Skip to main content

Virulence Traits in the Cronobacter Genus

  • Chapter
  • First Online:
Foodborne Pathogens

Part of the book series: Food Microbiology and Food Safety ((PRACT))

  • 1724 Accesses

Abstract

Members of the Cronobacter genus are opportunistic pathogens within the bacterial family Enterobacteriaceae. They are associated with rare and sporadic infections in adults and associated with severe life threatening outbreaks of necrotizing enterocolitis, as well as causing meningitis and sepsis in neonates and infants. The organism is most commonly known for its infections of highly susceptible neonates through the consumption of contaminated reconstituted powdered infant formula; however, most infections are in the adult population and, therefore, wider sources of exposure and mechanisms of infection need to be better elucidated. This chapter will review the array of Cronobacter’s virulence traits, which may aid the organisms’ pathogenicity. In addition, environmental fitness will also be considered, as this may be crucial to understanding the prevalence of Cronobacter pathovars with particular infections in specific age groups.

Cronobacter has an array of virulence factors that facilitate tissue adhesion, invasion, and host cell injury. The outer membrane protein A (OmpA), is one such virulence marker, which also has importance in neonatal meningitic E. coli pathogenesis. Various plasmid-associated genes, such as those for filamentous hemagglutinin (fhaBC), Cronobacter plasminogen activator (cpa), as well as chromosomal genes responsible for iron acquisition (eitCBAD) and iucABD/iutA) and sialic acid utilization (nanAKT) have been reported. The possession of these virulence factors alone does not necessarily define a Cronobacter strain as being virulent, as there is also the aspect of environmental fitness. Physiological properties, such as biofilm formation and resistance to desiccation, may also contribute to the incidence of infection, as they increase its persistence in the environment and, hence, increase exposure. Capsular profiling has revealed an association between strains producing specific K-antigen, colanic acid and cellulose with neonatal meningitis, which could be linked to both host immune evasion as well as environmental survival. Recently, the use of whole genome comparative analysis with >200 strains has revealed the variation in the prevalence of virulence traits across the genus. In parallel is the recent recognition of specific pathovars, being linked to clonal lineages; for example, C. sakazakii CC4 with neonatal meningitis. These associations should lead to future virulence studies with well-chosen genetically characterized strains.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

CC:

Clonal complex

CDC:

U.S. Centers for Disease Control and Prevention

CNS:

Central nervous system

FAO-WHO:

Food and Agriculture Organization of the United Nations-World Health Organization

ICMSF:

International Commission on Microbiological Specifications for Foods

MLSA:

Multilocus sequence analysis

MLST:

Multilocus sequence typing

NEC:

Necrotizing enterocolitis

NICU:

Neonatal intensive care units

PFGE:

Pulsed-field gel electrophoresis

PIF:

Powdered infant formula

ST:

Sequence type

UTI:

Urinary tract infection

WHO:

World Health Organization

References

  • Aktan, F. (2004). iNOS-mediated nitric oxide production and its regulation. Life Sciences, 75, 639–653.

    Article  CAS  PubMed  Google Scholar 

  • Almajed, F. S., & Forsythe, S. J. (2016). Cronobacter sakazakii clinical isolates overcome host barriers and evade the immune response. Microbial Pathogenesis, 90, 55–63.

    Article  CAS  PubMed  Google Scholar 

  • Alsonosi, A., Hariri, S., KajsĂ­k, M., Oriešková, M., HanulĂ­k, V., Röderová, M., PetrĹľelová, J., Kollárová, H., Drahovská, H., & Forsythe, S. (2015). The speciation and genotyping of Cronobacter isolates from hospitalised patients. European Journal of Clinical Microbiology & Infectious Diseases, 34, 1979–1988.

    Article  CAS  Google Scholar 

  • Alzahrani, H., Winter, J., Boocock, D., De Girolamo, L., & Forsythe, S. J. (2015). Characterisation of outer membrane vesicles from a neonatal meningitic strain of Cronobacter sakazakii. FEMS Microbiology Letters, 362, fnv085.

    Article  PubMed  Google Scholar 

  • Baldwin, A., Loughlin, M., Caubilla-Barron, J., Kucerova, E., Manning, G., Dowson, C., & Forsythe, S. (2009). Multilocus sequence typing of Cronobacter sakazakii and Cronobacter malonaticus reveals stable clonal structures with clinical significance which do not correlate with biotypes. BMC Microbiology, 9, 223–231.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ballabh, P., Braun, A., & Nedergaard, M. (2004). The blood–brain barrier: An overview: Structure, regulation, and clinical implications. Neurobiology of Disease, 16, 1–13.

