A New Local Variant (ST764) of the Globally Disseminated ST5 Lineage of Hospital-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) Carrying the Virulence Determinants of Community-Associated MRSA

ABSTRACTThe ST5 lineage of methicillin-resistantStaphylococcus aureus(MRSA) is one of the most globally disseminated hospital-associated MRSA (HA-MRSA) lineages. We isolated a new local variant (designated ST764) over at least 5 years that causes invasive infections, including necrotizing fasciitis, and is carried by medical students, as well as household members. Analysis of the genome sequence of one isolate compared to that of the reference ST5 strain revealed that ST764 had acquired virulence traits similar to those of community-associated MRSA (CA-MRSA) through the acquisition of two new mobile genetic elements, ACMEII and SaPInn54, which carried ACMEarcAand the staphylococcal enterotoxin B gene (seb), respectively, and through enhanced expression of cytolytic peptide genes, although ST764 was negative for Panton-Valentine leukocidin. Other differences between ST764 and ST5 included the acquisition of an ACMEII-related cassette (cJR1), prophage φ2NN54, and streptococcal Tn5251and decreased numbers of copies of Tn554. As for superantigen genes, although the two possessedseg,sei,sem,sen, andseo, ST764 lackedtst,sec,sel, andsep. The data suggest that ST764 MRSA is a novel hybrid variant of ST5 HA-MRSA with the characteristics of CA-MRSA and that the evolution of ST764 includes multiple steps, e.g., acquisition of novel or nonstaphylococcal mobile elements.

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Empyema thoracis secondary to community-acquired Panton-Valentine leukocidin (PVL) methicillin-resistant Staphylococcus aureus (MRSA) infection

BMJ Case Reports ◽

10.1136/bcr-2018-228297 ◽

2019 ◽

Vol 12 (4) ◽

pp. e228297 ◽

Cited By ~ 1

Author(s):

Shahbaz Piracha ◽

Syeda Saba Muneer Ahmed ◽

Samira Mohd Afzal ◽

Muhammad Badar Ganaie

Keyword(s):

Staphylococcus Aureus ◽

Outpatient Setting ◽

Empyema Thoracis ◽

Methicillin Resistant ◽

Public Health Challenges ◽

Invasive Infections ◽

Mrsa Infection ◽

The Uk ◽

Panton Valentine Leukocidin ◽

Valentine Leukocidin

We report a case of a previously fit middle-aged man presenting to the outpatient setting with unilateral pleural effusion, with minimal symptoms. On subsequent investigations, he was diagnosed with empyema thoracis secondary to Panton-Valentine leukocidin (PVL)-toxin positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA). The patient was treated with prolonged antibiotics and pleural drainage, and he remained haemodynamically stable throughout hospital admission. PVL is a cytolytic exotoxin produced by some strains of S. aureus. Such strains often cause recurrent skin and soft tissue infections, usually in previously fit and healthy individuals. Less commonly, invasive infections occur; these carry a high mortality rate if associated with necrotising pneumonia or septic shock. PVL genes are present in approximately 2% of clinical isolates of S. aureus in the UK. PVL-producing MRSA infections are on the rise and present significant clinical and public health challenges.

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Ceftobiprole EfficacyIn Vitroagainst Panton-Valentine Leukocidin Production andIn Vivoagainst Community-Associated Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rabbits

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00926-12 ◽

2012 ◽

Vol 56 (12) ◽

pp. 6291-6297 ◽

Cited By ~ 9

Author(s):

