scholarly journals Endovascular Infections Caused by Methicillin-Resistant Staphylococcus aureus Are Linked to Clonal Complex-Specific Alterations in Binding and Invasion Domains of Fibronectin-Binding Protein A as Well as the Occurrence offnbB

2015 ◽  
Vol 83 (12) ◽  
pp. 4772-4780 ◽  
Author(s):  
Yan Q. Xiong ◽  
Batu K. Sharma-Kuinkel ◽  
Nadia N. Casillas-Ituarte ◽  
Vance G. Fowler ◽  
Thomas Rude ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Amino Acid ◽  
Cell Invasion ◽  
Clonal Complex ◽  
Host Cells ◽  
Dynamic Binding ◽  
Complementary Sequence ◽  
Methicillin Resistant ◽  
Content Type ◽  
Fibronectin Binding

Endovascular infections caused byStaphylococcus aureusinvolve interactions with fibronectin present as extracellular matrix or surface ligand on host cells. We examined the expression, structure, and binding activity of the two majorS. aureusfibronectin-binding proteins (FnBPA, FnBPB) in 10 distinct, methicillin-resistant clinical isolates from patients with either persistent or resolving bacteremia. The persistent bacteremia isolates (n= 5) formed significantly stronger bonds with immobilized fibronectin as determined by dynamic binding measurements performed with atomic force microscopy. Several notable differences were also observed when the results were grouped by clonal complex 5 (CC5) strains (n= 5) versus CC45 strains (n= 5). Fibronectin-binding receptors on CC5 formed stronger bonds with immobilized fibronectin (P< 0.001). ThefnbAgene was expressed at higher levels in CC45, whereasfnbBwas found in only CC5 isolates. ThefnbBgene was not sequenced because all CC45 isolates lacked this gene. Instead, comparisons were made forfnbA, which was present in all 10 isolates. Sequencing offnbArevealed discrete differences within high-affinity, fibronectin-binding repeats (FnBRs) of FnBPA that included (i) 5-amino-acid polymorphisms in FnBR-9, FnBR-10, and FnBR-11 involving charged or polar side chains, (ii) an extra, 38-amino-acid repeat inserted between FnBR-9 and FnBR-10 exclusively seen in CC45 isolates, and (iii) CC5 isolates had the SVDFEED epitope in FnBR-11 (a sequence shown to be essential for fibronectin binding), while this sequence was replaced in all CC45 isolates with GIDFVED (a motif known to favor host cell invasion at the cost of reduced fibronectin binding). These complementary sequence and binding data suggest that differences infnbAandfnbB, particularly polymorphisms and duplications in FnBPA, giveS. aureustwo distinct advantages in human endovascular infections: (i) FnBPs similar to that of CC5 enhance ligand binding and foster initiation of disease, and (ii) CC45-like FnBPs promote cell invasion, a key attribute in persistent endovascular infections.

scholarly journals The basis of α-hemolysis Negative Methicillin-resistant Staphylococcus Aureus Isolates from Beijing Children’s Hospital

2021 ◽  
Author(s):  
Lijuan Wang ◽  
Chen Sun ◽  
Suyun Qian ◽  
Yingchao Liu ◽  
Kaihu Yao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Amino Acid ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clonal Complex ◽  
Common Mutation ◽  
Rna Expression ◽  
Single Mutation ◽  
Methicillin Resistant ◽  
Significant Difference ◽  
Important Virulence Factor

