Toxin-Producing Klebsiella oxytoca in Healthy Infants: Commensal or Pathobiont?
Journal
Journal of pediatric gastroenterology and nutrition
ISSN: 1536-4801
Titre abrégé: J Pediatr Gastroenterol Nutr
Pays: United States
ID NLM: 8211545
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
pubmed:
15
9
2021
medline:
26
2
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
Klebsiella oxytoca is a gastrointestinal pathobiont with the potential to produce the toxins tilivalline and tilimycin, which cause antibiotic-associated hemorrhagic colitis. Overgrowth of toxigenic K oxytoca has recently been implicated in necrotizing enterocolitis. K oxytoca colonizes 2-9% of healthy adults, however, there is no systematic data on colonization in healthy children. We investigated K oxytoca colonization and its toxigenic properties in healthy infants. We sampled stool of healthy infants and determined K oxytoca colonization using stool culture and PCR (pehX). Toxin in stool was measured with HPLC/high-resolution mass spectrometry. K oxytoca isolates were typed using multi-locus sequence typing (MLST) and K oxytoca toxin PCR (npsA/B). Cytotoxin production of isolates was analyzed by MTT assay. K oxytoca was detected in 30 of 61 infants (49%) using stool culture and in 45 of 61 (73%) using PCR (pehX). Toxin marker PCR (npsA/B) was positive in 66% of stool samples positive for K oxytoca PCR. Stool toxin levels were too low for quantitation but traces of tilivalline were detected. Contrarily, 49% of K oxytoca isolates demonstrated toxicity in the MTT assay. MLST revealed 36 distinct sequence types affiliated with all known K oxytoca sequence type clusters (A, B1 and B2). More than 70% of healthy infants were colonized with K oxytoca. Toxin quantities in stool of colonized healthy infants were below detection level, yet half of the isolates produced toxin in vitro demonstrating their pathobiont potential. The high occurrence of toxigenic K oxytoca in healthy infants has to be considered for future disease association studies.
Identifiants
pubmed: 34520403
doi: 10.1097/MPG.0000000000003299
pii: 00005176-202201000-00008
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1-e7Informations de copyright
Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Hogenauer C, Langner C, Beubler E, et al. Klebsiella oxytoca as a causative organism of antibiotic-associated hemorrhagic colitis. N Engl J Med 2006; 355:2418–2426.
Joainig MM, Gorkiewicz G, Leitner E, et al. Cytotoxic effects of Klebsiella oxytoca strains isolated from patients with antibiotic-associated hemorrhagic colitis or other diseases caused by infections and from healthy subjects. J Clin Microbiol 2010; 48:817–824.
Schneditz G, Rentner J, Roier S, et al. Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis. Proc Natl Acad Sci USA 2014; 111:13181–13186.
Unterhauser K, Poltl L, Schneditz G, et al. Klebsiella oxytoca enterotoxins tilimycin and tilivalline have distinct host DNA-damaging and microtubule-stabilizing activities. Proc Natl Acad Sci USA 2019; 116:3774–3783.
Hoffmann KM, Deutschmann A, Weitzer C, et al. Antibiotic-associated hemorrhagic colitis caused by cytotoxin-producing Klebsiella oxytoca . Pediatrics 2010; 125:e960–e963.
Youn Y, Lee SW, Cho HH, et al. Antibiotics-associated hemorrhagic colitis caused by Klebsiella oxytoca : two case reports. Pediatr Gastroenterol Hepatol Nutr 2018; 21:141–146.
Karimi A, Fayazi A, Ghorobi J, et al. A pediatric case of antibiotic-associated hemorrhagic colitis caused by Klebsiella oxytoca . Int J Prev Med 2019; 10:113.
Paveglio S, Ledala N, Rezaul K, et al. Cytotoxin-producing Klebsiella oxytoca in the preterm gut and its association with necrotizing enterocolitis. Emerg Microbes Infect 2020; 9:1321–1329.
Eberhart M, Grisold A, Lavorato M, et al. Extended-spectrum beta-lactamase (ESBL) producing Enterobacterales in stool surveillance cultures of preterm infants are no risk factor for necrotizing enterocolitis: a retrospective case-control study over 12 years. Infection 2020; 48:853–860.
Chen Y, Brook TC, Soe CZ, et al. Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors. Microb Genom 2020; 6:e000377.
