-susceptible Staphylococcus aureus carriage prevalence in an urban jail.

Infect Control Hosp Epidemiol 2014 Dec;35(12):1466-73

Department of Medicine, University of Chicago, Chicago, Illinois.

Objective: To assess an intervention to limit community-associated methicillin-resistant Staphylococcus aureus (MRSA) dissemination.

Design: Randomized, controlled trial.

Setting: County Jail, Dallas, Texas.

Participants: A total of 4,196 detainees in 68 detention tanks.

Methods: Tanks were randomly assigned to 1 of 3 groups: in group 1, detainees received cloths that contained chlorhexidine gluconate (CHG) to clean their entire skin surface 3 times per week for 6 months; group 2 received identical cloths containing only water; and group 3 received no skin treatment. During the study, all newly arrived detainees were invited to enroll. Nares and hand cultures were obtained at baseline and from all current enrollees at 2 and 6 months.

Results: At baseline, S. aureus was isolated from 41.2% and MRSA from 8.0% (nares and/or hand) of 947 enrollees. The average participation rate was 47%. At 6 months, MRSA carriage was 10.0% in group 3 and 8.7% in group 1 tanks (estimated absolute risk reduction [95% confidence interval (CI)], 1.4% [-4.8% to 7.1%]; P = .655). At 6 months, carriage of any S. aureus was 51.1% in group 3, 40.7% in group 1 (absolute risk reduction [95% CI], 10.4% [0.01%-20.1%]; P = .047), and 42.8% (absolute risk reduction [95% CI], 8.3% [-1.4% to 18.0%]; P = .099) in group 2.

Conclusions: Skin cleaning with CHG for 6 months in detainees, compared with no intervention, significantly decreased carriage of S. aureus, and use of water cloths produced a nonsignificant but similar decrease. A nonsignificant decrease in MRSA carriage was found with CHG cloth use.

Trial Registration: ClinicalTrials.gov identifier NCT00785200.
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http://dx.doi.org/10.1086/678606DOI Listing
December 2014

Persistent environmental contamination with USA300 methicillin-resistant Staphylococcus aureus and other pathogenic strain types in households with S. aureus skin infections.

Infect Control Hosp Epidemiol 2014 Nov 22;35(11):1373-82. Epub 2014 Sep 22.

Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.

Objective: To understand the genotypic spectrum of environmental contamination of Staphylococcus aureus in households and its persistence.

Design: Prospective longitudinal cohort investigation.

Setting: Index participants identified at 2 academic medical centers.

Participants: Adults and children with S. aureus skin infections and their household contacts in Los Angeles and Chicago.

Methods: Household fomites were surveyed for contamination at baseline and 3 months. All isolates underwent genetic typing.

Results: We enrolled 346 households, 88% of which completed the 3-month follow-up visit. S. aureus environmental contamination was 49% at baseline and 51% at 3 months. Among households with a USA300 methicillin-resistant S. aureus (MRSA) body infection isolate, environmental contamination with an indistinguishable MRSA strain was 58% at baseline and 63% at 3 months. Baseline factors associated with environmental contamination by the index subject's infection isolate were body colonization by any household member with the index subject's infection isolate at baseline (odds ratio [OR], 10.93 [95% confidence interval (CI), 5.75-20.79]), higher housing density (OR, 1.47 [95% CI, 1.10-1.96]), and more frequent household fomite cleaning (OR, 1.62 [95% CI, 1.16-2.27]). Household environmental contamination with the index subject's infection strain at 3 months was associated with USA300 MRSA and a synergistic interaction between baseline environmental contamination and body colonization by any household member with the index subject's infection strain.

Conclusions: We found that infecting S. aureus isolates frequently persisted environmentally in households 3 months after skin infection. Presence of pathogenic S. aureus strain type in the environment in a household may represent a persistent reservoir that places household members at risk of future infection.
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http://dx.doi.org/10.1086/678414DOI Listing
November 2014

Hand and nasal carriage of discordant Staphylococcus aureus isolates among urban jail detainees.

