Whole-genome sequencing to explore nosocomial transmission and virulence in neonatal methicillin-susceptible Staphylococcus aureus bacteremia.

Bibi C G C Slingerland, Margreet C Vos, Willeke Bras, René F Kornelisse, Dieter De Coninck, Alex van Belkum, Irwin K M Reiss, Wil H F Goessens, Corné H W Klaassen, Nelianne J Verkaik
Author Information
  1. Bibi C G C Slingerland: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, GD, Rotterdam, The Netherlands. b.slingerland@erasmusmc.nl. ORCID
  2. Margreet C Vos: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, GD, Rotterdam, The Netherlands.
  3. Willeke Bras: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, GD, Rotterdam, The Netherlands.
  4. René F Kornelisse: Department of Pediatrics, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  5. Dieter De Coninck: BioMérieux SA, Data Analytics, Clinical Unit, Sint-Martens-Latem, Belgium.
  6. Alex van Belkum: BioMérieux SA, Clinical Unit, 38390, La Balme-les-Grottes, France.
  7. Irwin K M Reiss: Department of Pediatrics, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  8. Wil H F Goessens: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, GD, Rotterdam, The Netherlands.
  9. Corné H W Klaassen: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, GD, Rotterdam, The Netherlands.
  10. Nelianne J Verkaik: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, GD, Rotterdam, The Netherlands.

Abstract

BACKGROUND: Neonatal Staphylococcus aureus (S. aureus) bacteremia is an important cause of morbidity and mortality. In this study, we examined whether methicillin-susceptible S. aureus (MSSA) transmission and genetic makeup contribute to the occurrence of neonatal S. aureus bacteremia.
METHODS: A retrospective, single-centre study was performed. All patients were included who suffered from S. aureus bacteremia in the neonatal intensive care unit (NICU), Erasmus MC-Sophia, Rotterdam, the Netherlands, between January 2011 and November 2017. Whole-genome sequencing (WGS) was used to characterize the S. aureus isolates, as was also done in comparison to reference genomes. Transmission was considered likely in case of genetically indistinguishable S. aureus isolates.
RESULTS: Excluding coagulase-negative staphylococci (CoNS), S. aureus was the most common cause of neonatal bacteremia. Twelve percent (n = 112) of all 926 positive blood cultures from neonates grew S. aureus. Based on core genome multilocus sequence typing (cgMLST), 12 clusters of genetically indistinguishable MSSA isolates were found, containing 33 isolates in total (2-4 isolates per cluster). In seven of these clusters, at least two of the identified MSSA isolates were collected within a time period of one month. Six virulence genes were present in 98-100% of all MSSA isolates. In comparison to S. aureus reference genomes, toxin genes encoding staphylococcal enterotoxin A (sea) and toxic shock syndrome toxin 1 (tsst-1) were present more often in the genomes of bacteremia isolates.
CONCLUSION: Transmission of MSSA is a contributing factor to the occurrence of S. aureus bacteremia in neonates. Sea and tsst-1 might play a role in neonatal S. aureus bacteremia.

Keywords

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MeSH Term

Bacteremia
Bacterial Toxins
Bacterial Typing Techniques
Cross Infection
Enterotoxins
Female
Genome, Bacterial
Humans
Infant, Newborn
Intensive Care Units, Neonatal
Male
Multilocus Sequence Typing
Netherlands
Retrospective Studies
Staphylococcal Infections
Staphylococcus aureus
Superantigens
Virulence
Whole Genome Sequencing

Chemicals

Bacterial Toxins
Enterotoxins
Superantigens
enterotoxin F, Staphylococcal
enterotoxin A, Staphylococcal

Word Cloud

Created with Highcharts 10.0.0aureusSbacteremiaisolatesMSSAneonatalStaphylococcusWhole-genomesequencinggenomesTransmissionNeonatalcausestudymethicillin-susceptibletransmissionoccurrenceintensivecareunitcomparisonreferencegeneticallyindistinguishableneonatesclustersvirulencegenespresenttoxintsst-1BACKGROUND:importantmorbiditymortalityexaminedwhethergeneticmakeupcontributeMETHODS:retrospectivesingle-centreperformedpatientsincludedsufferedNICUErasmusMC-SophiaRotterdamNetherlandsJanuary2011November2017WGSusedcharacterizealsodoneconsideredlikelycaseRESULTS:Excludingcoagulase-negativestaphylococciCoNScommonTwelvepercentn = 112926positivebloodculturesgrewBasedcoregenomemultilocussequencetypingcgMLST12foundcontaining33total2-4perclustersevenleasttwoidentifiedcollectedwithintimeperiodonemonthSix98-100%encodingstaphylococcalenterotoxinseatoxicshocksyndrome1oftenCONCLUSION:contributingfactorSeamightplayroleexplorenosocomialBacteremia

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