A Yersiniabactin-producing Klebsiella aerogenes Strain Causing an Outbreak in an Austrian Neonatal Intensive Care Unit

Background: Yersiniabactin, a siderophore with a high affinity to iron, has been described as a potential virulence factor in Enterobacteriaceae. Klebsiella aerogenes is a Gram-negative rod known to cause invasive infection in very low birth weight infants but is an unusual pathogen to cause outbreaks in neonatal intensive care units (NICU). Methods: We performed a retrospective analysis of all patients colonized with K. aerogenes in our NICU from September to December 2018. Each infant with an occurrence of K. aerogenes in any microbiological culture was defined as a case. Clinical data were taken from medical charts. K. aerogenes isolates were genotyped using whole-genome sequencing combined with core genome multilocus sequencing type analysis. Yersiniabactin production was evaluated by luciferase assay. Results: In total 16 patients were colonized with K. aerogenes over the 3-month period and 13 patients remained asymptomatic or developed late-onset neonatal sepsis from another pathogen. Three patients developed necrotizing enterocolitis, 2 complicated by sepsis and 1 of them died. All symptomatic patients were premature infants with low birth weight. Genetic sequencing confirmed an outbreak with the same strain, all samples expressed the high-pathogenicity island, necessary for the production of yersiniabactin. Six exemplary cases were proven to produce yersiniabactin in vitro. Conclusion: This is the first report of an outbreak of a yersiniabactin-producing K. aerogenes strain causing invasive infection in preterm infants. We hypothesize that, due to improved iron uptake, this strain was associated with higher virulence than non-yersiniabactin-producing strains. Extended search for virulence factors and genetic sequencing could be pivotal in the management of NICU outbreaks in the future.

[1]  S. Garneau‐Tsodikova,et al.  Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts , 2021, Proceedings of the National Academy of Sciences.

[2]  M. Caplan,et al.  Defining necrotizing enterocolitis: current difficulties and future opportunities , 2020, Pediatric Research.

[3]  H. Boskabadi,et al.  Etiology, clinical findings and laboratory parameters in neonates with acute bacterial meningitis , 2020, Iranian journal of microbiology.

[4]  J. Pagés,et al.  Enterobacter spp.: Update on Taxonomy, Clinical Aspects, and Emerging Antimicrobial Resistance , 2019, Clinical Microbiology Reviews.

[5]  B. Bohnhorst,et al.  Prospective surveillance of bacterial colonization and primary sepsis: findings of a tertiary neonatal intensive and intermediate care unit. , 2019, The Journal of hospital infection.

[6]  A. Berger,et al.  Outbreak of Yersiniabactin-producing Klebsiella pneumoniae in a Neonatal Intensive Care Unit. , 2019, The Pediatric infectious disease journal.

[7]  A. Manges,et al.  Contribution of yersiniabactin to the virulence of an Escherichia coli sequence type 69 ("clonal group A") cystitis isolate in murine models of urinary tract infection and sepsis. , 2018, Microbial pathogenesis.

[8]  K. Holt,et al.  Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations , 2018, Microbial genomics.

[9]  Asad U. Khan,et al.  Detection of New Delhi Metallo-β-Lactamase Variants NDM-4, NDM-5, and NDM-7 in Enterobacter aerogenes Isolated from a Neonatal Intensive Care Unit of a North India Hospital: A First Report. , 2018, Microbial drug resistance.

[10]  K. Holt,et al.  Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination , 2017, bioRxiv.

[11]  C. Stief,et al.  The high-pathogenicity island (HPI) promotes flagellum-mediated motility in extraintestinal pathogenic Escherichia coli , 2017, PloS one.

[12]  C. Quach,et al.  Outbreaks in the neonatal ICU: a review of the literature. , 2017, Current opinion in infectious diseases.

[13]  N. Leal,et al.  Occurrence and analysis of irp2 virulence gene in isolates of Klebsiella pneumoniae and Enterobacter spp. from microbiota and hospital and community-acquired infections. , 2016, Microbial pathogenesis.