    Article  CAS  PubMed  Google Scholar 

  • Bar-Oz, B., Preminger, A., Peleg, O., Block, C., & Arad, I. (2001). Enterobacter sakazakii infection in the newborn. Acta Paediatrica, 90, 356–358.

    Article  CAS  PubMed  Google Scholar 

  • Barichello, T., Fagundes, G. D., Generoso, J. S., Elias, S. G., Simões, L. R., & Teixeira, A. L. (2013). Pathophysiology of neonatal acute bacterial meningitis. Journal of Medical Microbiology, 62, 1781–1789.

    Article  CAS  PubMed  Google Scholar 

  • Barron, K. D. (1995). The microglial cell a historical review. Journal of the Neurological Sciences, 134, 57–68.

    Article  PubMed  Google Scholar 

  • Beaman, L., & Beaman, B. L. (1984). The role of oxygen and its derivatives in microbial pathogenesis and host defense. Annual Reviews in Microbiology, 38, 27–48.

    Google Scholar 

  • Bell, M. J., Ternberg, J. L., Feigin, R. D., Keating, J. P., Marshall, R., Barton, L., & Brotherton, T. (1978). Neonatal necrotizing enterocolitis therapeutic decisions based upon clinical staging. Annals of Surgery, 187, 1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biering, G., Karlsson, S., Clark, N. C., JĂłnsdĂłttir, K. E., Ludvigsson, P., & Steingrimsson, O. (1989). Three cases of neonatal meningitis caused by Enterobacter sakazakii in powdered milk. Journal of Clinical Microbiology, 27, 2054–2056.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Birgegard, G., & Caro, J. (1984). Increased ferritin synthesis and iron uptake in inflammatory mouse macrophages. Scandinavian Journal of Haematology, 33, 43–48.

    Article  CAS  PubMed  Google Scholar 

  • Bishop, G. M., Dang, T. N., Dringen, R., & Robinson, S. R. (2011). Accumulation of non-transferrin-bound iron by neurons, astrocytes, and microglia. Neurotoxicity Research, 19, 443–451.

    Article  CAS  PubMed  Google Scholar 

  • Bogard, R. W., & Oliver, J. D. (2007). Role of iron in human serum resistance of the clinical and environmental Vibrio vulnificus genotypes. Applied and Environmental Microbiology, 73, 7501–7505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bowen, A. B., & Braden, C. R. (2006). Invasive Enterobacter sakazakii disease in infants. Emerging Infectious Diseases, 12, 1185.

    Article  PubMed  PubMed Central  Google Scholar 

  • Broge, T., & Lee, A. (2013). A case of Cronobacter (Enterobacter sakazakii) bacteremia in a breastfed infant. Journal of the Pediatric Infectious Diseases Society, 2, e1–e2.

    Article  PubMed  Google Scholar 

  • Caubilla-Barron, J., Hurrell, E., Townsend, S., Cheetham, P., Loc-Carrillo, C., Fayet, O., Prere, M. F., & Forsythe, S. (2007). Genotypic and phenotypic analysis of Enterobacter sakazakii strains from an outbreak resulting in fatalities in a neonatal intensive care unit in France. Journal of Clinical Microbiology, 45, 3979–3985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • CDC. (2009). Cronobacter species isolation in two infants-New Mexico, 2008. MMWR. Morbidity and Mortality Weekly Report, 58, 1179.

    Google Scholar 

  • Cetin, S., Ford, H. R., Sysko, L. R., Agarwal, C., Wang, J., Neal, M. D., Baty, C., Apodaca, G., & Hackam, D. J. (2004). Endotoxin inhibits intestinal epithelial restitution through activation of rho-GTPase and increased focal adhesions. Journal of Biological Chemistry, 279, 24592–24600.

    Article  CAS  PubMed  Google Scholar 

  • Choi, Y., Kim, S., Hwang, H., Kim, K. P., Kang, D. H., & Ryu, S. (2015). Plasmid-encoded MCP is involved in virulence, motility, and biofilm formation of Cronobacter sakazakii ATCC 29544T. Infection and Immunity, 83, 197–204.

    Article  PubMed  CAS  Google Scholar 

  • Cohen, J. J., Duke, R. C., Fadok, V. A., & Sellins, K. S. (1992). Apoptosis and programmed cell death in immunity. Annual Review of Immunology, 10, 267–293.

