Comparative Genomics Study of Staphylococcus epidermidis Isolates from Orthopedic-Device-Related Infections Correlated with Patient Outcome

Post, Virginia; Harris, Llinos G.; Morgenstern, Mario; Mageiros, Leonardos; Hitchings, Matthew D.; Méric, Guillaume; Pascoe, Ben; Sheppard, Samuel K.; Richards, R. Geoff; Moriarty, T. Fintan

doi:10.1128/jcm.00881-17

Cited by 56 publications

(63 citation statements)

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“…However, the Bap homologue termed bhp, is present in S. epidermidis [2]. Investigators in the developed countries found an association between presence of bhp and aacA [aac(6)-aph (2)] genes with the "not cured" clinical outcome among patients who underwent surgery and got infected by staphylococci [45].…”

Section: Discussionmentioning

confidence: 99%

Species and drug susceptibility profiles of staphylococci isolated from healthy children in Eastern Uganda

et al. 2020

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Staphylococci are a key component of the human microbiota, and they mainly colonize the skin and anterior nares. However, they can cause infection in hospitalized patients and healthy individuals in the community. Although majority of the Staphylococcus aureus strains are coagulase-positive, some do not produce coagulase, and the isolation of coagulase-positive non-S. aureus isolates in humans is increasingly being reported. Therefore, sound knowledge of the species and characteristics of staphylococci in a given setting is important, especially isolates from children and immunocompromised individuals. The spectrum of Staphylococcus species colonizing children in Uganda is poorly understood; here, we aimed to determine the species and characteristics of staphylococci isolated from children in Eastern Uganda. Seven hundred and sixty four healthy children less than 5 years residing in Iganga and Mayuge districts in Eastern Uganda were enrolled. A total of 513 staphylococci belonging to 13 species were isolated from 485 children (63.5%, 485/764), with S. aureus being the dominant species (37.6%, 193/513) followed by S. epidermidis (25.5%, 131/513), S. haemolyticus (2.3%, 12/513), S. hominis (0.8%, 4/513) and S. haemolyticus/lugdunensis (0.58%, 3/513). Twenty four (4.95%, 24/485) children were co-colonized by two or more Staphylococcus species. With the exception of penicillin, antimicrobial resistance (AMR) rates were low; all isolates were susceptible to vancomycin, teicoplanin, linezolid and daptomycin. The prevalence of methicillin resistance was 23.8% (122/513) and it was highest in S. haemolyticus (66.7%, 8/12) followed by S. aureus (28.5%, 55/193) and S. epidermidis (23.7%, 31/131). The prevalence of multidrug resistance was 20.3% (104/513), and 59% (72/122) of methicillin resistant staphylococci were multidrug resistant. Four methicillin susceptible S. aureus isolates and a methicillin resistant S. scuiri isolate were mupirocin resistant (high-level). The most frequent AMR genes were mecA, vanA, ant(4')-Ia, and aac(6')-Ie-aph(2'')-Ia, pointing to presence of AMR drivers in the community.

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Section: Discussionmentioning

confidence: 99%

Species and drug susceptibility profiles of staphylococci isolated from healthy children in Eastern Uganda

et al. 2020

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“…Genomes from 415 S. epidermidis isolates, from multiple sampling efforts, were analysed (Supplementary Data 2 ). These included: 240 isolates sampled as part of this study; 35 genomes available from public repositories (February 2013); and 140 recently sequenced S. epidermidis genomes from geographically and clinically diverse isolates characterised in previous studies 21 , 23 , 24 , 52 . Asymptomatic carriage isolates were sampled from healthy volunteers in Swansea University (UK) in 2012, using culture swabs containing Ames media, which were then cultured on Columbia Blood Agar plates.…”

