Current Clinical Microbiology Reports

, Volume 5, Issue 2, pp 97–105 | Cite as

Cronobacter spp.—Opportunistic Foodborne Pathogens: an Update on Evolution, Osmotic Adaptation and Pathogenesis

  • Angelika Lehner
  • Ben Davis Tall
  • Seamus Fanning
  • Shabarinath Srikumar
Foodborne Pathogens (S Johler, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Foodborne Pathogens


Purpose of Review

Cronobacter spp. are opportunistic, foodborne pathogens capable of causing severe illnesses predominantly in premature and low-birth-weight infants. These organisms have evolved features, which aid them to survive under harsh environmental conditions but may also contribute to pathogenesis during infection. In this review, we highlight efforts to study genetic diversity and evolutionary aspects, osmotic adaptation and pathogenesis of these pathogens.

Recent Findings

Next-generation genome sequencing-based techniques elucidated a species-level bidirectional divergence driven by niche adaptation in Cronobacter spp. Whole genome comparisons and proteomics revealed genes and pathways contributing to the survival and persistence phenotype in low-moisture environments. In silico genome comparisons and application of suitable in vivo models provided answers to pathogenesis-related questions.


Development and application of innovative molecular techniques and in vivo infection models have shed light on how Cronobacter spp. adapt to challenges experienced in natural, food processing and host-related environments.


Cronobacter spp. Evolution Osmotic adaptation Pathogenesis 


Compliance with Ethical Standards

Conflict of Interest

Dr. Lehner reports grants from Swiss National Science Foundation, during the conduct of the study.

Ben Davis Tall, Seamus Fanning and Shabarinath Srikumar declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards and international/national/institutional guidelines).