    Article  CAS  PubMed  Google Scholar 

  • Cruz, A., Xicohtencatl-Cortes, J., González-Pedrajo, B., Bobadilla, M., Eslava, C., & Rosas, I. (2011). Virulence traits in Cronobacter species isolated from different sources. Canadian Journal of Microbiology, 57, 735–744.

    Article  CAS  PubMed  Google Scholar 

  • Cruz-CĂłrdova, A., Rocha-RamĂ­rez, L. M., Ochoa, S. A., GĂłnzalez-Pedrajo, B., Espinosa, N., Eslava, C., Hernández-Chiñas, U., Mendoza-Hernández, G., RodrĂ­guez-Leviz, A., Valencia-Mayoral, P., Sadowinski-Pine, S., Hernández-Castro, R., Estrada-GarcĂ­a, I., Muñoz-Hernández, O., Rosas, I., & Xicohtencatl-Cortes, J. (2012). Flagella from five Cronobacter species induce pro-inflammatory cytokines in macrophage derivatives from human monocytes. PloS One, 7, e52091.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dimmeler, S., & Zeiher, A. M. (1997). Nitric oxide and apoptosis: Another paradigm for the double-edged role of nitric oxide. Nitric Oxide: Biology and Chemistry, 1, 275–281.

    Article  CAS  Google Scholar 

  • Emami, C. N., Mittal, R., Wang, L., Ford, H. R., & Prasadarao, N. V. (2011). Recruitment of dendritic cells is responsible for intestinal epithelial damage in the pathogenesis of necrotizing enterocolitis by Cronobacter sakazakii. The Journal of Immunology, 186, 7067–7079.

    Article  CAS  PubMed  Google Scholar 

  • Emami, C. N., Mittal, R., Wang, L., Ford, H. R., & Prasadarao, N. V. (2012). Role of neutrophils and macrophages in the pathogenesis of necrotizing enterocolitis caused by Cronobacter sakazakii. Journal of Surgical Research, 172, 18–28.

    Article  CAS  PubMed  Google Scholar 

  • Farmer, J. J., Asbury, M., Hickman, F., & Brenner, D. O. N. J. (1980). Enterobacter sakazakii: A new species of “Enterobacteriaceae” isolated from clinical specimens. International Journal of Systematic Bacteriology, 30, 569–584.

    Article  Google Scholar 

  • FAO-WHO (Food and Agricultural Organization-World Health Organization). (2006). Enterobacter sakazakii and Salmonella In Powdered Infant Formula. In Microbiological risk assessment series 10. Rome. http://www.who.int/foodsafety/publications/mra10/en/

  • Flores, J. P., Medrano, S. A., Sánchez, J. S., & Fernandez-Escartin, E. (2011). Two cases of hemorrhagic diarrhea caused by Cronobacter sakazakii in hospitalized nursing infants associated with the consumption of powdered infant formula. Journal of Food Protection, 74, 2177–2181.

    Article  PubMed  Google Scholar 

  • Forsythe, S. J. (2005). Enterobacter sakazakii and other bacteria in powdered infant milk formula. Maternal & Child Nutrition, 1, 44–50.

    Article  Google Scholar 

  • Forsythe, S. J., Dickins, B., & Jolley, K. A. (2014). Cronobacter, the emergent bacterial pathogen Enterobacter sakazakii comes of age; MLST and whole genome sequence analysis. BMC Genomics, 15, 1121.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Franco, A., Hu, L., Grim, C., Gopinath, G., Sathyamoorthy, V., Jarvis, K., Lee, C., Sadowski, J., Kim, J., & Kothary, M. (2011a). Characterization of putative virulence genes on the related RepFIB plasmids harbored by Cronobacter spp. Applied and Environmental Microbiology, 77, 3255–3267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franco, A., Kothary, M., Gopinath, G., Jarvis, K., Grim, C., Hu, L., Datta, A., McCardell, B., & Tall, B. (2011b). Cpa, the outer membrane protease of Cronobacter sakazakii, activates plasminogen and mediates resistance to serum bactericidal activity. Infection and Immunity, 79, 1578–1587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friedemann, M. (2007). Enterobacter sakazakii in food and beverages (other than infant formula and milk powder). International Journal of Food Microbiology, 116, 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Friedemann, M. (2009). Epidemiology of invasive neonatal Cronobacter (Enterobacter sakazakii) infections. European Journal of Clinical Microbiology & Infectious Diseases, 28, 1297–1304.

