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

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.

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Methicillin-Resistant Staphylococcus aureus Adaptation to Human Keratinocytes

mBio ◽

10.1128/mbio.00289-15 ◽

2015 ◽

Vol 6 (2) ◽

Cited By ~ 50

Author(s):

Grace Soong ◽

Franklin Paulino ◽

Sarah Wachtel ◽

Dane Parker ◽

Matthew Wickersham ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Human Skin ◽

Human Keratinocytes ◽

Staphylococcal Infection ◽

Inflammasome Activation ◽

Methicillin Resistant ◽

Content Type ◽

Caspase 1 ◽

Mrsa Infection ◽

Selection Of

ABSTRACT Skin is the most common site of Staphylococcus aureus infection. While most of these infections are self-limited, recurrent infections are common. Keratinocytes and recruited immune cells participate in skin defense against infection. We postulated that S. aureus is able to adapt to the milieu within human keratinocytes to avoid keratinocyte-mediated clearance. From a collection of S. aureus isolated from chronically infected patients with atopic dermatitis, we noted 22% had an agr mutant-like phenotype. Using several models of human skin infection, we demonstrate that toxin-deficient, agr mutants of methicillin-resistant S. aureus (MRSA) USA300 are able to persist within keratinocytes by stimulating autophagy and evading caspase-1 and inflammasome activation. MRSA infection induced keratinocyte autophagy, as evidenced by galectin-8 and LC3 accumulation. Autophagy promoted the degradation of inflammasome components and facilitated staphylococcal survival. The recovery of more than 58% agr or RNAIII mutants (P < 0.0001) of an inoculum of wild-type (WT) MRSA from within wortmannin-treated keratinocytes compared to control keratinocytes reflected the survival advantage for mutants no longer expressing agr-dependent toxins. Our results illustrate the dynamic interplay between S. aureus and keratinocytes that can result in the selection of mutants that have adapted specifically to evade keratinocyte-mediated clearance mechanisms. IMPORTANCE Human skin is a major site of staphylococcal infection, and keratinocytes actively participate in eradication of these pathogens. We demonstrate that methicillin-resistant Staphylococcus aureus (MRSA) is ingested by keratinocytes and activates caspase-1-mediated clearance through pyroptosis. Toxin-deficient MRSA mutants are selected within keratinocytes that fail to induce caspase-1 activity and keratinocyte-mediated clearance. These intracellular staphylococci induce autophagy that enhances their intracellular survival by diminishing inflammasome components. These findings suggest that S. aureus mutants, by exploiting autophagy, can persist within human keratinocytes.

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Daptomycin plus Fosfomycin, a Synergistic Combination in Experimental Implant-Associated Osteomyelitis Due to Methicillin-Resistant Staphylococcus aureus in Rats

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04246-14 ◽

2014 ◽

Vol 59 (2) ◽

pp. 859-863 ◽

Cited By ~ 9

Author(s):

Tilman Lingscheid ◽

Wolfgang Poeppl ◽

Dominik Bernitzky ◽

Luzia Veletzky ◽

Manuel Kussmann ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Once Daily ◽

Methicillin Resistant ◽

Bacterial Counts ◽

Content Type ◽

Bacterial Cultures ◽

Development Of Resistance ◽

Bacterial Inoculum ◽

Titanium Wire ◽

Mrsa Infection

ABSTRACTThe aim of this study was to evaluate the combination of daptomycin and fosfomycin in experimental chronic implant-associated osteomyelitis due to methicillin-resistantStaphylococcus aureus(MRSA). Infection was induced in the tibiae of rats by the insertion of a bacterial inoculum (1 to 5 × 108CFU/ml) of a clinical MRSA isolate and a titanium wire. Four weeks after infection, each animal was assigned to a treatment group: daptomycin monotherapy at 60 mg/kg of body weight once daily (n= 10), fosfomycin monotherapy at 40 mg/kg once daily (n= 10), or daptomycin and fosfomycin combined at 60 mg/kg and 40 mg/kg, respectively, once daily (n= 9). Ten animals were left untreated. After a 3-week treatment period, the animals were euthanized, and the infected tibiae and implants were processed for quantitative bacterial cultures. The bacterial cultures from bones were positive for MRSA in all animals in the untreated group, the daptomycin group, and the fosfomycin group, with median bacterial counts of 2.34 × 106CFU/g bone, 1.57 × 106CFU/g bone, and 3.48 × 102CFU/g bone, respectively. In the daptomycin-fosfomycin group, 6 out of 9 animals were positive for MRSA, with a median count of 7.92 CFU/g bone. Bacterial cultures derived from the titanium wires were negative in the fosfomycin- and daptomycin-fosfomycin-treated groups. Based on bacterial counts in bones, treatment with daptomycin-fosfomycin was statistically significantly superior to all that of the other groups (P≤ 0.003). Fosfomycin was superior to daptomycin and no treatment (P< 0.0001). No development of resistance was observed in any treatment arm. The combination of daptomycin and fosfomycin demonstrated synergism against MRSA in experimental implant-associated osteomyelitis.