Beaugerie L, Metz M, Barbut F, et al. Klebsiella oxytoca as an agent of antibiotic-associated hemorrhagic colitis. Clin Gastroenterol Hepatol 2003; 1:370–376.
Maharjan A, Bhetwal A, Shakya S, et al. Ugly bugs in healthy guts! Carriage of multidrug-resistant and ESBL-producing commensal Enterobacteriaceae in the intestine of healthy Nepalese adults. Infect Drug Resist 2018; 11:547–554.
Ohkusu K. Cost-effective and rapid presumptive identification of gram-negative bacilli in routine urine, pus, and stool cultures: evaluation of the use of CHROMagar orientation medium in conjunction with simple biochemical tests. J Clin Microbiol 2000; 38:4586–4592.
Glabonjat RA, Kitsera M, Unterhauser K, et al. Simultaneous quantification of enterotoxins tilimycin and tilivalline in biological matrices using HPLC high resolution ESMS(2) based on isotopically (15)N-labeled internal standards. Talanta 2021; 222:121677.
Herzog KA, Schneditz G, Leitner E, et al. Genotypes of Klebsiella oxytoca isolates from patients with nosocomial pneumonia are distinct from those of isolates from patients with antibiotic-associated hemorrhagic colitis. J Clin Microbiol 2014; 52:1607–1616.
Cosic A, Leitner E, Petternel C, et al. Variation in accessory genes within the Klebsiella oxytoca species complex delineates monophyletic members and simplifies coherent genotyping. Front Microbiol 2021; 12:692453.
Li JH, Oh J, Kienesberger S, et al. Making and breaking leupeptin protease inhibitors in pathogenic gammaproteobacteria. Angew Chem Int Ed Engl 2020; 59:17872–17880.
Gronlund MM, Lehtonen OP, Kero P, et al. Lactobacillus GG supplementation does not reduce faecal colonization of Klebsiella oxytoca in preterm infants. Acta Paediatr 1997; 86:785–786.
Baier C, Pirr S, Ziesing S, et al. Prospective surveillance of bacterial colonization and primary sepsis: findings of a tertiary neonatal intensive and intermediate care unit. J Hosp Infect 2019; 102:325–331.
Savino F, Cordisco L, Tarasco V, et al. Molecular identification of coliform bacteria from colicky breastfed infants. Acta Paediatr 2009; 98:1582–1588.
Stokholm J, Thorsen J, Chawes BL, et al. Cesarean section changes neonatal gut colonization. J Allergy Clin Immunol 2016; 138:881.e2–889.e2.
Voreades N, Kozil A, Weir TL. Diet and the development of the human intestinal microbiome. Front Microbiol 2014; 5:494.
Bergstrom A, Skov TH, Bahl MI, et al. Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol 2014; 80:2889–2900.
Backhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015; 17:690–703.
Vandenplas Y, Carnielli VP, Ksiazyk J, et al. Factors affecting early-life intestinal microbiota development. Nutrition 2020; 78:110812.
Zollner-Schwetz I, Hogenauer C, Joainig M, et al. Role of Klebsiella oxytoca in antibiotic-associated diarrhea. Clin Infect Dis 2008; 47:e74–e78.
Jensen MB, Olsen KE, Nielsen XC, et al. Diagnosis of Clostridium difficile : real-time PCR detection of toxin genes in faecal samples is more sensitive compared to toxigenic culture. Eur J Clin Microbiol Infect Dis 2015; 34:727–736.
Crobach MJ, Planche T, Eckert C, et al. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect 2016; 22: (Suppl 4): S63–S81.
Tse H, Gu Q, Sze KH, et al. A tricyclic pyrrolobenzodiazepine produced by Klebsiella oxytoca is associated with cytotoxicity in antibiotic-associated hemorrhagic colitis. J Biol Chem 2017; 292:19503–19520.
Alexander EM, Kreitler DF, Guidolin V, et al. Biosynthesis, mechanism of action, and inhibition of the enterotoxin tilimycin produced by the opportunistic pathogen Klebsiella oxytoca . ACS Infect Dis 2020; 6:1976–1997.
McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66:e1–e48.
Stapleton PJ, Murphy M, McCallion N, et al. Outbreaks of extended spectrum beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units: a systematic review. Arch Dis Child Fetal Neonatal Ed 2016; 101:F72–F78.