    Article  CAS  Google Scholar 

  • Giri, C. P., Shima, K., Tall, B. D., Curtis, S., Sathyamoorthy, V., Hanisch, B., Kim, K. S., & Kopecko, D. J. (2011). Cronobacter spp. (previously Enterobacter sakazakii) invade and translocate across both cultured human intestinal epithelial cells and human brain microvascular endothelial cells. Microbial Pathogenesis, 52, 140–147.

    Article  PubMed  CAS  Google Scholar 

  • Grim, C., Kothary, M., Gopinath, G., Jarvis, K., Beaubrun, J. J.-G., McClelland, M., Tall, B., & Franco, A. (2012). Identification and characterization of Cronobacter iron acquisition systems. Applied and Environmental Microbiology, 78, 6035–6050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grim, C. J., Kotewicz, M. L., Power, K. A., Gopinath, G., Franco, A. A., Jarvis, K. G., Yan, Q. Q., Jackson, S. A., Sathyamoorthy, V., & Hu, L. (2013). Pan-genome analysis of the emerging foodborne pathogen Cronobacter spp. suggests a species-level bidirectional divergence driven by niche adaptation. BMC Genomics, 14, 366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gross, S. S., & Wolin, M. (1995). Nitric oxide: Pathophysiological mechanisms. Annual Review of Physiology, 57, 737–769.

    Article  CAS  PubMed  Google Scholar 

  • Hariri, S., Joseph, S., & Forsythe, S. J. (2013). Cronobacter sakazakii ST4 strains and neonatal meningitis, United States. Emerging Infectious Diseases, 19, 175.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hartmann, I., Carranza, P., Lehner, A., Stephan, R., Eberl, L., & Riedel, K. (2010). Genes involved in Cronobacter sakazakii biofilm formation. Applied and Environmental Microbiology, 76, 2251–2261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henry, M. C. W., & Lawrence Moss, R. (2010). Necrotizing Enterocolitis. In D. J. Ostlie (Ed.), Ashcraft’s pediatric surgery (5th ed., pp. 439–455). Philadelphia: W.B. Saunders.

    Chapter  Google Scholar 

  • Himelright, I., Harris, E., Lorch, V., Anderson, M., Jones, T., Craig, A., Kuehnert, M., Forster, T., Arduino, M., & Jensen, B. (2002). Enterobacter sakazakii infections associated with the use of powdered infant formula-Tennessee, 2001. Morbidity and Mortality Weekly Report. CDC, 51, 297–300. Available: http://www.cdc.gov/Mmwr/PDF/wk/mm5114.pdf. Accessed 13 Oct 2014.

  • Hochel, I., RĹŻĹľiÄŤková, H., KrásnĂ˝, L., & Demnerová, K. (2012). Occurrence of Cronobacter spp. in retail foods. Journal of Applied Microbiology, 112, 1257–1265.

    Article  CAS  PubMed  Google Scholar 

  • Holman, R. C., Stoll, B. J., Curns, A. T., Yorita, K. L., Steiner, C. A., & Schonberger, L. B. (2006). Necrotising enterocolitis hospitalisations among neonates in the United States. Paediatric and Perinatal Epidemiology, 20, 498–506.

    Article  PubMed  Google Scholar 

  • HolĂ˝, O., & Forsythe, S. (2014). Cronobacter spp. as emerging causes of healthcare-associated infection. Journal of Hospital Infection, 86, 169–177.

    Article  PubMed  Google Scholar 

  • Howkins, R. E., Lissner, C. R., & Sanford, J. P. (1991). Enterobacter sakazakii bacteremia in an adult. Southern Medical Journal, 84, 793.

    Article  Google Scholar 

  • Hunter, C., & Bean, J. (2013). Cronobacter: An emerging opportunistic pathogen associated with neonatal meningitis, sepsis and necrotizing enterocolitis. Journal of Perinatology, 33, 581–585.

    Article  CAS  PubMed  Google Scholar 

  • Hunter, C. J., Singamsetty, V. K., Chokshi, N. K., Boyle, P., Camerini, V., Grishin, A. V., Upperman, J. S., Ford, H. R. & Prasadarao, N. V. (2008). Enterobacter sakazakii enhances epithelial cell injury by inducing apoptosis in a rat model of necrotizing enterocolitis. Journal of Infectious Diseases, 198, 586.

    Google Scholar 

  • Hunter, C. J., Williams, M., Petrosyan, M., Guner, Y., Mittal, R., Mock, D., Upperman, J. S., Ford, H. R., & Prasadarao, N. V. (2009). 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. Infection and Immunity, 77, 1031–1043.