J Clin Microbiol 2014 Sep 23;52(9):3422-5. Epub 2014 Jun 23.

Department of Pediatrics, University of Chicago, Chicago, Illinois, USA.

In 928 Dallas County Jail detainees, nasal carriage of Staphylococcus aureus was found in 32.8% (26.5% methicillin-susceptible Staphylococcus aureus [MSSA] and 6.3% methicillin-resistant S. aureus [MRSA]), and hand carriage was found in 24.9% (20.7% MSSA and 4.1% MRSA). Among MRSA nasal carriers, 41% had hand MRSA carriage; 29% with hand MRSA carriage had no nasal S. aureus carriage. The prevalence of carriage was not associated with duration of the jail stay up to 180 days.
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http://dx.doi.org/10.1128/JCM.01190-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313174PMC
September 2014

Staphylococcus aureus bacteremia at 5 US academic medical centers, 2008-2011: significant geographic variation in community-onset infections.

Clin Infect Dis 2014 Sep 30;59(6):798-807. Epub 2014 May 30.

Department of David Geffen School of Medicine, University of California, Los Angeles (UCLA) Division of General Internal Medicine, Harbor-UCLA Medical Center and the Los Angeles Biomedical Research Institute, Torrance, California.

Background: The incidence of community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) bacteremia rose from the late 1990s through the 2000s. However, hospital-onset (HO) MRSA rates have recently declined in the United States and Europe.

Methods: Data were abstracted from infection prevention databases between 1 January 2008 and 31 December 2011 at 5 US academic medical centers to determine the number of single-patient blood cultures positive for MRSA and methicillin-susceptible S. aureus (MSSA) per calendar year, stratified into CO and HO infections.

Results: Across the 5 centers, 4171 episodes of bacteremia were identified. Center A (Los Angeles, California) experienced a significant decline in CO-MRSA bacteremia rates (from a peak in 2009 of 0.42 to 0.18 per 1000 patient-days in 2011 [P = .005]), whereas CO-MSSA rates remained stable. Centers B (San Francisco, California), D (Chicago, Illinois), and E (Raleigh-Durham, North Carolina) experienced a stable incidence of CO-MRSA and CO-MSSA bacteremia. In contrast, at center C (New York, New York), the incidence of CO-MRSA increased >3-fold (from 0.11 to 0.34 cases per 1000 patient-days [P < .001]). At most of the sites, HO-MRSA decreased and HO-MSSA rates were stable. USA300 accounted for 52% (104/202) of genotyped MRSA isolates overall, but this varied by center, ranging from 35% to 80%.

Conclusions: CO-MRSA rates and the contribution of USA300 MRSA varied dramatically across diverse geographical areas in the United States. Enhanced infection control efforts are unlikely to account for such variation in CO infection rates. Bioecological and clinical explanations for geographical differences in CO-MRSA bacteremia rates merit further study.
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http://dx.doi.org/10.1093/cid/ciu410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200044PMC
September 2014

Replacement of HA-MRSA by CA-MRSA infections at an academic medical center in the midwestern United States, 2004-5 to 2008.

PLoS One 2014 22;9(4):e92760. Epub 2014 Apr 22.

Department of Pediatrics, University of Chicago, Chicago, Illinois, United States of America.