[14]  P. Andersen,et al.  Mapping the Evolution of Hypervirulent Klebsiella pneumoniae , 2015, mBio.

[15]  Jonathan Wilksch,et al.  Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health , 2015, Proceedings of the National Academy of Sciences.

[16]  W. Göpel,et al.  Risk for Late-onset Blood-culture Proven Sepsis in Very-low-birth Weight Infants Born Small for Gestational Age: A Large Multicenter Study from the German Neonatal Network , 2014, The Pediatric infectious disease journal.

[17]  J. Heesemann,et al.  The RNA Chaperone Hfq Impacts Growth, Metabolism and Production of Virulence Factors in Yersinia enterocolitica , 2014, PloS one.

[18]  Krinko Praktische Umsetzung sowie krankenhaushygienische und infektionspräventive Konsequenzen des mikrobiellen Kolonisationsscreenings bei intensivmedizinisch behandelten Früh- und Neugeborenen , 2013 .

[19]  Dmitry Antipov,et al.  Assembling Single-Cell Genomes and Mini-Metagenomes From Chimeric MDA Products , 2013, J. Comput. Biol..

[20]  J. Nougayrède,et al.  Interplay between Siderophores and Colibactin Genotoxin Biosynthetic Pathways in Escherichia coli , 2013, PLoS pathogens.

[21]  Jens Stoye,et al.  Updating benchtop sequencing performance comparison , 2013, Nature Biotechnology.

[22]  A. Rakin,et al.  Hunger for iron: the alternative siderophore iron scavenging systems in highly virulent Yersinia , 2012, Front. Cell. Inf. Microbio..

[23]  Sergey I. Nikolenko,et al.  SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing , 2012, J. Comput. Biol..

[24]  J. Kool,et al.  Investigation and Control of an Outbreak of Enterobacter aerogenes Bloodstream Infection in a Neonatal Intensive Care Unit in Fiji , 2009, Infection Control & Hospital Epidemiology.

[25]  B. Allegranzi,et al.  The World Health Organization Guidelines on Hand Hygiene in Health Care and Their Consensus Recommendations , 2009, Infection Control & Hospital Epidemiology.

[26]  Sylvain Brisse,et al.  Multilocus Sequence Typing of Klebsiella pneumoniae Nosocomial Isolates , 2005, Journal of Clinical Microbiology.

[27]  R. Baron,et al.  Épidémie à Enterobacter aerogenes en pédiatrie , 2004 .

[28]  R. Koczura,et al.  Yersiniabactin and other siderophores produced by clinical isolates of Enterobacter spp. and Citrobacter spp. , 2004, FEMS immunology and medical microbiology.

[29]  E. Denamur,et al.  Yersinia High-Pathogenicity Island Contributes to Virulence in Escherichia coli Causing Extraintestinal Infections , 2002, Infection and Immunity.

[30]  O. Clermont,et al.  The Yersinia high-pathogenicity island is highly predominant in virulence-associated phylogenetic groups of Escherichia coli. , 2001, FEMS microbiology letters.

[31]  J. Heesemann,et al.  High-pathogenicity island of Yersinia pestis in enterobacteriaceae isolated from blood cultures and urine samples: prevalence and functional expression. , 2000, The Journal of infectious diseases.

[32]  A. D. de Almeida,et al.  The Yersinia high-pathogenicity island is present in different members of the family Enterobacteriaceae. , 2000, FEMS microbiology letters.

[33]  M. Sredkova,et al.  [Nosocomial enterobacter - sepsis in neonatal intensive care unit in Pleven]. , 2000, Akusherstvo i ginekologiia.

[34]  Vikas Loiwal, Ajay Kumar, Piyush Gupta, Sunil Gomb Ramachandran Enterobacter aerogenes outbreak in a neonatal intensive care unit , 1999, Pediatrics international : official journal of the Japan Pediatric Society.

[35]  E. Wong,et al.  Risk factors for Enterobacter septicemia in a neonatal unit: case-control study. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[36]  P. Williams,et al.  Iron uptake mechanisms of pathogenic bacteria. , 1993, FEMS microbiology reviews.