    Article  CAS  PubMed  Google Scholar 

  • Hurrell, E., Kucerova, E., Loughlin, M., Caubilla-Barron, J., Hilton, A., Armstrong, R., Smith, C., Grant, J., Shoo, S., & Forsythe, S. (2009). Neonatal enteral feeding tubes as loci for colonisation by members of the Enterobacteriaceae. BMC Infectious Diseases, 9, 146.

    Article  PubMed  PubMed Central  Google Scholar 

  • Iben, S., & Rodriguez, R. (2011). Neonatal necrotizing enterocolitis. In Pediatric gastrointestinal and liver disease (4th ed., pp. 512–520). Saint Louis: W.B. Saunders.

    Google Scholar 

  • Iversen, C., Lehner, A., Mullane, N., Bidlas, E., Cleenwerck, I., Marugg, J., Fanning, S., Stephan, R., & Joosten, H. (2007). The taxonomy of Enterobacter sakazakii: Proposal of a new genus Cronobacter gen. Nov. and descriptions of Cronobacter sakazakii comb. Nov. Cronobacter sakazakii subsp. sakazakii, comb. Nov., Cronobacter sakazakii subsp. malonaticus subsp. nov., Cronobacter turicensis sp. nov., Cronobacter muytjensii sp. nov., Cronobacter dublinensis sp. nov. and Cronobacter genomospecies 1. BMC Evolutionary Biology, 7, 64.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jackson, E. E., Flores, J. P., Fernández-EscartĂ­n, E., & Forsythe, S. J. (2015a). Reevaluation of a suspected Cronobacter sakazakii outbreak in Mexico. Journal of Food Protection, 78, 1191–1196.

    Article  PubMed  Google Scholar 

  • Jackson, E. E., Masood, N., Ibrahim, K., Urvoy, N., Hariri, S., & Forsythe, S. J. (2015b). Description of Siccibacter colletis sp. nov., a novel species isolated from plant material, and emended description of Siccibacter turicensis. International Journal of Systematic and Evolutionary Microbiology, 65, 1335–1341.

    Article  CAS  PubMed  Google Scholar 

  • Jaradat, Z. W., Ababneh, Q. O., Saadoun, I. M., Samara, N. A. & Rashdan, A. M. (2009). Isolation of Cronobacter spp. (formerly Enterobacter sakazakii) from infant food, herbs and environmental samples and the subsequent identification and confirmation of the isolates using biochemical, chromogenic assays, PCR and 16S rRNA sequencing. BMC microbiology, 9, 225.

    Google Scholar 

  • JimĂ©nez, E. B., & GimĂ©nez, C. R. (1982). Septic shock due to Enterobacter sakazakii. Clinical Microbiology Newsletter, 4, 30.

    Article  Google Scholar 

  • Joker, R., Norholm, T., & Siboni, K. (1965). A case of neonatal meningitis caused by a yellow Enterobacter. Danish Medical Bulletin, 12, 128.

    CAS  PubMed  Google Scholar 

  • Joseph, S., Cetinkaya, E., Drahovska, H., Levican, A., Figueras, M. J., & Forsythe, S. J. (2012a). Cronobacter condimenti sp. nov., isolated from spiced meat, and Cronobacter universalis sp. nov., a species designation for Cronobacter sp. genomospecies 1, recovered from a leg infection, water and food ingredients. International Journal of Systematic and Evolutionary Microbiology, 62, 1277–1283.

    Article  CAS  PubMed  Google Scholar 

  • Joseph, S., Desai, P., Ji, Y., Cummings, C. A., Shih, R., Degoricija, L., Rico, A., Brzoska, P., Hamby, S. E., Masood, N., Hariri, S., Sonbol, H., Chuzhanova, N., McClelland, M., Furtado, M. R., & Forsythe, S. J. (2012b). Comparative analysis of genome sequences covering the seven Cronobacter species. PloS One, 7, e49455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joseph, S., & Forsythe, S. J. (2011). Predominance of Cronobacter sakazakii sequence type 4 in neonatal infections. Emerging Infectious Diseases, 17, 1713–1715.

    Article  PubMed  PubMed Central  Google Scholar 

  • Joseph, S., Hariri, S., Masood, N., & Forsythe, S. (2013). Sialic acid utilization by Cronobacter sakazakii. Microbial Informatics and Experimentation, 3, 1–11.

    Article  CAS  Google Scholar 

  • Kandhai, M. C., Reij, M. W., Gorris, L. G., Guillaume-Gentil, O., & van Schothorst, M. (2004). Occurrence of Enterobacter sakazakii in food production environments and households. The Lancet, 363, 39–40.

