Bacteriostatic activity of human lactoferrin against Staphylococcus aureus is a function of its iron-binding properties and is not influenced by antibiotic resistance

Aguila, Antonio

doi:10.1016/s0928-8244(01)00253-x

Cited by 25 publications

(29 citation statements)

References 19 publications

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“…2B). Taken together, these data confirm the findings of other workers, who showed that Lf is bactericidal only in its iron-free state (1,5,14) and that the bactericidal nature of the native Lf preparations is due to Lf rather than a contaminant.…”

Section: Isda Is An Lf Binding Proteinsupporting

confidence: 91%

“…Binding of iron has been shown to significantly alter the structural conformation of Lf (29), which correlates with a loss of both protease and antibacterial activities against a number of organisms, including S. aureus (1,4,14,66). In this study, we showed that inhibition of serine protease activity abrogates killing activity.…”

Section: Vol 76 2008mentioning

confidence: 56%

“…Expression of IsdA inhibits killing of S. aureus by aLf. We hypothesized that expression of IsdA on the surface of S. aureus would alter the sensitivity of the organism to Lf, which is known to be bactericidal (1,4,14,66). To test this, aLf and hLf isolated from human milk were used in killing assays.…”

Section: Isda Is An Lf Binding Proteinmentioning

confidence: 99%

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IsdA ProtectsStaphylococcus aureusagainst the Bactericidal Protease Activity of Apolactoferrin

Clarke

Foster

2008

Infect Immun

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An important facet of the Staphylococcus aureus host-pathogen interaction is the ability of the invading bacterium to evade host innate defenses, particularly the cocktail of host antimicrobial peptides. In this work, we showed that IsdA, a surface protein of S. aureus which is required for nasal colonization, binds to lactoferrin, the most abundant antistaphylococcal polypeptide in human nasal secretions. The presence of IsdA on the surface of S. aureus confers resistance to killing by lactoferrin. In addition, the bactericidal activity of lactoferrin was inhibited by addition of phenylmethylsulfonyl fluoride, implicating the serine protease activity of lactoferrin in the killing of S. aureus. Recombinant IsdA was a competitive inhibitor of lactoferrin protease activity. Reciprocally, antibody reactive to IsdA enhanced killing of S. aureus. Thus, IsdA can protect S. aureus against lactoferrin and acts as a protease inhibitor.

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Section: Isda Is An Lf Binding Proteinsupporting

confidence: 91%

Section: Vol 76 2008mentioning

confidence: 56%

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IsdA ProtectsStaphylococcus aureusagainst the Bactericidal Protease Activity of Apolactoferrin

Clarke

Foster

2008

Infect Immun

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“…This may contribute to the observed protective effect of oral LF ingestion since indomethacin-induced enteropathy is in part caused by oxidative stress in the epithelium. The ferrochelating properties of LF also result in antimicrobial activity of LF in human plasma serum, as iron deprivation inhibits bacterial growth (Aguila et al, 2001). Additionally, LF exerts bactericidal activity against antibiotic-resistant bacteria in vitro independent of its iron-binding capacity (Bellamy et al, 1992;Nibbering et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

2003

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Objective: To determine whether recombinant human lactoferrin ingestion inhibits nonsteroidal antiinflammatory drugs (NSAID)-induced gastroenteropathy in vivo in healthy volunteers as a model for disorders associated with a rise in permeability of the stomach and the small intestine. Design: A randomized crossover dietary intervention. Subjects and interventions: In all, 15 healthy volunteers (age 2371.4 y) were tested. A sucrose and a lactulose/rhamnose (L/R) permeability test was performed to assess gastroduodenal and small intestine permeability as indicator of NSAID-induced gastroenteropathy. All subjects consumed standardized meals for 2 days. On the second day at time ¼ À24 h each subject ingested a drink containing 5 g recombinant human lactoferrin or placebo during breakfast. At t ¼ À9 h, subjects ingested the same drink with 75 mg of the NSAID indomethacin and after an overnight fast at t ¼ À1 h subjects consumed the drink and 50 mg indomethacin. After 1 h, at t ¼ 0, a permeability test was performed. Results: Small intestine permeability after indomethacin and placebo was significantly higher (L/R ratio ¼ 0.036; 0.014-0.092, Po0.05) compared to the permeability observed after ingestion of indomethacin and lactoferrin (0.028; 0.015-0.056), whereas gastroduodenal permeability did not differ between the two interventions (P ¼ 0.3). Conclusion: Oral recombinant human lactoferrin supplementation during a short-term indomethacin challenge reduced the NSAID-mediated increase in small intestinal permeability and hence may provide a nutritional tool in the treatment of hyperpermeability-associated disorders. Sponshorship: Grant and human recombinant lactoferrin donated from Agennix Inc., Houston, TX.

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“…This protein inhibits the growth of many Gram-positive and Gram-negative bacteria, as well as some species of mold and yeast. Aguila et al (2001) demonstrated that therapeutic approaches based on the use of ferrochelating agents such as lactoferrin combined with antimicrobial drugs may help to counteract the reduced efficacy of current antibiotics. Lee et al (1998) evaluated the ability of lactoferring to protect germ-free, colostrumsdeprived piglets against a lethal intravenous challenge with endotoxin ; it was shown that prefeeding with lactoferrin resulted in a significant decrease in piglet mortality compared to feeding with bovine serum albumin.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Recombinant Human Lactoferricin Culture as a Substitute for Antibiotic in Pig Starter Diets

Hong¹,

Kim²,

Hwang³

et al. 2003

Journal of Animal Science and Technology

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Sixty [(Duroc×Yorkshire)×Landrace] pigs (7.63±0.41kg average body weight and 25-d average age) were used in a 20-d growth assay to determine the effect of dietary recombinant human lactoferricin culture (RHLC) supplementation on growth performance, digestibility and plasma IgG concentration in weaning pigs. Dietary treatments included 1) Negative control (NC : without antibiotic), 2) Positive control (PC : NC diet + 0.1% chlortetracycline), 3) RHLC0.3 (NC diet + 0.3% RHLC), 4) RHLC0.5 (NC diet + 0.5% RHLC). No differences were found among treatments in average daily gain (P 0.05). ADFI of pigs fed RHLC0.3 diet was higher than that of pigs fed PC diet (P 0.05). However, pigs fed RHLC0.5 diet had improved gain/feed compared to pigs fed PC diet. Pigs fed PC and RHLC diets showed significantly increased dry matter digestibility compared to pigs fed NC diet (P 0.05). There was no significant difference in plasma IgG concentrations (P 0.05). The supplementation of RHLC in starter pig diets appears to be an alternative to antibiotics.

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Bacteriostatic activity of human lactoferrin against Staphylococcus aureus is a function of its iron-binding properties and is not influenced by antibiotic resistance

Cited by 25 publications

References 19 publications

IsdA ProtectsStaphylococcus aureusagainst the Bactericidal Protease Activity of Apolactoferrin

IsdA ProtectsStaphylococcus aureusagainst the Bactericidal Protease Activity of Apolactoferrin

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

Evaluation of Recombinant Human Lactoferricin Culture as a Substitute for Antibiotic in Pig Starter Diets

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