Recently published papers of particular interest have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Iversen C, Mullane N, McCardell B, Tall BD, Lehner A, Fanning S, et al. Cronobacter gen. nov., a new genus to accommodate the biogroups of Enterobacter sakazakii, and proposal of Cronobacter sakazakii gen. nov., comb. nov., Cronobacter malonaticus sp. nov., Cronobacter turicensis sp. nov., Cronobacter muytjensii sp. nov., Cronobacter dublinensis sp. nov., Cronobacter genomospecies 1, and of three subspecies, Cronobacter dublinensis subsp. dublinensis subsp. nov., Cronobacter dublinensis subsp. lausannensis subsp. nov. and Cronobacter dublinensis subsp. lactaridi subsp. nov. Int J Syst Evol Microbiol. 2008;58:1442–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Joseph S, Cetinkaya E, Drahovska H, Levican A, Figueras MJ, Forsythe SJ. Cronobacter condimenti sp. nov., isolated from spiced meat and Cronobacter universalis sp. nov., a novel species designation for Cronobacter sp. genomospecies 1, recovered from a leg infection, water, and food ingredients. Int J Syst Evol Microbiol. 2012;62:1277–83.CrossRefPubMedGoogle Scholar
  3. 3.
    Lai KK. Enterobacter sakazakii infections among neonates, infants, children, and adults. Case reports and a review of the literature. Medicine (Baltimore). 2001;80:113–22.CrossRefGoogle Scholar
  4. 4.
    Stoll BJ, Hansen N, Fanaroff AA, Lemons JA. Enterobacter sakazakii is a rare cause of neonatal septicemia or meningitis in VLBW infants. J Pediatr. 2004;144:821–3.PubMedGoogle Scholar
  5. 5.
    Cruz-Cordova A, Rocha-Ramırez LM, Ochoa SA, Gonzalez-Pedrajo B, Espinosa N, et al. Flagella from five Cronobacter species induce pro-inflammatory cytokines in macrophage derivatives from human monocytes. PLoS One. 2012;7:e52091.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Healy B, Cooney S, O’Brien S, Iversen C, Whyte P, Nally J, et al. Cronobacter (Enterobacter sakazakii): an opportunistic foodborne pathogen. Foodborne Pathog Dis. 2010;7:339–50.CrossRefPubMedGoogle Scholar
  7. 7.
    Food and Agriculture Organization of the United Nations/ World Health Organization (FAO/WHO), Enterobacter sakazakii (Cronobacter spp.) in powdered follow-up formulae. 2008 Microbiological Risk Assessment Series 15. Rome.Google Scholar
  8. 8.
    Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO), Enterobacter sakazakii and Salmonella in powdered infant formula (Meeting Report). 2006 Microbiological Risk AssessmentSeries 10. Rome.Google Scholar
  9. 9.
    Bowen AB, Braden CR. Invasive Enterobacter sakazakii disease in infants. Emerg Infect Dis. 2006;12:1185–9.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Friedemann M. Enterobacter sakazakii in food and beverages (other than infant formula and milk powder). Int J Food Microbiol. 2007;116:1–10.CrossRefPubMedGoogle Scholar
  11. 11.
    Schmid M, Iversen C, Gontia I, Stephan R, Hofmann A, Jha B, et al. Evidence for a plant-associated natural habitat for Cronobacter spp. Res Microbiol. 2009;160:608–14.CrossRefPubMedGoogle Scholar
  12. 12.
    Hochel I, Ruzickova H, Krasny L, Demnerova K. Occurrence of Cronobacter spp. in retail foods. J Appl Microbiol. 2012;112:1257–65.CrossRefPubMedGoogle Scholar
  13. 13.
    Himelright I, Harris E, Lorch V, Anderson M, Jones T, Craig A, et al. Enterobacter sakazakii infections associated with the use of powdered infant formula—Tennessee, 2001. MMWR Morb Mortal Wkly Rep. 2002;51:297–300.Google Scholar
  14. 14.
    Hunter CJ, Bean JF. Cronobacter: an emerging opportunistic pathogen associated with neonatal meningitis, sepsis and necrotizing enterocolitis. J Perinatol. 2013;33:581–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Jaradat ZW, Al Mousa W, Elbetieha A, Al Nabulsi A, Tall BT. Cronobacter spp.—opportunistic food-borne pathogens. A review of their virulence and environmental-adaptive traits. J Med Microbiol. 2014;63:1023–37.CrossRefPubMedGoogle Scholar
  16. 16.
    Seo KH, Brackett RE. Rapid, specific detection of Enterobacter sakazakii in infant formula using a real-time PCR assay. J Food Prot. 2005;68:59–63.CrossRefPubMedGoogle Scholar
  17. 17.