    Article  Google Scholar 

  • Kilonzo-Nthenge, A., Chen, F.-C., & Godwin, S. L. (2008). Occurrence of Listeria and Enterobacteriaceae in domestic refrigerators. Journal of Food Protection, 71, 608–612.

    Article  PubMed  Google Scholar 

  • Kim, K., Kim, K. P., Choi, J., Lim, J. A., Lee, J., Hwang, S., & Ryu, S. (2010). Outer membrane proteins a (OmpA) and X (OmpX) are essential for basolateral invasion of Cronobacter sakazakii. Applied and Environmental Microbiology, 76, 5188–5198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, K. P., & Loessner, M. J. (2008). Enterobacter sakazakii invasion in human intestinal Caco-2 cells requires the host cell cytoskeleton and is enhanced by disruption of tight junction. Infection and Immunity, 76, 562–570.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S., Hwang, H., Kim, K. P., Yoon, H., Kang, D. H., & Ryu, S. (2015). hfq plays important roles in virulence and stress adaptation in Cronobacter sakazakii ATCC 29544. Infection and Immunity, 83, 2089–2098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kothary, M., McCardell, B., Frazar, C., Deer, D., & Tall, B. (2007). Characterization of the zinc-containing metalloprotease encoded by zpx and development of a species-specific detection method for Enterobacter sakazakii. Applied and Environmental Microbiology, 73, 4142–4151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kröncke, K.-D., Fehsel, K., & Kolb-Bachofen, V. (1997). Nitric oxide: Cytotoxicity versus cytoprotection—How, why, when, and where? Nitric Oxide: Biology and Chemistry, 1, 107–120.

    Article  Google Scholar 

  • Kucerova, E., Clifton, S. W., Xia, X. Q., Long, F., Porwollik, S., Fulton, L., Fronick, C., Minx, P., Kyung, K., Warren, W., Fulton, R., Feng, D., Wollam, A., Shah, N., Bhonagiri, V., Nash, W. E., Hallsworth-Pepin, K., Wilson, R. K., McClelland, M., & Forsythe, S. J. (2010). Genome sequence of Cronobacter sakazakii BAA-894 and comparative genomic hybridization analysis with other Cronobacter species. PloS One, 5, e9556.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kucerova, E., Joseph, S., & Forsythe, S. (2011). The Cronobacter genus: Ubiquity and diversity. Quality Assurance & Safety of Crops and Food, 3, 104–122.

    Article  CAS  Google Scholar 

  • Lähteenmäki, K., Edelman, S., & Korhonen, T. K. (2005). Bacterial metastasis: The host plasminogen system in bacterial invasion. Trends in Microbiology, 13, 79–85.

    Article  PubMed  CAS  Google Scholar 

  • Lai, K. K. (2001). Enterobacter sakazakii infections among neonates, infants, children, and adults: Case reports and a review of the literature. Medicine, 80, 113–122.

    Article  CAS  PubMed  Google Scholar 

  • Li, Q., Zhao, W.-D., Zhang, K., Fang, W.-G., Hu, Y., Wu, S.-H., & Chen, Y.-H. (2010). PI3K-dependent host cell actin rearrangements are required for Cronobacter sakazakii invasion of human brain microvascular endothelial cells. Medical Microbiology and Immunology, 199, 333–340.

    Article  CAS  PubMed  Google Scholar 

  • Liu, D.-X., Zhao, W.-D., Fang, W.-G., & Chen, Y.-H. (2012a). cPLA 2 α-mediated actin rearrangements downstream of the Akt signaling is required for Cronobacter sakazakii invasion into brain endothelial cells. Biochemical and Biophysical Research Communications, 417, 925–930.

    Article  CAS  PubMed  Google Scholar 

  • Liu, H., Yang, Y., Cui, J., Liu, L., Liu, H., Hu, G., Shi, Y., & Li, J. (2013). Evaluation and implementation of a membrane filter method for Cronobacter detection in drinking water. FEMS Microbiology Letters, 344, 60–68.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Q., Mittal, R., Emami, C. N., Iversen, C., Ford, H. R., & Prasadarao, N. V. (2012b). Human isolates of Cronobacter sakazakii bind efficiently to intestinal epithelial cells in vitro to induce monolayer permeability and apoptosis. Journal of Surgical Research, 176, 437–447.