Azzam Saleh-Mghir ◽

Oana Dumitrescu ◽

Aurélien Dinh ◽

Yassine Boutrad ◽

Laurent Massias ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant ◽

Content Type ◽

The Mean ◽

Mrsa Strains ◽

Time Kill ◽

Panton Valentine Leukocidin ◽

Valentine Leukocidin

ABSTRACTCommunity-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) can cause osteomyelitis with severe sepsis and/or local complications in which a Panton-Valentine leukocidin (PVL) role is suspected.In vitrosub-MIC antibiotic effects on growth and PVL production by 11 PVL+MRSA strains, including the major CA-MRSA clones (USA300, including the LAC strain; USA400; and USA1000), and 11 PVL+methicillin-susceptibleS. aureus(MSSA) strains were tested in microplate culture. Time-kill analyses with ceftobiprole at its MIC were also run with LAC. Efficacies of ceftobiprole (40 mg/kg of body weight subcutaneously [s.c.] four times a day [q.i.d.]) or vancomycin (60 mg/kg intramuscularly [i.m.] twice a day [b.i.d.]) alone or combined with rifampin (10 mg/kg b.i.d.) against rabbit CA-MRSA osteomyelitis, induced by tibial injection of 3.4 × 107CFU of LAC, were compared. Treatment, started 14 days postinoculation, lasted 14 days.In vitro, 6/11 strains cultured with sub-MICs of ceftobiprole produced 1.6- to 4.8-fold more PVL than did the controls, with no link to specific clones. Rifampin decreased PVL production by all tested strains. In time-kill analyses at the LAC MIC (0.75 mg/liter), PVL production rose transiently at 6 and 8 h and then declined 2-fold at 16 h, concomitant with a 2-log10-CFU-count decrease.In vivo, the mean log10CFU/g of bone for ceftobiprole (1.44 ± 0.40) was significantly lower than that for vancomycin (2.37 ± 1.22) (P= 0.034), with 7/10 versus 5/11 bones sterilized, respectively. Combination with rifampin enhanced ceftobiprole (1.16 ± 0.04 CFU/g of bone [P= 0.056], 11/11 sterile bones) and vancomycin (1.23 ± 0.06 CFU/g [P= 0.011], 11/11 sterile bones) efficacies. Ceftobiprole bactericidal activity and the rifampin anti-PVL effect could play a role in these findings, which should be of interest for treating CA-MRSA osteomyelitis.

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Panton-Valentine Leukocidin-Positive Methicillin-Resistant Staphylococcus Aureus with Reduced Vancomycin Susceptibility: An Emerging Trend?

Medical University ◽

10.2478/medu-2020-0020 ◽

2020 ◽

Vol 3 (4) ◽

pp. 165-181

Author(s):

Tatsuo Yamamoto ◽

Olga E. Khokhlova ◽

Tsai-Wen Wan ◽

Darya N. Akhusheva ◽

Ivan V Reva ◽

...

Keyword(s):

Staphylococcus Aureus ◽

The United States ◽

Multidrug Resistant ◽

Virus Infections ◽

Methicillin Resistant ◽

Invasive Infections ◽

Spread Factor ◽

Healthcare Associated ◽

Panton Valentine Leukocidin ◽

Valentine Leukocidin

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug-resistant nosocomial pathogen. This class of MRSA, first reported in the early 1960s and now termed healthcare-associated MRSA (HA-MRSA), was followed by a newer class of MRSA, community-associated MRSA (CA-MRSA). The unique feature of the initial CAMRSA included Panton-Valentine leukocidin (PVL), an abscess-associated toxin and also S. aureus spread factor. CA-MRSA usually causes skin and soft-tissue infections, but occasionally causes invasive infections, including (necrotizing) pneumonia, sometimes preceded by respiratory virus infections. The most successful CA-MRSA USA300 (ST8/SCCmecIVa) caused an epidemic in the United States. In Russia, we first detected PVL-positive CAMRSA (ST30/SCCmecIVc) in Vladivostok in 2006, but with no more PVL-positive MRSA isolation. However, we recently isolated four lineages of PVL-positive MRSA in Krasnoyarsk. Regarding chemotherapy against invasive MRSA infections, vancomycin still remains a gold standard, in addition to some other anti-MRSA agents such as teicoplanin, linezolid, and daptomycin. For resistance, vancomycin-resistant MRSA (VRSA) with MICs of ≥16 μg/mL appeared in patients, but cases are still limited. However, clinically, infections from strains with MICs of ≥1.5 μg/mL, even albeit with susceptible MICs (≤2 μg/mL), respond poorly to vancomycin. Some of those bacteria have been bacteriologically characterized as vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA), generally with HA-MRSA genetic backgrounds. The features of the above PVL-positive Krasnoyarsk MRSA include reduced susceptibility to vancomycin, which meets the criteria of hVISA. In this review, we discuss a possible new trend of PVL-positive hVISA, which may spread and threaten human health in community settings.