    Lehner A, Nitzsche S, Breeuwer P, Diep B, Thelen K, Stephan R. Comparison of two chromogenic media and evaluation of two molecular based identification systems for Enterobacter sakazakii detection. BMC Microbiol. 2006;6:15.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Stoop B, Lehner A, Iversen C, Fanning S, Stephan R. Development and evaluation of rpoB based PCR systems to differentiate the six proposed species within the genus Cronobacter. Int J Food Microbiol. 2009;136:165–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Lehner A, Fricker Feer C, Stephan R. Identification of the recently described Cronobacter condimenti by an rpoB-gene-based PCR system. J Med Microbiol. 2012;61:1034–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Jarvis KG, Grim CJ, Franco AA, Gopinath G, Sathyarmoorthy V, Hu L, et al. Molecular caracterization of Cronobacter lipopolysaccharide O-antigen gene clusters and development of serotype-specific PCR assays. Appl Environ Microbiol. 2011;77:4017–26.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sun Y, Wang M, Wang Q, Cao B, He X, Li K, et al. Genetic analysis of the Cronobacter sakazakii O4 to O7 O-antigen gene clusters and development of a PCR assay for identification of all C. sakazakii serotypes. Appl Environ Microbiol. 2012;78:3966–74.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Yan Q, Fanning S. Pulsed-field gel electrophoresis (PFGE) for pathogenic Cronobacter species. Methods Mol Biol. 2015;1301:55–69.CrossRefPubMedGoogle Scholar
  23. 23.
    Mueller A, Stephan R, Fricker-Feer C, Lehner A. Genetic diversity of Cronobacter sakazakii isolates collected from a Swiss infant formula production facility. J Food Prot. 2013;76:883–7.CrossRefGoogle Scholar
  24. 24.
    Stoller A, Stephan R, Fricker-Feer C, Lehner A. Epidemiological investigation of a powdered infant formula product batch contaminated with Cronobacter in a Swiss infant formula production facility. Austin Food Sci. 2016;1:1028.Google Scholar
  25. 25.
    Baldwin A, Loughlin M, Caubilla-Barron J, Kucerova E, Manning G, Dawson C, et al. Multilocus sequence typing of Cronobacter sakazakii and Cronobacter malonaticus reveals stable clonal structures with clinical significance which do not correlate with biotypes. BMC Microbiol. 2009;9:223.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Joseph S, Forsythe SJ. Insights into the emergent bacterial pathogen Cronobacter spp., generated by multilocus seqeunce typing and analysis. Front Microbiol. 2012;3:397.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Joseph S, Sonbol H, Hariri S, Desai P, McClelland M, Forsythe SJ. Diversity of the Cronobacter genus as revealed by multilocus sequence typing. J Clin Microbiol. 2012;50:3031–9.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Yan Q, Wang J, Gangiredla J, Cao Y, Martins M, Gopinath GR, et al. Comparative genotypic and phenotypic analysis of Cronobacter species cultured from four powdered infant formula production facilities: indication of pathoadaptation along the food chain. Appl Environ Microbiol. 2015;81:4388–402.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Joseph S, Forsythe SJ. Predominance of Cronobacter sakazakii sequence type 4 in neonatal infections. Emerg Infect Dis. 2011;7:1713–5.CrossRefGoogle Scholar
  30. 30.
    Hariri S, Joseph S, Forsythe SJ. Predominance of Cronobacter sakazakii ST4 strains in Cronobacter neonatal meningitis United States. Emerg Infect Dis. 2013;19:175–7.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Mramba F, Broce A, Zurek L. Isolation of Enterobacter sakazakii from stable flies, Stomoxys calcitrans L. (Diptera: Muscidae). J Food Prot. 2006;69:671–3.CrossRefPubMedGoogle Scholar
  32. 32.
    Pava-Ripoll M, Pearson REG, Miller AK, Ziobro GC. Prevalence and relative risk of Cronobacter spp., Salmonella spp., and Listeria monocytogenes associated with the body surfaces and guts of individual filth flies. App Environ Microbiol. 2012;78:7891–902.CrossRefGoogle Scholar
  33. 33.
    Forsythe SJ, Dickins B, Jolley KA. Cronobacter, the emergent bacterial pathogen Enterobacter sakazakii comes of age; MLST and whole genome sequence analysis. BMC Genomics. 2014;15:1121.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kucerova E, Clifton SW, Xia XQ, Long F, Porwolnik S, Fulton L, et al. Genome sequence of Cronobacter sakazakii BAA-894 and comparative genomic hybridization analysis with other Cronobacter species. PLoS One. 2010;5:e9556.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Grim CJ, Kotewicz ML, Power KA, Gopinath G, Franco AA, Jarvis KG, et al. Pan-genome analysis of the emerging foodborne pathogen Cronobacter spp. suggests a species-level bidirectional divergence driven by niche adaptation. BMC Genomics. 2013;14:366.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Franco AA, Hu L, Grim CJ, Gopinath G, Sathyamoorthy V, Jarvis KG, et al. Characterization of putative virulence genes on the related RepFIB plasmids harbored by Cronobacter spp. Appl Environ Microbiol. 2011;77:3255–67.