Rapid Emergence and Evolution of Staphylococcus aureus Clones HarboringfusC-Containing Staphylococcal Cassette Chromosome Elements

ABSTRACTThe prevalence of fusidic acid (FA) resistance amongStaphylococcus aureusstrains in New Zealand (NZ) is among the highest reported globally, with a recent study describing a resistance rate of approximately 28%. Three FA-resistantS. aureusclones (ST5 MRSA, ST1 MSSA, and ST1 MRSA) have emerged over the past decade and now predominate in NZ, and in all three clones FA resistance is mediated by thefusCgene. In particular, ST5 MRSA has rapidly become the dominant MRSA clone in NZ, although the origin of FA-resistant ST5 MRSA has not been explored, and the genetic context offusCin FA-resistant NZ isolates is unknown. To better understand the rapid emergence of FA-resistantS. aureus, we used population-based comparative genomics to characterize a collection of FA-resistant and FA-susceptible isolates from NZ. FA-resistant NZ ST5 MRSA displayed minimal genetic diversity and represented a phylogenetically distinct clade within a global population model of clonal complex 5 (CC5)S. aureus. In all lineages,fusCwas invariably located within staphylococcal cassette chromosome (SCC) elements, suggesting that SCC-mediated horizontal transfer is the primary mechanism offusCdissemination. The genotypic association offusCwithmecAhas important implications for the emergence of MRSA clones in populations with high usage of fusidic acid. In addition, we found thatfusCwas colocated with a recently described virulence factor (tirS) in dominant NZS. aureusclones, suggesting a fitness advantage. This study points to the likely molecular mechanisms responsible for the successful emergence and spread of FA-resistantS. aureus.

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A Novel Staphylococcal Cassette Chromosomal Element, SCCfusC, CarryingfusCandspeGin Fusidic Acid-Resistant Methicillin-Resistant Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01772-13 ◽

2013 ◽

Vol 58 (2) ◽

pp. 1224-1227 ◽

Cited By ~ 13

Author(s):

Yu-Tzu Lin ◽

Jui-Chang Tsai ◽

Hsiao-Jan Chen ◽

Wei-Chun Hung ◽

Po-Ren Hsueh ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Fusidic Acid ◽

Methicillin Resistant Staphylococcus Aureus ◽

Nucleotide Sequencing ◽

Methicillin Resistant ◽

Content Type ◽

High Prevalence ◽

Flanking Regions ◽

Staphylococcal Cassette Chromosome

ABSTRACTA high prevalence offusC(16/46, 59%) was found in fusidic acid-resistant methicillin-resistantStaphylococcus aureusisolates collected from 2008 to 2010. Nucleotide sequencing offusCand flanking regions revealed a novel staphylococcal cassette chromosome (SCC) structure, SCCfusC, which was integrated intorlmHand located upstream from SCCmec. The SCCfusCelement containedspeG, which may contribute to the polyamine resistance.

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Serotype Emergence and Genotype Distribution among Macrolide-Resistant Invasive Streptococcus Pneumoniae Isolates in the Postconjugate Vaccine (PCV-7) Era

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05122-11 ◽

2011 ◽

Vol 56 (2) ◽

pp. 743-750 ◽

Cited By ~ 12

Author(s):

Zhenying Liu ◽

Irving Nachamkin ◽

Paul H. Edelstein ◽

Ebbing Lautenbach ◽

Joshua P. Metlay

Keyword(s):

Streptococcus Pneumoniae ◽

Gel Electrophoresis ◽

Molecular Mechanisms ◽

Population Based ◽

Resistance Rate ◽

Pulsed Field Gel Electrophoresis ◽

Genotype Distribution ◽

Erythromycin Resistance ◽

Content Type ◽

Pneumococcal Bacteremia

ABSTRACTWe conducted population-based surveillance for pneumococcal bacteremia within a 5-county region surrounding Philadelphia from October 2001 through September 2008, the period following introduction of the seven-valent pneumococcal conjugate vaccine. Erythromycin resistance increased from 14.7% in 2001-2002 to 20.3% in 2007-2008, while the resistance rate to penicillin (MIC, ≥2 μg/ml) decreased from 7.2% to 4.2% during the same period. The most predominant serotypes associated with erythromycin resistance in 2007-2008 included 19A (29.7%), 15A (29.2%), 6C (10.1%), 3 (5.6%), and 6A (4.5%). The molecular mechanisms for the increasing erythromycin resistance were mainly due to the growing presence ofmef(A)negativeerm(B)+andmef(A)+erm(B)+genotypes, which increased from 20.0% to 46.1% and from 1.8% to 19.1%, respectively, from 2001-2002 to 2007-2008. However,mef(A)-mediated erythromycin resistance decreased from 72.7% in 2001-2002 to 34.8% in 2007-2008. Serotypes related to theerm(B) gene were 15A (45.6%), 19A (20.9%), 3 (10.1%), and 6B (6.3%); serotypes related to themef(A)gene were 6A (18.6%), 19A (15.0%), 6C (9.3%), and 14(8.4%); serotypes associated with the presence of botherm(B) andmef(A)were 19A (81.5%), 15A (7.7%), and 19F (6.2%). Pulsed-field gel electrophoresis analysis demonstrated that erythromycin-resistant isolates within the 19A serotype were genetically diverse and related to several circulating international clones. In contrast, erythromycin-resistant isolates within the 15A serotype consisted of clonally identical or closely related isolates.

