Abstract
Lactoferrin (LF) has in vitro antimicrobial activity against Gram-negative bacteria. Salmonella enterica subsp. enterica serovar Typhimurium causes systemic infection and acute diarrhea in humans, mainly in children younger than 2 years of age. The aim of the study was to determine the in vivo effect of bovine LF in Salmonella ser. Typhimurium infection in mice. 58 BALB/c mice were employed. Two hours before the infection with 300 μl of 107 CFU of Salmonella ser. Typhimurium, 29 mice received LF (2 mg) and 29 placebo (buffer). After the infection, the mice received LF (10 mg/ml) ad libitum or buffer, respectively, for 7 days. Mortality, weight and clinical signs (piloerection, hunched position and reduced movement) were monitored daily. The degree of inflammation and necrosis in the intestine, liver, spleen and brain were studied with a blinded observer. The mortality in the control group (8/29) was higher than in the LF group (1/29) (Kapplan Meier P < 0.05). From the third day post-infection the control group were significantly more symptomatic (P < 0.05). The blood culture for Salmonella spp. was positive for all mice studied in the control group (17/17), but positive in the LF group in only 6/17 animals (P < 0.05). In the LF group, the pathologic studies show less inflammation and focal necrosis in the four organs studied, with the greatest difference found in the intestine. Bovine LF protects against Salmonella ser. Typhimurium infection in mice, reducing the severity, mortality and the degree of inflammation of this infection.
Similar content being viewed by others
References
Appelmelk BJ, An YQ, Geerts M, Thijs BG, de Boer HA, MacLaren DM, de Graaff J, Nuijens JH (1994) Lactoferrin is a lipid A-binding protein. Infect Immun 62(6):2628–2632
Bessler HC, de Oliveira IR, Giugliano LG (2006) Human milk glycoproteins inhibit the adherence of Salmonella typhimurium to HeLa cells. Microbiol Immunol 50(11):877–882
Brandenburg K, Jurgens G, Muller M, Fukuoka S, Koch MH (2001) Biophysical characterization of lipopolysaccharide and lipid A inactivation by lactoferrin. Biol Chem 382(8):1215–1225. doi:10.1515/BC.2001.152
Coombes BK, Coburn BA, Potter AA, Gomis S, Mirakhur K, Li Y, Finlay BB (2005) Analysis of the contribution of Salmonella pathogenicity islands 1 and 2 to enteric disease progression using a novel bovine ileal loop model and a murine model of infectious enterocolitis. Infect Immun 73(11):7161–7169. doi:10.1128/IAI.73.11.7161-7169.2005
Ellison RT 3rd, Giehl TJ, LaForce FM (1988) Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin. Infect Immun 56(11):2774–2781
Gomez HF, Ochoa TJ, Herrera-Insua I, Carlin LG, Cleary TG (2002) Lactoferrin protects rabbits from Shigella flexneri-induced inflammatory enteritis. Infect Immun 70(12):7050–7053
Haraga A, Ohlson MB, Miller SI (2008) Salmonellae interplay with host cells. Nat Rev Microbiol 6(1):53–66. doi:10.1038/nrmicro1788
Hsu HS (1989) Pathogenesis and immunity in murine salmonellosis. Microbiol Rev 53(4):390–409
Kusters JG, Mulders-Kremers GA, van Doornik CE, van der Zeijst BA (1993) Effects of multiplicity of infection, bacterial protein synthesis, and growth phase on adhesion to and invasion of human cell lines by Salmonella typhimurium. Infect Immun 61(12):5013–5020
MP Foley B, De Lappe N, Cormican M (2006) Salmonellosis in Ireland. Epi-Insight 8(10):2–3
Naidu SS, Svensson U, Kishore AR, Naidu AS (1993) Relationship between antibacterial activity and porin binding of lactoferrin in Escherichia coli and Salmonella typhimurium. Antimicrob Agents Chemother 37(2):240–245
Nilsson AI, Kugelberg E, Berg OG, Andersson DI (2004) Experimental adaptation of Salmonella typhimurium to mice. Genetics 168(3):1119–1130. doi:10.1534/genetics.104.030304
Norel F, Coynault C, Miras I, Hermant D, Popoff MY (1989) Cloning and expression of plasmid DNA sequences involved in Salmonella serotype typhimurium virulence. Mol Microbiol 3(6):733–743
Ochoa TJ, Cleary TG (2009) Effect of lactoferrin on enteric pathogens. Biochimie 91(1):30–34. doi:10.1016/j.biochi.2008.04.006
Ochoa TJ, Noguera-Obenza M, Ebel F, Guzman CA, Gomez HF, Cleary TG (2003) Lactoferrin impairs type III secretory system function in enteropathogenic Escherichia coli. Infect Immun 71(9):5149–5155
Ochoa TJ, Brown EL, Guion CE, Chen JZ, McMahon RJ, Cleary TG (2006) Effect of lactoferrin on enteroaggregative E. coli (EAEC). Biochem Cell Biol 84(3):369–376. doi:10.1139/o06-053
Pardon P, Popoff MY, Coynault C, Marly J, Miras I (1986) Virulence-associated plasmids of Salmonella serotype Typhimurium in experimental murine infection. Ann Inst Pasteur Microbiol 137B(1):47–60
Sansonetti PJ (2004) War and peace at mucosal surfaces. Nat Rev Immunol 4(12):953–964. doi:10.1038/nri1499
Sebastiani G, Blais V, Sancho V, Vogel SN, Stevenson MM, Gros P, Lapointe JM, Rivest S, Malo D (2002) Host immune response to Salmonella enterica serovar Typhimurium infection in mice derived from wild strains. Infect Immun 70(4):1997–2009
Sorimachi K, Akimoto K, Hattori Y, Ieiri T, Niwa A (1997) Activation of macrophages by lactoferrin: secretion of TNF-alpha, IL-8 and NO. Biochem Mol Biol Int 43(1):79–87
Vazquez-Torres A, Jones-Carson J, Baumler AJ, Falkow S, Valdivia R, Brown W, Le M, Berggren R, Parks WT, Fang FC (1999) Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature 401(6755):804–808. doi:10.1038/44593
Vidal S, Tremblay ML, Govoni G, Gauthier S, Sebastiani G, Malo D, Skamene E, Olivier M, Jothy S, Gros P (1995) The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene. J Exp Med 182(3):655–666
Wickham ME, Brown NF, Provias J, Finlay BB, Coombes BK (2007) Oral infection of mice with Salmonella enterica serovar Typhimurium causes meningitis and infection of the brain. BMC Infect Dis 7:65. doi:10.1186/1471-2334-7-65
Zagulski T, Lipinski P, Zagulska A, Broniek S, Jarzabek Z (1989) Lactoferrin can protect mice against a lethal dose of Escherichia coli in experimental infection in vivo. Br J Exp Pathol 70(6):697–704
Acknowledgments
This work was partially funded by Universidad Peruana Cayetano Heredia Institutional Research Funds (Fondo Concursable 2005). Dr. T. Ochoa is supported by 1K01TW007405; Dr. T. Cleary is supported by R01-HD051716.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mosquito, S., Ochoa, T.J., Cok, J. et al. Effect of bovine lactoferrin in Salmonella ser. Typhimurium infection in mice. Biometals 23, 515–521 (2010). https://doi.org/10.1007/s10534-010-9325-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10534-010-9325-1