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    • Eshwar AK, Tall BD, Gangiredla J, Gopinath GR, Patel IR, Neuhauss SCF, et al. Linking genomo- and pathotype: exploiting the zebrafish embryo model to investigate the divergent virulence potential among Cronobacter spp. PLoS One. 2016;11:e0158428. In this study, the potential of the zebrafish embryo model to study pathogenesis in Cronobacter spp. is discussed.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Chase HR, Gopinath GR, Eshwar AK, Stoller A, Fricker-Feer C, Gangiredla J, et al. Comparative genomic characterization of the highly persistent and potentially virulent Cronobacter sakazakii ST83, CC65 strain H322 and other ST83 strains. Front Microbiol. 2017;8:1136.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Tall BD, Gangiredla J, Gopinath GR, Yan Q, Chase HR, Lee B, et al. Development of a custom-designed, pan genomic DNA microarray to characterize strain-level diversity among Cronobacter spp. Front Pediatr. 2015;3:36.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    • Tall BD, Gangiredla J, Grim CJ, Patel IR, Jackson SA, Mammel MK, et al. Use of a pan-genomic DNA microarray in determination of the phylogenetic relatedness among Cronobacter spp. and its use as a data mining tool to understand Cronobacter biology. Microarrays. 2017;4:6. This study demonstates the application possibilities of the Cronobacter microarray.CrossRefGoogle Scholar
  41. 41.
    Yan Q, Power KA, Cooney S, Fox E, Gopinath GR, et al. Complete genome sequence and phenotype microarray analysis of Cronobacter sakazakii SP291: a persistent isolate cultured from a powdered infant formula production facility. Front Microbiol. 2013;4:256.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Gurtler JB, Beuchat LR. Survival of Enterobacter sakazakii in powdered infant formula as affected by composition, water activity, and temperature. J Food Prot. 2007;70:1579–86.CrossRefPubMedGoogle Scholar
  43. 43.
    Beuchat LR, Komitopoulou E, Beckers H, Betts RP, Bourdichon F, et al. Low water activity foods: increased concern as vehicles of foodborne pathogens. J Food Prot. 2013;76:150–72.CrossRefPubMedGoogle Scholar
  44. 44.
    Podolak R, Enache E, Stone W, Black DG, Elliott PH. Sources and risk factors for contamination, survival, persistence, and heat resistance of Salmonella in low-moisture foods. J Food Prot. 2010;73:1919–36.CrossRefPubMedGoogle Scholar
  45. 45.
    Breeuwer P, Lardeau A, Peterz M, Joosten HM. Desiccation and heat tolerance of Enterobacter sakazakii. J Appl Microbiol. 2003;95:967–73.CrossRefPubMedGoogle Scholar
  46. 46.
    Barron JC, Forsythe SJ. Dry stress and survival time of Enterobacter sakazakii and other Enterobacteriaceae in dehydrated powdered infant formula. J Food Prot. 2007;70:2111–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Drudy D, O’Rourke M, Murphy M, Mullane NR, O’Mahony R, Kelly L, et al. Characterization of a collection of Enterobacter sakazakii isolates from environmental and food sources. Int J Food Microbiol. 2006;110:127–34.CrossRefPubMedGoogle Scholar
  48. 48.
    Mullane NR, Ryan M, Iversen C, Murphy M, O’Gaora P, Quinn T, et al. Development of multiple-locus variable-number tandem-repeat analysis for the molecular subtyping of Enterobacter sakazakii. Appl Environ Microbiol. 2008;74:1223–31.CrossRefPubMedGoogle Scholar
  49. 49.
    Mullane NR, Whyte P, Wall PG, Quinn T, Fanning S. Application of pulsed-field gel electrophoresis to characterise and trace the prevalence of Enterobacter sakazakii in an infant formula processing facility. Int J Food Microbiol. 2007;116:73–81.CrossRefPubMedGoogle Scholar
  50. 50.
    Feeney A, Sleator RD. An in silico analysis of osmotolerance in the emerging gastrointestinal pathogen Cronobacter sakazakii. Bioeng Bugs. 2011;2:260–70.CrossRefPubMedGoogle Scholar
  51. 51.
    Power KA, Yan Q, Fox EM, Cooney S, Fanning S. Genome sequence of Cronobacter sakazakii SP291, a persistent thermotolerant isolate derived from a factory producing powdered infant formula. Genome Announc. 2013;1:e0008213.CrossRefPubMedGoogle Scholar
  52. 52.
    Riedel K, Lehner A. Identification of proteins involved in osmotic stress response in Enterobacter sakazakii by proteomics. Proteomics. 2007;7:1217–31.CrossRefPubMedGoogle Scholar
  53. 53.
    •• Hu S, Yu Y, Wu X, Xia X, Xiao X, Wu H. Comparative proteomic analysis of Cronobacter sakazakii by iTRAQ provides insights into response to desiccation. Food Res Int. 2017;100:631–9. In this study, the most actual information on Cronobacter desiccation stress response is given.CrossRefPubMedGoogle Scholar
  54. 54.
    Cayley S, Lewis BA, Guttman HJ, Record MT Jr. Characterization of the cytoplasm of Escherichia coli K-12 as a function of external osmolarity. Implications for protein-DNA interactions in vivo. J Mol Biol. 1991;222:281–300.CrossRefPubMedGoogle Scholar