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In VitroEfficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01236-13 ◽

2013 ◽

Vol 57 (11) ◽

pp. 5717-5720 ◽

Cited By ~ 31

Author(s):

Hung-Jen Tang ◽

Chi-Chung Chen ◽

Kuo-Chen Cheng ◽

Kuan-Ying Wu ◽

Yi-Chung Lin ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Fusidic Acid ◽

Antibacterial Activities ◽

Methicillin Resistant ◽

Content Type ◽

Biofilm Model ◽

Rifampin Resistance ◽

Combination Regimens ◽

Resistant Mutation

ABSTRACTTo compare thein vitroantibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistantStaphylococcus aureus(MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.

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Complete Genome Sequence of Systemically Disseminated Sequence Type 8 Staphylococcal Cassette Chromosome mec Type IVl Community-Acquired Methicillin-Resistant Staphylococcus aureus

Genome Announcements ◽

10.1128/genomea.00852-17 ◽

2017 ◽

Vol 5 (35) ◽

Cited By ~ 4

Author(s):

Junzo Hisatsune ◽

Hideharu Hagiya ◽

Sumiko Shiota ◽

Motoyuki Sugai

Keyword(s):

Staphylococcus Aureus ◽

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Methicillin Resistant Staphylococcus Aureus ◽

Sequence Type ◽

Methicillin Resistant ◽

Content Type ◽

Staphylococcal Cassette Chromosome ◽

Epidermal Cell Differentiation

ABSTRACT Staphylococcus aureus JH4899, a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate collected from a patient with systematically disseminated infection, is classified as sequence type 8 and carries the staphylococcal cassette chromosome mec type IVl (SCCmecIVl). It produces TSST-1, SEC, a newly discovered enterotoxin (SE1), and epidermal cell differentiation inhibitor A (EDIN-A). Here, we present the complete genome sequence of the chromosome and a plasmid harboring the se1 and ednA genes.

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Advanced Resistance Studies Identify Two Discrete Mechanisms in Staphylococcus aureus to Overcome Antibacterial Compounds that Target Biotin Protein Ligase

Antibiotics ◽

10.3390/antibiotics9040165 ◽

2020 ◽

Vol 9 (4) ◽

pp. 165 ◽

Cited By ~ 1

Author(s):

Andrew J. Hayes ◽

Jiulia Satiaputra ◽

Louise M. Sternicki ◽

Ashleigh S. Paparella ◽

Zikai Feng ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Transcriptional Repression ◽

Molecular Mechanisms ◽

Resistance Mechanism ◽

Resistance Mechanisms ◽

Resistance Rate ◽

Biotin Protein Ligase ◽

Essential Enzyme

Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically important methicillin-resistant Staphylococcus aureus (S. aureus). In S. aureus, BPL is a bifunctional protein responsible for enzymatic biotinylation of two biotin-dependent enzymes, as well as serving as a transcriptional repressor that controls biotin synthesis and import. In this report, we investigate the mechanisms of action and resistance for a potent anti-BPL, an antibacterial compound, biotinyl-acylsulfamide adenosine (BASA). We show that BASA acts by both inhibiting the enzymatic activity of BPL in vitro, as well as functioning as a transcription co-repressor. A low spontaneous resistance rate was measured for the compound (<10−9) and whole-genome sequencing of strains evolved during serial passaging in the presence of BASA identified two discrete resistance mechanisms. In the first, deletion of the biotin-dependent enzyme pyruvate carboxylase is proposed to prioritize the utilization of bioavailable biotin for the essential enzyme acetyl-CoA carboxylase. In the second, a D200E missense mutation in BPL reduced DNA binding in vitro and transcriptional repression in vivo. We propose that this second resistance mechanism promotes bioavailability of biotin by derepressing its synthesis and import, such that free biotin may outcompete the inhibitor for binding BPL. This study provides new insights into the molecular mechanisms governing antibacterial activity and resistance of BPL inhibitors in S. aureus.

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Rapid Emergence of Resistance to Linezolid and Mutator Phenotypes in Staphylococcus aureus Isolates from an Adult Cystic Fibrosis Patient

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01392-13 ◽

2013 ◽

Vol 57 (10) ◽

pp. 5186-5188 ◽

Cited By ~ 11

Author(s):

Asmaa Tazi ◽

Jeanne Chapron ◽

Gerald Touak ◽

Magalie Longo ◽

Dominique Hubert ◽

...