Abstract Background. Methicillin-resistant Staphylococcus aureus (MRSA) Clonal Complex 59 (CC59) clone has spread among Chinese children, resulting in many Staphylococcus aureus infections. α-hemolysin (Hlα) is an important virulence factor of Staphylococcus aureus, but little research has been done on CC59 isolates with negative α-hemolysis. Results. During the 4 periods (2009-2011, 2012-2013, 2016, 2017), 291 MRSA isolates were collected. Isolates with β and δ hemolysis accounted for 60.47% among the MRSA isolates in 2009-2011; 56.41% in 2012-2013; 77.14% in 2016; and 56.25% in 2017. most ST59 isolates (94.38%), 9 ST338 isolates (100%) showed β and δ hemolysis, both ST59 and ST338 clone belong to CC59 clone. Twenty-two ST239 isolates (73.33%), 8 ST88 isolates (80%), 4 ST5 isolates (100%), 13 ST22 isolates (92.86%) and 6 ST398 isolates (85.71%) showed α and δ hemolysis. α hemolysin in most clinical isolates is highly conservative, each showed one amino acid locus variation, the most common mutation was threonine at position 275 instead of isoleucine, then glutamic acid replaced aspartic acid at 208. Seventeen ST59 and 2 ST338 isolates had no mutation, 3 ST59 isolates showed single mutation (C448G), and only one ST59 isolate showed multilocus mutation. Other ST typing, such as ST1, ST5, ST88, ST20, ST239 and ST398, all had multilocus mutations, sites were from 3 to 8, no conservative sequence was found among isolates with the same ST typing. The carrying rates of RNA III, Rot, agrA, SarR, SarU and SigB were all over 93%, the carrying rates of SarZ and SarA genes were 41.86% and 34.88% respectively. Trancriptional levels of hlα in isolates showed α and δ hemolysis and β and δ hemolysis were equal. USA300 and R23 produced Hlα, R23 didn’t showed α hemolysis phenotype.Conclusions. Most clinical CC59 isolates from children in China were α hemolysis negative. There was no statistically significant difference in hlα gene and RNA expression, they produced the protein. The reason for the phenotypic deletion probably related to β hemolysin (Hlβ).

scholarly journals Susceptibility of Methicillin-Resistant Staphylococcus aureus to Five Quinazolinone Antibacterials

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Yuanyuan Qian ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Amino Acid ◽  
Binding Proteins ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Penicillin Binding Proteins

ABSTRACT The in vitro activities of five quinazolinone antibacterials, compounds Q1 to Q5, were tested against 210 strains of methicillin-resistant Staphylococcus aureus (MRSA). The MIC50/MIC90 values (in μg/ml) were as follows: Q1, 0.5/2; Q2, 1/4; Q3, 2/4; Q4, 0.06/0.25; and Q5, 0.125/0.5. Several strains with high MIC values (from 8 to >32 μg/ml) for some of these compounds exhibited amino acid changes in the penicillin-binding proteins, which are targeted by these antibacterials.

scholarly journals Toxic Shock Syndrome Toxin 1-Producing Methicillin-Resistant Staphylococcus aureus of Clonal Complex 5, the New York/Japan Epidemic Clone, Causing a High Early-Mortality Rate in Patients with Bloodstream Infections

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Dokyun Kim ◽  
Jun Sung Hong ◽  
Eun-Jeong Yoon ◽  
Hyukmin Lee ◽  
Young Ah Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
New York ◽  
Staphylococcus Aureus ◽  
Mortality Rate ◽  
Clonal Complex ◽  
Bloodstream Infections ◽  
Early Mortality ◽  
Epidemic Clone ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACT This study was performed to evaluate the clinical impacts of putative risk factors in patients with Staphylococcus aureus bloodstream infections (BSIs) through a prospective, multicenter, observational study. All 567 patients with S. aureus BSIs that occurred during a 1-year period in six general hospitals were included in this study. Host- and pathogen-related variables were investigated to determine risk factors for the early mortality of patients with S. aureus BSIs. The all-cause mortality rate was 15.0% (85/567) during the 4-week follow-up period from the initial blood culture, and 76.5% (65/85) of the mortality cases occurred within the first 2 weeks. One-quarter (26.8%, 152/567) of the S. aureus blood isolates carried the tst-1 gene, and most (86.2%, 131/152) of them were identified to be clonal complex 5 agr type 2 methicillin-resistant S. aureus (MRSA) strains harboring staphylococcal cassette chromosome mec type II, belonging to the New York/Japan epidemic clone. A multivariable logistic regression showed that the tst-1 positivity of the causative S. aureus isolates was associated with an increased 2-week mortality rate both in patients with S. aureus BSIs (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 0.90 to 2.88) and in patients with MRSA BSIs (aOR, 2.61; 95% CI, 1.19 to 6.03). Two host-related factors, an increased Pitt bacteremia score and advanced age, as well as a pathogen-related factor, carriage of tst-1 by causative MRSA isolates, were risk factors for 2-week mortality in patients with BSIs. Careful management of patients with BSIs caused by the New York/Japan epidemic clone is needed to improve clinical outcomes.