  55. 55.
    Dosch DC, Helmer GL, Sutton SH, Salvacion FF, Epstein W. Genetic analysis of potassium transport loci in Escherichia coli: evidence for three constitutive systems mediating uptake potassium. J Bacteriol. 1991;173:687–96.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Sleator RD, Wouters J, Gahan CG, Abee T, Hill C. Analysis of the role of OpuC, an osmolyte transport system, in salt tolerance and virulence potential of Listeria monocytogenes. Appl Environ Microbiol. 2001;67:2692–8.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Nakamura T, Yamamuro N, Stumpe S, Unemoto T, Bakker EP. Cloning of the trkAH gene cluster and characterization of the Trk K(+)-uptake system of Vibrio alginolyticus. Microbiology. 1998;144:2281–9.CrossRefPubMedGoogle Scholar
  58. 58.
    Roe AJ, McLaggan D, O’Byrne CP, Booth IR. Rapid inactivation of the Escherichia coli Kdp K+ uptake system by high potassium concentrations. Mol Microbiol. 2000;35:1235–43.CrossRefPubMedGoogle Scholar
  59. 59.
    Gralla JD, Vargas DR. Potassium glutamate as a transcriptional inhibitor during bacterial osmoregulation. EMBO J. 2006;25:1515–21.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Dinnbier U, Limpinsel E, Schmid R, Bakker EP. Transient accumulation of potassium glutamate and its replacement by trehalose during adaptation of growing cells of Escherichia coli K-12 to elevated sodium chloride concentrations. Arch Microbiol. 1988;150:348–57.CrossRefPubMedGoogle Scholar
  61. 61.
    Wood JM. Proline porters effect the utilization of proline as nutrient or osmoprotectant for bacteria. J Membr Biol. 1988;106:183–202.CrossRefPubMedGoogle Scholar
  62. 62.
    Finn S, Handler K, Condell O, Colgan A, Cooney S, McClure P, et al. ProP is required for the survival of desiccated Salmonella enterica serovar Typhimurium cells on a stainless steel surface. Appl Environ Microbiol. 2013;79:4376–84.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Sola-Penna M, Meyer-Fernandes JR. Stabilization against thermal inactivation promoted by sugars on enzyme structure and function: why is trehalose more effective than other sugars? Arch Biochem Biophys. 1998;360:10–4.CrossRefPubMedGoogle Scholar
  64. 64.
    Purvis JE, Yomano LP, Ingram LO. Enhanced trehalose production improves growth of Escherichia coli under osmotic stress. Appl Environ Microbiol. 2005;71:3761–9.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Hunter CJ, Williams M, Petrosyan M, Guner Y, Mittal R, Mock D, et al. Lactobacillus bulgaricus prevents intestinal epithelial cell injury caused by Enterobacter sakazakii-induced nitric oxide both in vitro and in the newborn rat model of necrotizing enterocolitis. Infect Immun. 2009;77:1031–43.CrossRefPubMedGoogle Scholar
  66. 66.
    Liu Q, Mittal R, Emami CN, Iversen C, Ford HR, Prasadarao NV. Human isolates of Cronobacter sakazakii bind efficiently to intestinal epithelial cells in vitro to induce monolayer permeability and apoptosis. J Surg Res. 2012;176:437–47.CrossRefPubMedGoogle Scholar
  67. 67.
    Grishin A, Papillon S, Bell B, Wang J, Ford H. The role of the intestinal microbiota in the pathogenesis of necrotizing enterocolitis. Semin Pediatr Surg. 2013;22:69–75.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Mange JP, Stephan R, Borel N, Wild P, Kim KS, Pospischil A, et al. Adhesive properties of Enterobacter sakazakii to human epithelial and brain microvascular endothelial cells. BMC Microbiol. 2006;6:58.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Kim KP, Loessner MJ. Enterobacter sakazakii invasion in human intestinal Caco-2 cells requires the host cell cytoskeleton and is enhanced by disruption of tight junction. Infect Immun. 2008;76:562–70.CrossRefPubMedGoogle Scholar
  70. 70.
    Nair MK, Venkitanarayanan K. Role of bacterial OmpA and host cytoskeleton in the invasion of human intestinal epithelial cells by Enterobacter sakazakii. Pediatr Res. 2007;62:664–9.CrossRefGoogle Scholar
  71. 71.
    Mittal R, Wang Y, Hunter CJ, Gonzalez-Gomez I, Prasadarao NV. Brain damage in newborn rat model of meningitis by Enterobacter sakazakii: a role for outer membrane protein A. Lab Investig. 2009;89:263–77.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Mittal R, Bulgheresi S, Emami C, Prasadarao NV. Enterobacter sakazakii targets DC-SIGN to induce immunosuppressive responses in cultured human intestinal epithelial cells and human brain microvascular endothelial cells. Microb Pathog. 2009;52:140–7.Google Scholar
  73. 73.