We noted anecdotally that infections designated as health care-associated (HA-) MRSA by epidemiologic criteria seemed to be decreasing in incidence at the University of Chicago Medical Center (UCMC) after 2004. We compared MRSA patients seen at any site of clinical care at UCMC and the isolates that caused their infections in 2004-5 (n = 545) with those in 2008 (n = 135). The percent of patients with MRSA infections cultured > 2 days after hospital admission decreased from 19.5% in 2004-5 to 7.4% in 2008 (p = 0.001). The percent in 2004-5 compared with 2008 who had a hospitalization (49.1% to 26.7%, p = 0.001) or surgery (43.0% to 14.1%, p<0.001) in the previous year decreased. In 2008 a greater percent of patients was seen in the emergency department (23.1% vs. 39.3%) and a smaller percent both in intensive care units (15.6% vs. 6.7%) and in other inpatient units (40.7% vs. 32.6%) (p<0.001). The percent of patients with CA-MRSA infections by the CDC epidemiologic criteria increased from 36.5% in 2004-5 to 62.2% in 2008 (p<0.001). The percent of MRSA isolates sharing genetic characteristics of USA100 decreased from 27.9% (152/545) to 12.6% (17/135), while the percent with CA-MRSA (USA300) characteristics increased from 53.2% (290/545) to 66.7% (90/135). The percent of infections that were invasive did not change significantly. Our data suggest that HA-MRSA infections, both by epidemiologic and microbiologic criteria, relative to CA-MRSA, decreased between 2004-5 and 2008 at UCMC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092760PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995643PMC
January 2015

The role of the Staphylococcal VraTSR regulatory system on vancomycin resistance and vanA operon expression in vancomycin-resistant Staphylococcus aureus.

PLoS One 2014 15;9(1):e85873. Epub 2014 Jan 15.

Section of Infectious Diseases, Department of Pediatrics, University of Chicago, Chicago, Illinois, United States of America.

Vancomycin is often the preferred treatment for invasive methicillin-resistant Staphylococcus aureus (MRSA) infection. With the increase in incidence of MRSA infections, the use of vancomycin has increased and, as feared, isolates of vancomycin-resistant Staphylococcus aureus (VRSA) have emerged. VRSA isolates have acquired the entercoccal vanA operon contained on transposon (Tn) 1546 residing on a conjugal plasmid. VraTSR is a vancomycin and β-lactam-inducible three-component regulatory system encoded on the S. aureus chromosome that modulates the cell-wall stress response to cell-wall acting antibiotics. Mutation in vraTSR has shown to increase susceptibility to β-lactams and vancomycin in clinical VISA strains and in recombinant strain COLVA-200 which expresses a plasmid borne vanA operon. To date, the role of VraTSR in vanA operon expression in VRSA has not been demonstrated. In this study, the vraTSR operon was deleted from the first clinical VRSA strain (VRS1) by transduction with phage harvested from a USA300 vraTSR operon deletion strain. The absence of the vraTSR operon and presence of the vanA operon were confirmed in the transductant (VRS1Δvra) by PCR. Broth MIC determinations, demonstrated that the vancomycin MIC of VRS1Δvra (64 µg/ml) decreased by 16-fold compared with VRS1 (1024 µg/ml). The effect of the vraTSR operon deletion on expression of the van gene cluster (vanA, vanX and vanR) was examined by quantitative RT-PCR using relative quantification. A 2-5-fold decreased expression of the vanA operon genes occured in strain VRS1Δvra at stationary growth phase compared with the parent strain, VRS1. Both vancomycin resistance and vancomycin-induced expression of vanA and vanR were restored by complementation with a plasmid harboring the vraTSR operon. These findings demonstrate that expression in S. aureus of the horizontally acquired enterococcal vanA gene cluster is enhanced by the staphylococcal three-component cell wall stress regulatory system VraTSR, that is present in all S. aureus strains.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085873PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893269PMC
September 2014

Asymptomatic carriage of sequence type 398, spa type t571 methicillin-susceptible Staphylococcus aureus in an urban jail: a newly emerging, transmissible pathogenic strain.

J Clin Microbiol 2013 Jul 8;51(7):2443-7. Epub 2013 May 8.

Department of Pediatrics, University of Chicago, Chicago, Illinois, USA.

Sequence type 398 (ST398) Staphylococcus aureus, frequently carried by livestock, has caused severe human infections and often carries transmissible antibiotic resistance genes. Among methicillin-susceptible S. aureus isolates colonizing Dallas County Jail detainees, 13.2% were ST398, spa type t571, and were genetically similar to human colonization isolates from New York, Chicago, and the Dominican Republic.
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http://dx.doi.org/10.1128/JCM.01057-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697676PMC
July 2013

Roles of two large serine recombinases in mobilizing the methicillin-resistance cassette SCCmec.