scholarly journals Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and β-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Selvi C. Ersoy ◽  
Mariam Otmishi ◽  
Vanessa T. Milan ◽  
Liang Li ◽  
Youngju Pak ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clonal Complex ◽  
Population Analysis ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mueller Hinton ◽  
Testing Medium ◽  
Mrsa Strains ◽  
Mueller Hinton Broth

ABSTRACT Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic β-lactam MICs in standard Mueller-Hinton broth (MHB) nor population analysis profiles were predictive of this phenotype. Several genotypic markers (clonal complex 8 [CC8]; agr I and spa t008) were associated with NaHCO3 responsiveness for OXA.

scholarly journals Novel Types of Staphylococcal Cassette ChromosomemecElements Identified in Clonal Complex 398 Methicillin-Resistant Staphylococcus aureus Strains

2011 ◽  
Vol 55 (6) ◽  
pp. 3046-3050 ◽  
Author(s):  
Shanshuang Li ◽  
Robert Leo Skov ◽  
Xiao Han ◽  
Anders Rhod Larsen ◽  
Jesper Larsen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clonal Complex ◽  
Subtype C ◽  
Methicillin Resistant ◽  
Content Type ◽  
Original Host ◽  
Mrsa Strains ◽  
Type V ◽  
Staphylococcal Cassette Chromosome

ABSTRACTThe structures of staphylococcal cassette chromosomemec(SCCmec) elements carried by 31 clonal complex 398 (CC398) methicillin-resistantStaphylococcus aureus(MRSA) strains isolated from the participants at a conference were analyzed. The SCCmecs were classified into novel types, namely, IX, X, V(5C2&5) subtype c, and IVa. Type V(5C2&5) subtype c, IX, and X SCCmecs carried genes conferring resistance to metals. The structures of SCCmecs from CC398 strains were distinct from those normally found in humans, adding to the evidence that humans are not the original host for CC398.

scholarly journals New Transposon Tn6133in Methicillin-Resistant Staphylococcus aureus ST398 Containsvga(E), a Novel Streptogramin A, Pleuromutilin, and Lincosamide Resistance Gene

2011 ◽  
Vol 55 (10) ◽  
pp. 4900-4904 ◽  
Author(s):  
Sybille Schwendener ◽  
Vincent Perreten
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Amino Acid ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Transporter Family ◽  
Acid Protein ◽  
Mrsa St398 ◽  
Amino Acid Protein

ABSTRACTA novel streptogramin A, pleuromutilin, and lincosamide resistance determinant, Vga(E), was identified in porcine methicillin-resistantStaphylococcus aureus(MRSA) ST398. Thevga(E) gene encoded a 524-amino-acid protein belonging to the ABC transporter family. It was found on a multidrug resistance-conferring transposon, Tn6133, which was comprised of Tn554with a stably integrated 4,787-bp DNA sequence harboringvga(E). Detection of Tn6133in several porcine MRSA ST398 isolates and its ability to circularize suggest a potential for dissemination.

scholarly journals Prevalence and Genomic Structure of Bacteriophage phi3 in Human-Derived Livestock-Associated Methicillin-Resistant Staphylococcus aureus Isolates from 2000 to 2015

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Sarah van Alen ◽  
Britta Ballhausen ◽  
Ursula Kaspar ◽  
Robin Köck ◽  
Karsten Becker
Keyword(s):  
Staphylococcus Aureus ◽  
Clonal Complex ◽  
Genomic Structure ◽  
Animal Husbandry ◽  
Bacterial Attachment ◽  
University Hospital ◽  
Dense Area ◽  
Methicillin Resistant ◽  
Content Type ◽  
Human Host