Keyword(s):

Cystic Fibrosis ◽

Staphylococcus Aureus ◽

Cystic Fibrosis Patient ◽

Therapeutic Option ◽

Clinical Isolates ◽

23S Rrna ◽

Mutator Phenotype ◽

Content Type ◽

Emergence Of Resistance ◽

Rapid Emergence

ABSTRACTLinezolid has emerged as an important therapeutic option for the treatment ofStaphylococcus aureusin patients with cystic fibrosis. We report the rapid emergence, upon treatment with linezolid, of linezolid-resistantS. aureusclinical isolates through the accumulation of resistance-associated 23S rRNA mutations, together with acquisition of an altered mutator phenotype.

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Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00463-16 ◽

2016 ◽

Vol 60 (10) ◽

pp. 5957-5967 ◽

Cited By ~ 39

Author(s):

Katrin Schilcher ◽

Federica Andreoni ◽

Vanina Dengler Haunreiter ◽

Kati Seidl ◽

Barbara Hasse ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Treatment ◽

Molecular Mechanisms ◽

Treatment Strategies ◽

Extracellular Dna ◽

Content Type ◽

Transcriptional Stress ◽

Sigma Factor B ◽

Subinhibitory Concentrations ◽

Biofilm Matrix

ABSTRACTStaphylococcus aureusbiofilms are extremely difficult to treat. They provide a protected niche for the bacteria, rendering them highly recalcitrant toward host defenses as well as antibiotic treatment. Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response inS. aureusvia the alternative sigma factor B (σB) and upregulated the expression of the major biofilm-associated genesatlA,lrgA,agrA, thepsmgenes,fnbA, andfnbB. Our data suggest that subinhibitory concentrations of clindamycin alter the ability ofS. aureusto form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associatedS. aureusinfections.

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Novel Type XII Staphylococcal Cassette ChromosomemecHarboring a New Cassette Chromosome Recombinase, CcrC2

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01692-15 ◽

2015 ◽

Vol 59 (12) ◽

pp. 7597-7601 ◽

Cited By ~ 58

Author(s):

Zhaowei Wu ◽

Fan Li ◽

Dongliang Liu ◽

Huping Xue ◽

Xin Zhao

Keyword(s):

United States ◽

Staphylococcus Aureus ◽

Methicillin Resistance ◽

The United States ◽

Gene Complex ◽

Coagulase Negative Staphylococci ◽

Typing Method ◽

Content Type ◽

Staphylococcal Cassette Chromosome ◽

Sequence Identities

ABSTRACTExcision and integration of staphylococcal cassette chromosomemec(SCCmec) are mediated by cassette chromosome recombinases (Ccr), which play a crucial role in the worldwide spread of methicillin resistance in staphylococci. We report a novelccrgene,ccrC2, in the SCCmecof aStaphylococcus aureusisolate, BA01611, which showed 62.6% to 69.4% sequence identities to all publishedccrC1sequences. A further survey found that theccrC2gene was mainly located among coagulase-negative staphylococci (CoNS) and could be found in staphylococcal isolates from China, the United States, France, and Germany. Theccrgene complex harboring theccrC2gene was designated a type 9 complex, and the SCCmecof BA01611 was considered a novel type and was designated type XII (9C2). This novel SCCmecelement in BA01611 was flanked by a pseudo-SCC element (ΨSCCBA01611) carrying a truncatedccrA1gene. Both individual SCC elements and a composite SCC were excised from the chromosome based on detection of extrachromosomal circular intermediates. We advocate inclusion of the ccrC2gene and type 9ccrgene complex during revision of the SCCmectyping method.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01475-10 ◽

2011 ◽

Vol 55 (6) ◽

pp. 3046-3050 ◽

Cited By ~ 96

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.

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A Staphylococcus xylosus Isolate with a NewmecCAllotype

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01882-12 ◽

2012 ◽

Vol 57 (3) ◽

pp. 1524-1528 ◽

Cited By ~ 49

Author(s):

Ewan M. Harrison ◽

Gavin K. Paterson ◽

Matthew T. G. Holden ◽

Fiona J. E. Morgan ◽

Anders Rhod Larsen ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Content Type ◽

Staphylococcus Xylosus ◽

Novel Variant ◽

Staphylococcal Cassette Chromosome ◽

Class E

ABSTRACTRecently, a novel variant ofmecAknown asmecC(mecALGA251) was identified inStaphylococcus aureusisolates from both humans and animals. In this study, we identified aStaphylococcus xylosusisolate that harbors a new allotype of themecCgene,mecC1. Whole-genome sequencing revealed thatmecC1forms part of a class Emeccomplex (mecI-mecR1-mecC1-blaZ) located at theorfXlocus as part of a likely staphylococcal cassette chromosomemecelement (SCCmec) remnant, which also contains a number of other genes present on the type XI SCCmec.

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