Mol Microbiol 2013 Jun 23;88(6):1218-29. Epub 2013 May 23.

Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA.

Methicillin-resistant Staphylococcus aureus (MRSA) emerged via acquisition of a mobile element, staphylococcal cassette chromosome mec (SCCmec). Integration and excision of SCCmec is mediated by an unusual site-specific recombination system. Most variants of SCCmec encode two recombinases, CcrA and CcrB, that belong to the large serine family. Since CcrA and CcrB are always found together, we sought to address their specific roles. We show here that CcrA and CcrB can carry out both excisive and integrative recombination in Escherichia coli in the absence of any host-specific or SCCmec-encoded cofactors. CcrA and CcrB are promiscuous in their substrate choice: they act on many non-canonical pairs of recombination sites in addition to the canonical ones, which may explain tandem insertions into the SCCmec attachment site. Moreover, CcrB is always required, but CcrA is only required if one of the four half-sites is present. Recombinational activity correlates with DNA binding: CcrA recognizes only that half-site, which overlaps a conserved coding frame on the host chromosome. Therefore, we propose that CcrA serves as a specificity factor that emerged through modular evolution to enable recognition of a bacterial recombination site that is not an inverted repeat.
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http://dx.doi.org/10.1111/mmi.12253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714108PMC
June 2013

Comparing pulsed-field gel electrophoresis with multilocus sequence typing, spa typing, staphylococcal cassette chromosome mec (SCCmec) typing, and PCR for panton-valentine leukocidin, arcA, and opp3 in methicillin-resistant Staphylococcus aureus isolates at a U.S. Medical Center.

J Clin Microbiol 2013 Mar 26;51(3):814-9. Epub 2012 Dec 26.

Department of Medicine, University of Chicago, Chicago, Illinois, USA.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a common cause of skin infections and invasive infections in community dwellers in the United States since the late 1990s. Isolates characterized as USA300 by pulsed-field gel electrophoresis (PFGE) are the predominant strain type in these infections. USA100 and USA500 strains commonly cause health care-associated infections. We compared PFGE with a number of other methods of genotyping in a sample of 149 clinical MRSA isolates from the University of Chicago Medical Center. The 5 USA500 isolates yielded 3 spa types and 2 multilocus sequence types (MLSTs). Among the 24 USA100 isolates, 21 (88%) were of spa type t002, 19 (79%) were of ST5, 2 carried arcA and opp3, and 1 was Panton-Valentine leukocidin positive (PVL(+)). Among the 102 USA300 isolates, 96 (94%) were of ST8 and 94 (92%) were of spa type t008. The combination of traits that provided the best sensitivity (98%), specificity (97%), positive predictive value (PPV) (99%), and negative predictive value (NPV) (95%) for identifying USA300 isolates were the presence of the arcA gene and the presence of the PVL genes (area under the curve, 0.980; 95% confidence interval [CI], 0.955 to 1.0). PFGE did not delineate a homogeneous group of MRSA genetic backgrounds, as documented for other typing methods, particularly for USA500 and USA100 pulsotypes. Documenting the presence of arcA and PVL genes by PCR was an efficient and accurate means of identifying USA300 in a collection of MRSA isolates in which USA300 is common. None of the tested genotyping methods provided an accurate means of identifying the next most common PFGE-based backgrounds, USA100 and USA500.
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http://dx.doi.org/10.1128/JCM.02429-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592068PMC
March 2013

VraT/YvqF is required for methicillin resistance and activation of the VraSR regulon in Staphylococcus aureus.

Antimicrob Agents Chemother 2013 Jan 15;57(1):83-95. Epub 2012 Oct 15.

Department of Pediatrics, University of Chicago, Chicago, Illinois, USA.