    Nair MK, Venkitanarayanan K, Silbart LK, Kim KS. Outer membrane protein A (OmpA) of Cronobacter sakazakii binds fibronectin and contributes to invasion of human brain microvascular endothelial cells. Foodborne Pathog Dis. 2009;6:495–501.CrossRefPubMedGoogle Scholar
  74. 74.
    Giri CP, Shima K, Tall BD, Curtis S, Sathyamoorthy V, Hanisch B, et al. Cronobacter spp.(previously Enterobacter sakazakii) invade and translocate across both cultured human intestinal epithelial cells and human brain microvascular endothelial cells. Microb Pathog. 2012;52:140–7.CrossRefPubMedGoogle Scholar
  75. 75.
    Kim K, Kim KP, Choi J, Lim JA, Lee J, Hwang H, et al. Outer membrane proteins A (OmpA) and X (OmpX) are essential for basolateral invasion of Cronobacter sakazakii. Appl Environ Microbiol. 2010;76:5188–98.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Emami CN, Mittal R, Wang L, Ford HR, Prasadarao NV. Recruitment of dendritic cells is responsible for intestinal epithelial damage in the pathogenesis of necrotizing enterocolitis by Cronobacter sakazakii. J Immunol. 2011;186:7067–79.CrossRefPubMedGoogle Scholar
  77. 77.
    Emami CN, Mittal R, Wang L, Ford HR, Prasadarao NV. Role of neutrophils and macrophages in the pathogenesis of necrotizing enterocolitis caused by Cronobacter sakazakii. J Surg Res. 2012;172:18–28.CrossRefPubMedGoogle Scholar
  78. 78.
    Hunter CJ, Singamsetty VK, Chokshi NK, Boyle P, Camerini V, Grishin AV, et al. Enterobacter sakazakii enhances epithelial cell injury by inducing apoptosis in a rat model of necrotizing enterocolitis. J Infect Dis. 2008;198:586–93.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Moriez R, Salvador-Cartier C, Theodorou V, Fioramonti J, Eutamene H, Bueno L. Myosin light chain kinase is involved in lipopolysaccharide-induced disruption of colonic epithelial barrier and bacterial translocation in rats. Am J Pathol. 2005;167:1071–9.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Townsend S, Caubilla Barron J, Loc-Carrillo C, Forsythe S. The presence of endotoxin in powdered infant formula milk and the influence of endotoxin and Enterobacter sakazakii on bacterial translocation in the infant rat. Food Microbiol. 2007;24:67–74.CrossRefPubMedGoogle Scholar
  81. 81.
    Townsend SM, Hurrell E, Gonzalez-Gomez I, Lowe J, Frye JG, Forsythe S, et al. Enterobacter sakazakii invades brain capillary endothelial cells, persists in human macrophages influencing cytokine secretion and induces severe brain pathology in the neonatal rat. Microbiology. 2007;153:3538–47.CrossRefPubMedGoogle Scholar
  82. 82.
    Townsend S, Hurrell E, Forsythe S. Virulence studies of Enterobacter sakazakii isolates associated with a neonatal intensive care unit outbreak. BMC Microbiol. 2008;8:64.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Eshwar AK, Tasara T, Stephan R, Lehner A. Influence of FkpA variants on survival and replication of Cronobacter spp. in human macrophages. Res Microbiol. 2015;166:186–95.CrossRefPubMedGoogle Scholar
  84. 84.
    Schwizer S, Tasara T, Zurfluh K, Stephan R, Lehner A. Identification of genes involved in serum tolerance in the clinical strain Cronobacter sakazakii ES5. BMC Microbiol. 2013;13:38.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Franco AA, Kothary MH, Gopinath G, Jarvis KG, Grim CJ, Hu L, et al. Cpa, the outer membrane protease of Cronobacter sakazakii, activates plasminogen and mediates resistance to serum bactericidal activity. Infect Immun. 2011;79:1578–87.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Yan QQ, Condell O, Power K, Butler F, Tall BD, Fanning S. Cronobacter species (formerly known as Enterobacter sakazakii) in powdered infant formula: a review of our current understanding of the biology of this bacterium. J Appl Microbiol. 2012;113:1–15.CrossRefPubMedGoogle Scholar
  87. 87.
    Singamsetty VK, Wang Y, Shimada H, Prasadarao NV. Outer membrane protein A expression in Enterobacter sakazakii is required to induce microtubule condensation in human brain microvascular endothelial cells for invasion. Microb Pathog. 2008;45:181–91.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Liu DX, Zhao WD, Fang WG, Chen YH. cPLA2a mediated actin rearrangements downstream of the Akt signaling is required for Cronobacter sakazakii invasion into brain endothelial cells. Biochem Biophys Res Commun. 2012;417:925–30.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Angelika Lehner
    • 1
  • Ben Davis Tall
    • 2
  • Seamus Fanning
    • 3
  • Shabarinath Srikumar
    • 3
  1. 1.Institute for Food Safety and HygieneUniversity of ZurichZürichSwitzerland
  2. 2.CFSANFDALaurelUSA
  3. 3.UCD-Centre for Food Safety, Science Centre SouthUniversity College DublinDublinIreland

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