ABSTRACT Whereas the emergence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 (CC398) in animal husbandry and its transmission to humans are well documented, less is known about factors driving the epidemic spread of this zoonotic lineage within the human population. One factor could be the bacteriophage phi3, which is rarely detected in S. aureus isolates from animals but commonly found among isolates from humans, including those of the human-adapted methicillin-susceptible S. aureus (MSSA) CC398 clade. The proportion of phi3-carrying MRSA spa-CC011 isolates, which constitute presumptively LA-MRSA within the multilocus sequence type (MLST) clonal complex 398, was systematically assessed for a period of 16 years to investigate the role of phi3 in the adaptation process of LA-MRSA to the human host. For this purpose, 632 MRSA spa-CC011 isolates from patients of a university hospital located in a pig farming-dense area in Germany were analyzed. Livestock-associated acquisition of MRSA spa-CC011 was previously reported as having increased from 1.8% in 2000 to 29.4% in 2014 in MRSA-positive patients admitted to this hospital. However, in this study, the proportion of phi3-carrying isolates rose only from 1.1% (2000 to 2006) to 3.9% (2007 to 2015). Characterization of the phi3 genomes revealed 12 different phage types ranging in size from 40,712 kb up to 44,003 kb, with four hitherto unknown integration sites (genes or intergenic regions) and several modified bacterial attachment (attB) sites. In contrast to the MSSA CC398 clade, phi3 acquisition seems to be no major driver for the readaptation of MRSA spa-CC011 to the human host.

scholarly journals A Clonal Complex 12 Methicillin-Resistant Staphylococcus aureus Strain, West Australian MRSA-59, Harbors a Novel Pseudo-SCCmecElement

2015 ◽  
Vol 59 (11) ◽  
pp. 7142-7144 ◽  
Author(s):  
Stefan Monecke ◽  
Geoffrey W. Coombs ◽  
Julie Pearson ◽  
Helmut Hotzel ◽  
Peter Slickers ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clonal Complex ◽  
Copper Resistance ◽  
Aureus Strain ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Reading Frame ◽  
Link Type

ABSTRACTA West Australian methicillin-resistantStaphylococcus aureusstrain (WA MRSA-59) was characterized by microarray and sequencing. Its pseudo-staphylococcal cassette chromosomemec(SCCmec) element compriseddcs,Q9XB68-dcs,mvaS-SCC,Q5HJW6,dru,ugpQ,ydeM,mecA-mecR-mecI, txbimecI,tnpIS431,copA2-mco(copper resistance),ydhK,arsC-arsB-arsR(arsenic resistance), open reading frame PT43, andper-2. Recombinase genes,xylR(mecR2), and PSM-mec(phenol-soluble modulin) were absent. We suggest thatmeccomplex A should be split into two subtypes. One harbors PSM-mecandxylR(mecR2). It is found in SCCmectypes II, III, and VIII. The second subtype, described herein, is present in WA MRSA-59 and some coagulase-negative staphylococci.

scholarly journals Complete Genome Sequences of Canadian Epidemic Methicillin-Resistant Staphylococcus aureus Strains CMRSA3 and CMRSA6

2018 ◽  
Vol 7 (5) ◽  
Author(s):  
Jo-Ann McClure ◽  
Steven M. Shideler ◽  
Kunyan Zhang
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clonal Complex ◽  
Virulent Strain ◽  
Sequence Type ◽  
Genome Sequences ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Strains ◽  
Highly Virulent

Methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 8 (CC8) sequence type 239 (ST239) represents a predominant hospital-associated MRSA sublineage present worldwide. The Canadian epidemic MRSA strains CMRSA3 and CMRSA6 are moderately virulent members of this group but are closely related to the highly virulent strain TW20.

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

mSphere ◽  
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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