Staphylococcus aureus infections caused by strains that are resistant to all forms of penicillin, so-called methicillin-resistant S. aureus (MRSA) strains, have become common. One strategy to counter MRSA infections is to use compounds that resensitize MRSA to methicillin. S. aureus responds to diverse classes of cell wall-inhibitory antibiotics, like methicillin, using the two-component regulatory system VraSR (vra) to up- or downregulate a set of genes (the cell wall stimulon) that presumably facilitates resistance to these antibiotics. Accordingly, VraS and VraR mutations decrease resistance to methicillin, vancomycin, and daptomycin cell wall antimicrobials. vraS and vraR are encoded together on a transcript downstream of two other genes, which we call vraU and vraT (previously called yvqF). By producing nonpolar deletions in vraU and vraT in a USA300 MRSA clinical isolate, we demonstrate that vraT is essential for optimal expression of methicillin resistance in vitro, whereas vraU is not required for this phenotype. The deletion of vraT also improved the outcomes of oxacillin therapy in mouse models of lung and skin infection. Since vraT expressed in trans did not complement a vra operon deletion, we conclude that VraT does not inactivate the antimicrobial. Genome-wide transcriptional microarray experiments reveal that VraT facilitates resistance by playing a necessary regulatory role in the VraSR-mediated cell wall stimulon. Our data prove that VraTSR comprise a novel three-component regulatory system required to facilitate resistance to cell wall agents in S. aureus. We also provide the first in vivo proof of principle for using VraT as a sole target to resensitize MRSA to β-lactams.
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http://dx.doi.org/10.1128/AAC.01651-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535960PMC
January 2013

CodY deletion enhances in vivo virulence of community-associated methicillin-resistant Staphylococcus aureus clone USA300.

Infect Immun 2012 Jul 23;80(7):2382-9. Epub 2012 Apr 23.

Section of Critical Care, University of Chicago, Chicago, Illinois, USA.

The Staphylococcus aureus global regulator CodY responds to nutrient availability by controlling the expression of target genes. In vitro, CodY represses the transcription of virulence genes, but it is not known if CodY also represses virulence in vivo. The dominant community-associated methicillin-resistant S. aureus (CA-MRSA) clone, USA300, is hypervirulent and has increased transcription of global regulators and virulence genes; these features are reminiscent of a strain defective in CodY. Sequence analysis revealed, however, that the codY genes of USA300 and other sequenced S. aureus isolates are not significantly different from the codY genes in strains known to have active CodY. codY was expressed in USA300, as well as in other pulsotypes assessed. Deletion of codY from a USA300 clinical isolate resulted in modestly increased expression of the global regulators agr and saeRS, as well as the gene encoding the toxin alpha-hemolysin (hla). A substantial increase (>30-fold) in expression of the lukF-PV gene, encoding part of the Panton-Valentine leukocidin (PVL), was observed in the codY mutant. All of these expression differences were reversed by complementation with a functional codY gene. Moreover, purified CodY protein bound upstream of the lukSF-PV operon, indicating that CodY directly represses expression of lukSF-PV. Deletion of codY increased the virulence of USA300 in necrotizing pneumonia and skin infection. Interestingly, deletion of lukSF-PV from the codY mutant did not attenuate virulence, indicating that the hypervirulence of the codY mutant was not explained by overexpression of PVL. These results demonstrate that CodY is active in USA300 and that CodY-mediated repression restrains the virulence of USA300.
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http://dx.doi.org/10.1128/IAI.06172-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416461PMC
July 2012

Staphylococcus aureus colonization among household contacts of patients with skin infections: risk factors, strain discordance, and complex ecology.

Clin Infect Dis 2012 Jun 3;54(11):1523-35. Epub 2012 Apr 3.

Division of Infectious Diseases, Harbor-UCLA Medical Center, and Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90509, USA.

Background: The USA300 methicillin resistant Staphylococcus aureus (MRSA) genetic background has rapidly emerged as the predominant cause of community-associated S. aureus infections in the U.S. However, epidemiologic characteristics of S. aureus household transmission are poorly understood.

Methods: We performed a cross-sectional study of adults and children with S. aureus skin infections and their household contacts in Los Angeles and Chicago. Subjects were surveyed for S. aureus colonization of the nares, oropharynx, and inguinal region and risk factors for S. aureus disease. All isolates underwent genetic typing.