    Article  CAS  PubMed  Google Scholar 

  • Mange, J. P., Stephan, R., Borel, N., Wild, P., Kim, K. S., Pospischil, A., & Lehner, A. (2006). Adhesive properties of Enterobacter sakazakii to human epithelial and brain microvascular endothelial cells. BMC Microbiology, 6, 58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mayer, B., & Hemmens, B. (1997). Biosynthesis and action of nitric oxide in mammalian cells. Trends in Biochemical Sciences, 22, 477–481.

    Article  CAS  PubMed  Google Scholar 

  • Minor, T., Lasher, A., Klontz, K., Brown, B., Nardinelli, C., & Zorn, D. (2015). The per case and Total annual costs of foodborne illness in the United States. Risk Analysis, 35, 1125–1139.

    Article  PubMed  Google Scholar 

  • Mittal, R., Bulgheresi, S., Emami, C., & Prasadarao, N. V. (2009a). Enterobacter sakazakii targets DC-SIGN to induce immunosuppressive responses in dendritic cells by modulating MAPKs. The Journal of Immunology, 183, 6588–6599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mittal, R., Wang, Y., Hunter, C. J., Gonzalez-Gomez, I., & Prasadarao, N. V. (2009b). Brain damage in newborn rat model of meningitis by Enterobacter sakazakii: A role for outer membrane protein a. Laboratory Investigation, 89, 263–277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muytjens, H., Zanen, H., Sonderkamp, H., Kollee, L., Wachsmuth, I. K., & Farmer, J. (1983). Analysis of eight cases of neonatal meningitis and sepsis due to Enterobacter sakazakii. Journal of Clinical Microbiology, 18, 115–120.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nair, M. K. M., & Venkitanarayanan, K. (2007). Role of bacterial OmpA and host cytoskeleton in the invasion of human intestinal epithelial cells by Enterobacter sakazakii. Pediatric Research, 62, 664–669.

    Article  CAS  Google Scholar 

  • Nair, M. K. M., Venkitanarayanan, K., Silbart, L. K., & Kim, K. S. (2009). Outer membrane protein a (OmpA) of Cronobacter sakazakii binds fibronectin and contributes to invasion of human brain microvascular endothelial cells. Foodborne Pathogens and Disease, 6, 495–501.

    Article  PubMed  CAS  Google Scholar 

  • Ogrodzki, P., & Forsythe, S. (2015). Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. Malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis. BMC Genomics, 16, 758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pagotto, F. J., Nazarowec-White, M., Bidawid, S., & Farber, J. M. (2003). Enterobacter sakazakii: Infectivity and enterotoxin production in vitro and in vivo. Journal of Food Protection, 66, 370–375.

    Article  PubMed  Google Scholar 

  • Parrow, N. L., Fleming, R. E., & Minnick, M. F. (2013). Sequestration and scavenging of iron in infection. Infection and Immunity, 81, 3503–3514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patrick, M. E., Mahon, B. E., Greene, S. A., Rounds, J., Cronquist, A., Wymore, K., Boothe, E., Lathrop, S., Palmer, A., & Bowen, A. (2014). Incidence of Cronobacter spp. infections, United States, 2003-2009. Emerging Infectious Diseases, 20, 1536–1539.

    Article  Google Scholar 

  • Raghav, M., & Aggarwal, P. (2007). Purification and characterization of Enterobacter sakazakii enterotoxin. Canadian Journal of Microbiology, 53, 750–755.

    Article  CAS  PubMed  Google Scholar 

  • Ravisankar, S., Syed, S., Garg, P., & Higginson, J. (2014). Is Cronobacter sakazakii infection possible in an exclusively breastfed premature neonate in the neonatal intensive care unit? Journal of Perinatology, 34, 408–409.

    Article  CAS  PubMed  Google Scholar 

  • Sellner, J., Täuber, M. G., & Leib, S. L. (2010). Pathogenesis and pathophysiology of bacterial CNS infections. In K. L. Roos & A. R. Tunkel (Eds.), Handbook of clinical neurology (pp. 1–16). Philadelphia: PA: Elsevier.

    Google Scholar 

  • Singamsetty, V. K., Wang, Y., Shimada, H., & Prasadarao, N. V. (2008). Outer membrane protein a expression in Enterobacter sakazakii is required to induce microtubule condensation in human brain microvascular endothelial cells for invasion. Microbial Pathogenesis, 45, 181–191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stephan, R., Lehner, A., Tischler, P., & Rattei, T. (2011). Complete genome sequence of Cronobacter turicensis LMG 23827, a food-borne pathogen causing deaths in neonates. Journal of Bacteriology, 193, 309–310.