Section: Methodsmentioning

confidence: 99%

Disease-associated genotypes of the commensal skin bacterium Staphylococcus epidermidis

et al. 2018

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Some of the most common infectious diseases are caused by bacteria that naturally colonise humans asymptomatically. Combating these opportunistic pathogens requires an understanding of the traits that differentiate infecting strains from harmless relatives. Staphylococcus epidermidis is carried asymptomatically on the skin and mucous membranes of virtually all humans but is a major cause of nosocomial infection associated with invasive procedures. Here we address the underlying evolutionary mechanisms of opportunistic pathogenicity by combining pangenome-wide association studies and laboratory microbiology to compare S. epidermidis from bloodstream and wound infections and asymptomatic carriage. We identify 61 genes containing infection-associated genetic elements (k-mers) that correlate with in vitro variation in known pathogenicity traits (biofilm formation, cell toxicity, interleukin-8 production, methicillin resistance). Horizontal gene transfer spreads these elements, allowing divergent clones to cause infection. Finally, Random Forest model prediction of disease status (carriage vs. infection) identifies pathogenicity elements in 415 S. epidermidis isolates with 80% accuracy, demonstrating the potential for identifying risk genotypes pre-operatively.

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“…A cutaneous S. epidermidis isolate containing qacA4 (Table S4) was identified from a CHG bathing pilot study (13) conducted at Seattle Children's Hospital. In addition, we searched through the sequence reads of 922 isolates deposited in the NCBI Sequence Read Archive as part of several large S. epidermidis sequencing projects (BioProject accession numbers PRJEB12090, PRJNA239883, PRJNA382527, PRJNA433155, PRJNA434275, PRJNA470534, and PRJNA470752) (29)(30)(31)(32)(33). We further queried the NCBI WGS database and all of the bacterial whole-genome sequencing data sets in the European Nucleotide Archive through December 2016 (34).…”

Section: Figmentioning

confidence: 99%

A Novel, Widespread qacA Allele Results in Reduced Chlorhexidine Susceptibility in Staphylococcus epidermidis

Addetia¹,

Greninger

Adler³

et al. 2019

Antimicrob Agents Chemother

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Chlorhexidine gluconate (CHG) is a topical antiseptic widely used in health care settings. In Staphylococcus spp., the pump QacA effluxes CHG, while the closely related QacB cannot due to a single amino acid substitution. We characterized 1,050 cutaneous Staphylococcus isolates obtained from 173 pediatric oncology patients enrolled in a multicenter CHG bathing trial. CHG susceptibility testing revealed that 63 (6%) of these isolates had elevated CHG MICs (≥4 μg/ml). Screening of all 1,050 isolates for the qacA/B gene (the same qac gene with A or B allele) by restriction fragment length polymorphism (RFLP) yielded 56 isolates with a novel qacA/B RFLP pattern, qacA/B273. The CHG MIC was significantly higher for qacA/B273-positive isolates (MIC50, 4 μg/ml; MIC range, 0.5 to 4 μg/ml) than for other qac groups: qacA-positive isolates (n = 559; MIC50, 1 μg/ml; MIC range, 0.5 to 4 μg/ml), qacB-positive isolates (n = 17; MIC50, 1 μg/ml; MIC range, 0.25 to 2 μg/ml), and qacA/B-negative isolates (n = 418, MIC50, 1 μg/ml; MIC range, 0.125 to 2 μg/ml) (P = 0.001). A high proportion of the qacA/B273-positive isolates also displayed methicillin resistance (96.4%) compared to the other qac groups (24.9 to 61.7%) (P = 0.001). Whole-genome sequencing revealed that qacA/B273-positive isolates encoded a variant of QacA with 2 amino acid substitutions. This new allele, named qacA4, was carried on the novel plasmid pAQZ1. The qacA4-carrying isolates belonged to the highly resistant Staphylococcus epidermidis sequence type 2 clone. By searching available sequence data sets, we identified 39 additional qacA4-carrying S. epidermidis strains from 5 countries. Curing an isolate of qacA4 resulted in a 4-fold decrease in the CHG MIC, confirming the role of qacA4 in the elevated CHG MIC. Our results highlight the importance of further studying qacA4 and its functional role in clinical staphylococci.

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Comparative Genomics Study of Staphylococcus epidermidis Isolates from Orthopedic-Device-Related Infections Correlated with Patient Outcome

Cited by 56 publications

References 56 publications

Species and drug susceptibility profiles of staphylococci isolated from healthy children in Eastern Uganda

Species and drug susceptibility profiles of staphylococci isolated from healthy children in Eastern Uganda

Disease-associated genotypes of the commensal skin bacterium Staphylococcus epidermidis

A Novel, Widespread qacA Allele Results in Reduced Chlorhexidine Susceptibility in Staphylococcus epidermidis

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