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agrDysfunction Affects Staphylococcal Cassette ChromosomemecType-Dependent Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Bacteremia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04962-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3125-3132 ◽

Cited By ~ 15

Author(s):

Chang Kyung Kang ◽

Jeong Eun Cho ◽

Yoon Jeong Choi ◽

Younghee Jung ◽

Nak-Hyun Kim ◽

...

Keyword(s):

Staphylococcus Aureus ◽

South Korea ◽

Clinical Outcomes ◽

Tertiary Care ◽

High Rate ◽

Care Hospital ◽

Virulence Determinants ◽

Methicillin Resistant ◽

Content Type ◽

Type Iv

ABSTRACTStaphylococcal cassette chromosomemecelement (SCCmec) type-dependent clinical outcomes may vary due to geographical variation in the presence of virulence determinants. We compared the microbiological factors and mortality attributed to methicillin-resistantStaphylococcus aureus(MRSA) bacteremia between SCCmectypes II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care hospital (South Korea) over a 4.5-year period were reviewed. We studied the microbiological factors associated with all blood MRSA isolates, includingspatype,agrtype,agrdysfunction, and the genes for Panton-Valentine leukocidin (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCCmectype. Of 195 cases, 137 involved SCCmectypes II/III, and 58 involved type IV. The mortality attributed to MRSA bacteremia was less frequent among the SCCmectype IV (5/58) than that among types II/III (39/137,P= 0.002). This difference remained significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.04 to 0.49;P= 0.002). Of the microbiological factors tested,agrdysfunction was the only significant factor that showed different positivity between the SCCmectypes, and it was independently associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to 12.92;P= 0.003). SCCmectype IV is associated with lower MRSA bacteremia-attributed mortality than are types II/III, which might be explained by the high rate ofagrdysfunction in SCCmectypes II/III in South Korea.

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In VivoEfficacy of Ceftaroline Fosamil in a Methicillin-Resistant Panton-Valentine Leukocidin-Producing Staphylococcus aureus Rabbit Pneumonia Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01707-13 ◽

2014 ◽

Vol 58 (4) ◽

pp. 1855-1861 ◽

Cited By ~ 11

Author(s):

Delphine Croisier-Bertin ◽

Davy Hayez ◽

Sonia Da Silva ◽

Delphine Labrousse ◽

Donald Biek ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Enzyme Linked Immunosorbent Assay ◽

Pulmonary Tissue ◽

Ceftaroline Fosamil ◽

Methicillin Resistant ◽

Content Type ◽

Panton Valentine Leukocidin ◽

Valentine Leukocidin

ABSTRACTCeftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with broad-spectrumin vitroactivity against Gram-positive organisms, including methicillin-resistantStaphylococcus aureus(MRSA) and multidrug-resistantStreptococcus pneumoniae(MDRSP), and common Gram-negative pathogens. This study investigated thein vivoactivity of ceftaroline fosamil compared with clindamycin, linezolid, and vancomycin in a severe pneumonia model due to MRSA-producing Panton-Valentine leukocidin (PVL). A USA300 PVL-positive clone was used to induce pneumonia in rabbits. Infected rabbits were randomly assigned to no treatment or simulated human-equivalent dosing with ceftaroline fosamil, clindamycin, linezolid, or vancomycin. Residual bacterial concentrations in the lungs and spleen were assessed after 48 h of treatment. PVL expression was measured using a specific enzyme-linked immunosorbent assay (ELISA). Ceftaroline, clindamycin, and linezolid considerably reduced mortality rates compared with the control, whereas vancomycin did not. Pulmonary and splenic bacterial titers and PVL concentrations were greatly reduced by ceftaroline, clindamycin, and linezolid. Ceftaroline, clindamycin, and linezolid were associated with reduced pulmonary tissue damage based on significantly lower macroscopic scores. Ceftaroline fosamil, clindamycin, and, to a lesser extent, linezolid were efficient in reducing bacterial titers in both the lungs and spleen and decreasing macroscopic scores and PVL production compared with the control.