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In VitroPharmacodynamics of Human Simulated Exposures of Ceftaroline and Daptomycin against MRSA, hVISA, and VISA with and without Prior Vancomycin Exposure

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01516-13 ◽

2013 ◽

Vol 58 (2) ◽

pp. 672-677 ◽

Cited By ~ 17

Author(s):

Amira A. Bhalodi ◽

Mao Hagihara ◽

David P. Nicolau ◽

Joseph L. Kuti

Keyword(s):

Staphylococcus Aureus ◽

Body Weight ◽

Sequential Therapy ◽

Free Drug ◽

Pharmacodynamic Model ◽

Prior Exposure ◽

Methicillin Resistant ◽

Content Type ◽

Mrsa Infection

ABSTRACTThe effects of prior vancomycin exposure on ceftaroline and daptomycin therapy against methicillin-resistantStaphylococcus aureus(MRSA) have not been widely studied. Humanized free-drug exposures of vancomycin at 1 g every 12 h (q12h), ceftaroline at 600 mg q12h, and daptomycin at 10 mg/kg of body weight q24h were simulated in a 96-hin vitropharmacodynamic model against three MRSA isolates, including one heteroresistant vancomycin-intermediateS. aureus(hVISA) isolate and one VISA isolate. A total of five regimens were tested: vancomycin, ceftaroline, and daptomycin alone for the entire 96 h, and then sequential therapy with vancomycin for 48 h followed by ceftaroline or daptomycin for 48 h. Microbiological responses were measured by the changes in log10CFU during 96 h from baseline. Control isolates grew to 9.16 ± 0.32, 9.13 ± 0.14, and 8.69 ± 0.28 log10CFU for MRSA, hVISA, and VISA, respectively. Vancomycin initially achieved ≥3 log10CFU reductions against the MRSA and hVISA isolates, followed by regrowth beginning at 48 h; minimal activity was observed against VISA. The change in 96-h log10CFU was largest for sequential therapy with vancomycin followed by ceftaroline (−5.22 ± 1.2,P= 0.010 versus ceftaroline) and for sequential therapy with vancomycin followed by ceftaroline (−3.60 ± 0.6,P= 0.037 versus daptomycin), compared with daptomycin (−2.24 ± 1.0), vancomycin (−1.40 ± 1.8), and sequential therapy with vancomycin followed by daptomycin (−1.32 ± 1.0,P> 0.5 for the last three regimens). Prior exposure of vancomycin at 1 g q12h reduced the initial microbiological response of daptomycin, particularly for hVISA and VISA isolates, but did not affect the response of ceftaroline. In the scenario of poor vancomycin response for high-inoculum MRSA infection, a ceftaroline-containing regimen may be preferred.

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Screening for Methicillin-Resistant Staphylococcus aureus Colonization Using Sponges

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2014.4 ◽

2015 ◽

Vol 36 (1) ◽

pp. 28-33 ◽

Cited By ~ 3

Author(s):

Chang-Seop Lee ◽

Bianca Montalmont ◽

Jessica A. O’Hara ◽

Alveena Syed ◽

Charma Chaussard ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Nasal Swab ◽

Methicillin Resistant Staphylococcus Aureus ◽

Type Ii ◽

Chain Reaction ◽

Methicillin Resistant ◽

Nasal Swabs ◽

Positive Specimen ◽

Mrsa Infection ◽

Polymerase Chain

OBJECTIVENasal swab culture is the standard method for identifying methicillin-resistant Staphylococcus aureus (MRSA) carriers. However, this method is known to miss a substantial portion of those carrying MRSA elsewhere. We hypothesized that the additional use of a sponge to collect skin culture samples would significantly improve the sensitivity of MRSA detection.DESIGNHospitalized patients with recent MRSA infection were enrolled and underwent MRSA screening of the forehead, nostrils, pharynx, axilla, and groin with separate swabs and the forehead, axilla, and groin with separate sponges. Staphylococcal cassette chromosome mec (SCCmec) typing was conducted by polymerase chain reaction (PCR).PATIENTSA total of 105 MRSA patients were included in the study.RESULTSAt least 1 specimen from 56.2% of the patients grew MRSA. Among patients with at least 1 positive specimen, the detection sensitivities were 79.7% for the swabs and 64.4% for the sponges. Notably, 86.4% were detected by a combination of sponges and nasal swab, and 72.9% were detected by a combination of pharyngeal and nasal swabs, whereas only 50.9% were detected by nasal swab alone (P<0.0001 and P=0.0003, respectively). Most isolates had SCCmec type II (59.9%) and IV (35.7%). No correlation was observed between the SCCmec types and collection sites.CONCLUSIONScreening using a sponge significantly improves MRSA detection when used in addition to screening with the standard nasal swab.Infect Control Hosp Epidemiol 2014;36(1): 28–33