Results: We enrolled 1162 persons (350 index patients and 812 household members). The most common infection isolate characteristic was ST8/SCCmec IV, PVL+ MRSA (USA300) (53%). S. aureus colonized 40% (137/350) of index patients and 50% (405/812) of household contacts. A nares-only survey would have missed 48% of S. aureus and 51% of MRSA colonized persons. Sixty-five percent of households had >1 S. aureus genetic background identified and 26% of MRSA isolates in household contacts were discordant with the index patients' infecting MRSA strain type. Factors independently associated (P < .05) with the index strain type colonizing household contacts were recent skin infection, recent cephalexin use, and USA300 genetic background.

Conclusions: In our study population, USA300 MRSA appeared more transmissible among household members compared with other S. aureus genetic backgrounds. Strain distribution was complex; >1 S. aureus genetic background was present in many households. S. aureus decolonization strategies may need to address extra-nasal colonization and the consequences of eradicating S. aureus genetic backgrounds infrequently associated with infection.
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http://dx.doi.org/10.1093/cid/cis213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348950PMC
June 2012

MRSA USA300 at Alaska Native Medical Center, Anchorage, Alaska, USA, 2000-2006.

Emerg Infect Dis 2012 Jan;18(1):105-8

Department of Medicine, University of Chicago, 5841 S Maryland Ave, MC6054, Chicago, IL 60637, USA.

To determine whether methicillin-resistant Staphylococcus aureus (MRSA) USA300 commonly caused infections among Alaska Natives, we examined clinical MRSA isolates from the Alaska Native Medical Center, Anchorage, during 2000-2006. Among Anchorage-region residents, USA300 was a minor constituent among MRSA isolates in 2000-2003 (11/68, 16%); by 2006, USA300 was the exclusive genotype identified (10/10).
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http://dx.doi.org/10.3201/eid1801.110746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310107PMC
January 2012

Methicillin-susceptible Staphylococcus aureus as a predominantly healthcare-associated pathogen: a possible reversal of roles?

PLoS One 2011 Apr 13;6(4):e18217. Epub 2011 Apr 13.

Department of Pediatrics, The University of Chicago, Chicago, Illinois, United States of America.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) strains have become common causes of skin and soft tissue infections (SSTI) among previously healthy people, a role of methicillin-susceptible (MSSA) isolates before the mid-1990s. We hypothesized that, as MRSA infections became more common among S. aureus infections in the community, perhaps MSSA infections had become more important as a cause of healthcare-associated infection.

Methods: We compared patients, including children and adults, with MRSA and MSSA infections at the University of Chicago Medical Center (UCMC) from all clinical units from July 1, 2004-June 30, 2005; we also compared the genotypes of the MRSA and MSSA infecting bacterial strains.

Results: Compared with MRSA patients, MSSA patients were more likely on bivariate analysis to have bacteremia, endocarditis, or sepsis (p = 0.03), to be an adult (p = 0.005), to be in the intensive care unit (21.9% vs. 15.6%) or another inpatient unit (45.6% vs. 40.7%) at the time of culture. MRSA (346/545) and MSSA (76/114) patients did not differ significantly in the proportion classified as HA-S. aureus by the CDC CA-MRSA definition (p = 0.5). The genetic backgrounds of MRSA and MSSA multilocus sequence type (ST) 1, ST5, ST8, ST30, and ST59 comprised in combination 94.5% of MRSA isolates and 50.9% of MSSA isolates. By logistic regression, being cared for in the Emergency Department (OR 4.6, CI 1.5-14.0, p = 0.008) was associated with MRSA infection.

Conclusion: Patients with MSSA at UCMC have characteristics consistent with a health-care-associated infection more often than do patients with MRSA; a possible role reversal has occurred for MSSA and MRSA strains. Clinical MSSA and MRSA strains shared genotype backgrounds.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0018217PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076382PMC
April 2011
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