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Evolution and Population Dynamics of Clonal Complex 152 Community-Associated Methicillin-Resistant Staphylococcus aureus

mSphere ◽

10.1128/msphere.00226-20 ◽

2020 ◽

Vol 5 (4) ◽

Author(s):

Sharmin Baig ◽

Anders Rhod Larsen ◽

Patrícia Martins Simões ◽

Frédéric Laurent ◽

Thor Bech Johannesen ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Clonal Complex ◽

Whole Genome ◽

Methicillin Resistant ◽

Content Type ◽

Type V ◽

Panton Valentine Leukocidin ◽

Valentine Leukocidin

ABSTRACT Since the late 1990s, changes in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) were recognized with the emergence of community-associated MRSA (CA-MRSA). CA-MRSA belonging to clonal complex 152 (CC152), carrying the small staphylococcal cassette chromosome mec (SCCmec) type V and encoding the Panton-Valentine leukocidin (PVL), has been observed in Europe. The aim of this study was to investigate its origin, evolution, and dissemination. Whole-genome sequencing was performed on a global collection of 149 CC152 isolates spanning 20 years (93 methicillin-susceptible S. aureus [MSSA] and 56 MRSA isolates). Core genome phylogeny, Bayesian inference, in silico resistance analyses, and genomic characterization were applied. Phylogenetic analysis revealed two major distinct clades, one dominated by MSSA and the other populated only by MRSA. The MSSA isolates were predominately from sub-Saharan Africa, whereas MRSA was almost exclusively from Europe. The European MRSA isolates all harbored an SCCmec type V (5C2&5) element, whereas other SCCmec elements were sporadically detected in MRSA from the otherwise MSSA-dominated clade, including SCCmec types IV (2B), V (5C2), and XIII (9A). In total, 93% of the studied CC152 isolates were PVL positive. Bayesian coalescent inference suggests an emergence of the European CC152-MRSA in the 1990s, while the CC152 lineage dates back to the 1970s. The CA-MRSA CC152 clone mimics the European CC80 CA-MRSA lineage by its emergence from a PVL-positive MSSA ancestor from North Africa or Europe. The CC152 lineage has acquired SCCmec several times, but acquisition of SCCmec type V (5C2&5) seems associated with expansion of MRSA CC152 in Europe. IMPORTANCE Understanding the evolution of CA-MRSA is important in light of the increasing importance of this reservoir in the dissemination of MRSA. Here, we highlight the story of the CA-MRSA CC152 lineage using whole-genome sequencing on an international collection of CC152. We show that the evolution of this lineage is novel and that antibiotic usage may have the potential to select for the phage-encoded Panton-Valentine leukocidin. The diversity of the strains correlated highly to geography, with higher level of resistance observed among the European MRSA isolates. The mobility of the SCCmec element is mandatory for the emergence of novel MRSA lineages, and we show here distinct acquisitions, one of which is linked to the successful clone found throughout Europe today.