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Nonredundant Roles of Interleukin-17A (IL-17A) and IL-22 in Murine Host Defense against Cutaneous and Hematogenous Infection Due to Methicillin-Resistant Staphylococcus aureus

Infection and Immunity ◽

10.1128/iai.01061-15 ◽

2015 ◽

Vol 83 (11) ◽

pp. 4427-4437 ◽

Cited By ~ 34

Author(s):

Liana C. Chan ◽

Siyang Chaili ◽

Scott G. Filler ◽

Kevin Barr ◽

Huiyuan Wang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

T Cell ◽

Host Defense ◽

Neutralizing Antibodies ◽

Neutrophil Infiltration ◽

Renal Tissue ◽

Methicillin Resistant ◽

Content Type ◽

Interleukin 17A ◽

Mrsa Infection

ABSTRACTStaphylococcus aureusis the leading cause of skin and skin structure infections (SSSI) in humans. Moreover, the high frequency of recurring SSSI due toS. aureus, particularly methicillin-resistantS. aureus(MRSA) strains, suggests that infection induces suboptimal anamnestic defenses. The present study addresses the hypothesis that interleukin-17A (IL-17A) and IL-22 play distinct roles in immunity to cutaneous and invasive MRSA infection in a mouse model of SSSI. Mice were treated with specific neutralizing antibodies against IL-17A and/or IL-22 and infected with MRSA, after which the severity of infection and host immune response were determined. Neutralization of either IL-17A or IL-22 reduced T cell and neutrophil infiltration and host defense peptide elaboration in lesions. These events corresponded with increased abscess severity, MRSA viability, and CFU density in skin. Interestingly, combined inhibition of IL-17A and IL-22 did not worsen abscesses but did increase gamma interferon (IFN-γ) expression at these sites. The inhibition of IL-22 led to a reduction in IL-17A expression, but not vice versa. These results suggest that the expression of IL-17A is at least partially dependent on IL-22 in this model. Inhibition of IL-17A but not IL-22 led to hematogenous dissemination to kidneys, which correlated with decreased T cell infiltration in renal tissue. Collectively, these findings indicate that IL-17A and IL-22 have complementary but nonredundant roles in host defense against cutaneous versus hematogenous infection. These insights may support targeted immune enhancement or other novel approaches to address the challenge of MRSA infection.

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Comparative Genomics of Vancomycin-Resistant Staphylococcus aureus Strains and Their Positions within the Clade Most Commonly Associated with Methicillin-Resistant S. aureus Hospital-Acquired Infection in the United States

mBio ◽

10.1128/mbio.00112-12 ◽

2012 ◽

Vol 3 (3) ◽

Cited By ~ 74

Author(s):

Veronica N. Kos ◽

Christopher A. Desjardins ◽

Allison Griggs ◽

Gustavo Cerqueira ◽

Andries Van Tonder ◽

...

Keyword(s):

United States ◽

Staphylococcus Aureus ◽

The United States ◽

Methicillin Resistant ◽

Content Type ◽

Mrsa Infection ◽

Vancomycin Resistant ◽

Foreign Dna ◽

Mrsa Strains ◽

Hospital Acquired

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistantS. aureus(VRSA) infection in the United States—all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift indprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition.IMPORTANCEInvasive methicillin-resistantStaphylococcus aureus(MRSA) infection now ranks among the leading causes of death in the United States. Vancomycin is a key last-line bactericidal drug for treating these infections. However, since 2002, vancomycin resistance has entered this species. Of the now 12 cases of vancomycin-resistantS. aureus(VRSA), each was believed to represent a new acquisition of the vancomycin-resistant transposon Tn1546from enterococcal donors. All acquisitions of Tn1546so far have occurred in MRSA strains of the clonal cluster 5 genetic background, the most common hospital lineage causing hospital-acquired MRSA infection. To understand the nature of these strains, we determined and examined the nucleotide sequences of the genomes of all available VRSA. Genome comparison identified candidate features that position strains of this lineage well for acquiring resistance to antibiotics in mixed infection.