    Article  CAS  PubMed  Google Scholar 

  • Stoll, B. J., Hansen, N., Fanaroff, A. A., & Lemons, J. A. (2004). Enterobacter sakazakii is a rare cause of neonatal septicemia or meningitis in VLBW infants. The Journal of Pediatrics, 144, 821–823.

    PubMed  Google Scholar 

  • Suppiger, A., Eshwar, A. K., Stephan, R., Kaever, V., Eberl, L., & Lehner, A. (2016). The DSF type quorum sensing signalling system RpfF/R regulates diverse phenotypes in the opportunistic pathogen Cronobacter. Scientific Reports, 6, 18753–18753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka, M., Sotomatsu, A., Yoshida, T., Hirai, S., & Nishida, A. (1994). Detection of superoxide production by activated microglia using a sensitive and specific chemiluminescence assay and microglia-mediated PC12h cell death. Journal of Neurochemistry, 63, 266–270.

    Article  CAS  PubMed  Google Scholar 

  • Teramoto, S., Tanabe, Y., Okano, E., Nagashima, T., Kobayashi, M., & Etoh, Y. (2010). A first fatal neonatal case of Enterobacter sakazakii infection in Japan. Pediatrics International, 52, 312–313.

    Article  PubMed  Google Scholar 

  • Townsend, S., Caubilla Barron, J., Loc-Carrillo, C., & Forsythe, S. (2007a). 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 Microbiology, 24, 67–74.

    Article  CAS  PubMed  Google Scholar 

  • Townsend, S., Hurrell, E., Gonzalez-Gomez, I., Lowe, J., Frye, J. G., Forsythe, S., & Badger, J. L. (2007b). Enterobacter sakazakii invades brain capillary endothelial cells, persists in human macrophages influencing cytokine secretion and induces severe brain pathology in the neonatal rat. Microbiology, 153, 3538–3547.

    Article  CAS  PubMed  Google Scholar 

  • Townsend, S. M., Hurrell, E., Caubilla-Barron, J., Loc-Carrillo, C., & Forsythe, S. J. (2008). Characterization of an extended-spectrum beta-lactamase Enterobacter hormaechei nosocomial outbreak, and other Enterobacter hormaechei misidentified as Cronobacter (Enterobacter) sakazakii. Microbiology, 154, 3659–3667.

    Article  CAS  PubMed  Google Scholar 

  • Urmenyi, A. M. C., & Franklin, A. W. (1961). Neonatal death from pigmented coliform infection. The Lancet, 277, 313–315.

    Article  Google Scholar 

  • van Acker, J., de Smet, F., Muyldermans, G., Bougatef, A., Naessens, A. & Lauwers, S. (2001). Outbreak of necrotizing enterocolitis associated with Enterobacter sakazakii in powdered milk formula. Journal of clinical microbiology, 39, 293–297.

    Google Scholar 

  • Wilson, M., McNab, R., & Henderson, B. (2002). Bacterial disease mechanisms: An introduction to cellular microbiology. New York: Cambridge University Press.

    Book  Google Scholar 

  • Yan, Q., Condell, O., Power, K., Butler, F., Tall, B., & Fanning, S. (2012). Cronobacter species (formerly known as Enterobacter sakazakii) in powdered infant formula: A review of our current understanding of the biology of this bacterium. Journal of Applied Microbiology, 113, 1–15.

    Article  CAS  PubMed  Google Scholar 

  • Yang, J., Wei, L., Gu, M., Fang, X., & Yang, P. (2009). Identification of proteins involved in infectivity and enterotoxin production in Enterobacter sakazakii. Journal of Rapid Methods and Automation in Microbiology, 17, 164–181.

    Article  CAS  Google Scholar 

  • Yoshida, T., Tanaka, M., Sotomatsu, A., & Hirai, S. (1995). Activated microglia cause superoxide-mediated release of iron from ferritin. Neuroscience Letters, 190, 21–24.

    Article  CAS  PubMed  Google Scholar 

  • Zlokovic, B. V. (2008). The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron, 57, 178–201.

    Google Scholar 

Download references

Acknowledgments

The work was in part funded by King Saud bin Abdulaziz University for Health Sciences and the Saudi Arabian Cultural Bureau in London.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F. S. Almajed .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Almajed, F.S., Forsythe, S. (2017). Virulence Traits in the Cronobacter Genus. In: Gurtler, J., Doyle, M., Kornacki, J. (eds) Foodborne Pathogens. Food Microbiology and Food Safety(). Springer, Cham. https://doi.org/10.1007/978-3-319-56836-2_5

Download citation

Publish with us

Policies and ethics