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Draft Genome Sequences of Eight Community-Associated Methicillin-Resistant Staphylococcus aureus Strains

Microbiology Resource Announcements ◽

10.1128/mra.00929-21 ◽

2021 ◽

Vol 10 (46) ◽

Author(s):

Kidon Sung ◽

Dereje D. Gudeta ◽

Miseon Park ◽

Paula Snippes Vagnone ◽

Mohamed S. Nawaz ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Draft Genome ◽

The United States ◽

Sequence Type ◽

Genome Sequences ◽

Methicillin Resistant ◽

Content Type ◽

Panton Valentine Leukocidin ◽

Valentine Leukocidin

Here, we report the draft genome sequences of eight community-associated methicillin-resistant Staphylococcus aureus strains that were resistant to cefoxitin, ampicillin, and erythromycin. Three isolates, i.e., CAR1, CAR2, and CAR8, were sequence type 8 (ST8) with staphylococcal cassette chromosome mec (SCC mec ) type IVa and were Panton-Valentine leukocidin (PVL) positive, which has been known as a predominant clone in the United States.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01560-19 ◽

2019 ◽

Vol 63 (11) ◽

Cited By ~ 2

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.

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Transmission and Persistence of Livestock-Associated Methicillin-Resistant Staphylococcus aureus among Veterinarians and Their Household Members

Applied and Environmental Microbiology ◽

10.1128/aem.02803-14 ◽

2014 ◽

Vol 81 (1) ◽

pp. 124-129 ◽

Cited By ~ 18

Author(s):

T. Bosch ◽

E. Verkade ◽

M. van Luit ◽

F. Landman ◽

J. Kluytmans ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Genotypic Variation ◽

Methicillin Resistant ◽

Content Type ◽

Genome Maps ◽

Household Members ◽

Mrsa Strains ◽

Prospective Longitudinal

ABSTRACTAfter the first isolation of livestock-associated methicillin-resistantStaphylococcus aureus(LA-MRSA) in 2003, this MRSA variant quickly became the predominant MRSA obtained from humans as part of the Dutch national MRSA surveillance. Previous studies have suggested that human-to-human transmission of LA-MRSA, compared to that of other MRSA lineages, rarely occurs. However, these reports describe the transmission of LA-MRSA based on epidemiology and limited molecular characterization of isolates, making it difficult to assess whether transmission actually occurred. In this study, we used whole-genome maps (WGMs) to identify possible transmission of LA-MRSA between humans. For this, we used LA-MRSA isolates originating from a 2-year prospective longitudinal cohort study in which livestock veterinarians and their household members were repeatedly sampled for the presence ofS. aureus. A considerable degree of genotypic variation among LA-MRSA strains was observed. However, there was very limited variability between the maps of the isolates originating from the same veterinarian, indicating that each of the veterinarians persistently carried or had reacquired the same LA-MRSA strain. Comparison of WGMs revealed that LA-MRSA transmission had likely occurred within virtually every veterinarian household. Yet only a single LA-MRSA strain per household appeared to be involved in transmission. The results corroborate our previous finding that LA-MRSA is genetically diverse. Furthermore, this study shows that transmission of LA-MRSA between humans occurs and that carriage of LA-MRSA can be persistent, thus posing a potential risk for spread of this highly resistant pathogen in the community.

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Antimicrobial Susceptibility Profiles of Staphylococcus aureus Isolates Recovered from Humans, Environmental Surfaces, and Companion Animals in Households of Children with Community-Onset Methicillin-Resistant S. aureus Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01492-15 ◽

2015 ◽

Vol 59 (10) ◽

pp. 6634-6637 ◽

Cited By ~ 6

Author(s):

John J. Morelli ◽

Patrick G. Hogan ◽

Melanie L. Sullivan ◽

Carol E. Muenks ◽

Jeffrey W. Wang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Susceptibility ◽

Companion Animals ◽

Methicillin Resistant ◽

Content Type ◽

Environmental Surfaces ◽

Household Members ◽

Outpatient Settings ◽

Susceptibility Profiles ◽

Community Onset

ABSTRACTOur objective was to determine the antibiotic susceptibility profiles ofStaphylococcus aureusisolates recovered from 110 households of children with community-onset methicillin-resistantS. aureus(MRSA) infections. Cultures were obtained from household members, household objects, and dogs and cats, yielding 1,633S. aureusisolates. TheS. aureusisolates were heterogeneous, although more than half were methicillin resistant. The highest proportion of MRSA was found in bathrooms. The majority of isolates were susceptible to antibiotics prescribed in outpatient settings.

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