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Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial

Journal of Clinical Microbiology ◽

10.1128/jcm.01444-16 ◽

2016 ◽

Vol 54 (11) ◽

pp. 2735-2742 ◽

Cited By ~ 45

Author(s):

Mary K. Hayden ◽

Karen Lolans ◽

Katherine Haffenreffer ◽

Taliser R. Avery ◽

Ken Kleinman ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Cluster Randomized Trial ◽

Confidence Limits ◽

Methicillin Resistant ◽

Content Type ◽

Mrsa Infection ◽

Mupirocin Resistance ◽

Cluster Randomized ◽

High Level

Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 μg/ml), and 5/814 (0.6%) carried qacA or qacB . At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution.

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Innate Immune Memory Contributes to Host Defense against Recurrent Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus

Infection and Immunity ◽

10.1128/iai.00876-16 ◽

2016 ◽

Vol 85 (2) ◽

Cited By ~ 15

Author(s):

Liana C. Chan ◽

Siyang Chaili ◽

Scott G. Filler ◽

Lloyd S. Miller ◽

Norma V. Solis ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Host Defense ◽

Protective Efficacy ◽

Innate Immune ◽

Immune Memory ◽

Wild Type ◽

Methicillin Resistant ◽

Content Type ◽

Skin Structure ◽

Mrsa Infection

ABSTRACT Staphylococcus aureus is the leading cause of skin and skin structure infections (SSSI). The high frequency of recurring SSSI due to S. aureus, including methicillin-resistant S. aureus (MRSA) strains, despite high titers of specific antibodies and circulating T cells, implies that traditional adaptive immunity imparts incomplete protection. We hypothesized that innate immune memory contributes to the protective host defense against recurring MRSA infection. To test this hypothesis, SSSI was induced in wild-type and rag1 −/− mice in the BALB/c and C57BL/6 backgrounds. Prior infection (priming) of wild-type and rag1 −/− mice of either background afforded protection against repeat infection, as evidenced by reduced abscess severities and decreased CFU densities compared to those in naive controls. Interestingly, protection was greater on the previously infected flank than on the naive flank for wild-type and rag1 −/− mice. For wild-type mice, protective efficacy corresponded to increased infiltration of neutrophils (polymorphonuclear leukocytes [PMN]), macrophages (MΦ), Langerin+ dendritic cells (LDC), and natural killer (NK) cells. Protection was associated with the induction of interleukin-17A (IL-17A), IL-22, and gamma interferon (IFN-γ) as well as the antimicrobial peptides CRAMP and mβD-3. Priming also protected rag1 −/− mice against recurring SSSI, with increased MΦ and LDC infiltration and induction of IL-22, CRAMP, and mβD-3. These findings suggest that innate immune memory, mediated by specific cellular and molecular programs, likely contributes to the localized host defense in recurrent MRSA SSSI. These insights support the development of targeted immunotherapeutic strategies to address the challenge of MRSA infection.

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Commercially Distributed Meat as a Potential Vehicle for Community-Acquired Methicillin-Resistant Staphylococcus aureus

Applied and Environmental Microbiology ◽

10.1128/aem.07470-11 ◽

2012 ◽

Vol 78 (8) ◽

pp. 2797-2802 ◽

Cited By ~ 33

Author(s):

Kikuyo Ogata ◽

Hiroshi Narimatsu ◽

Masahiro Suzuki ◽

Wataru Higuchi ◽

Tatsuo Yamamoto ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Drug Susceptibility ◽

Methicillin Resistant ◽

Content Type ◽

Reading Frame ◽

Type Iv ◽

Mrsa Infection ◽

Stool Samples ◽

Mrsa Strains ◽

Meat Samples

ABSTRACTThe incidence of community-acquired methicillin-resistantStaphylococcus aureus(CA-MRSA) infection has been increasing; however, the sources of infection remain unclear. Therefore, we investigated the involvement of meat as a possible mediator of CA-MRSA infection. We examined the distribution of MRSA strains in commercially distributed raw meat samples (n= 197) and diarrheal stool samples of outpatients (n= 1,287) that were collected in Oita Prefecture, Japan, between 2003 and 2009 for routine legal inspections. Fourteen MRSA strains were isolated from three meat and 11 stool samples. Among these, seven isolates from three meat and four stool samples exhibited the same epidemiological marker profiles [coagulase type III, staphylococcal enterotoxin C, staphylococcal chromosomal cassettemec(SCCmec) type IV, ST8,spatype 606 (t1767), and toxic shock syndrome toxin-1 (TSST-1) producing type]. Furthermore, of the seven strains, three isolates from two meat samples and one stool sample collected in 2007 exhibited completely identical characteristics with respect to phage open reading frame (ORF) typing, pulsed-field gel electrophoresis, and drug susceptibility profiles. The results suggest that commercially distributed meat could play a role in the prevalence of CA-MRSA in the community.

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

mBio ◽

10.1128/mbio.00027-12 ◽

2012 ◽

Vol 3 (2) ◽

Cited By ~ 118

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.

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