Antibacterial activity in human amniotic fluid: dependence on divalent cations

Scane, T. M. N.; Hawkins, D. F.

doi:10.1111/j.1471-0528.1986.tb07956.x

Cited by 10 publications

(4 citation statements)

References 13 publications

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“…We next analyzed the growth of strain NEM316 in human AF. AF has been reported to have antimicrobial properties toward various species of bacteria due to β-lysin and lysozyme activity, which depends on divalent cations such as zinc and phosphate [14], [15]. In multiple studies reported in the literature 18–73% of AF samples exhibited inhibitory properties towards various bacterial species.…”

Section: Resultsmentioning

confidence: 99%

Transcriptome Adaptation of Group B Streptococcus to Growth in Human Amniotic Fluid

et al. 2009

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Background Streptococcus agalactiae (group B Streptococcus) is a bacterial pathogen that causes severe intrauterine infections leading to fetal morbidity and mortality. The pathogenesis of GBS infection in this environment is poorly understood, in part because we lack a detailed understanding of the adaptation of this pathogen to growth in amniotic fluid. To address this knowledge deficit, we characterized the transcriptome of GBS grown in human amniotic fluid (AF) and compared it with the transcriptome in rich laboratory medium.MethodsGBS was grown in Todd Hewitt-yeast extract medium and human AF. Bacteria were collected at mid-logarithmic, late-logarithmic and stationary growth phase. We performed global expression microarray analysis using a custom-made Affymetrix GeneChip. The normalized hybridization values derived from three biological replicates at each growth point were obtained. AF/THY transcript ratios representing greater than a 2-fold change and P-value exceeding 0.05 were considered to be statistically significant.Principal FindingsWe have discovered that GBS significantly remodels its transcriptome in response to exposure to human amniotic fluid. GBS grew rapidly in human AF and did not exhibit a global stress response. The majority of changes in GBS transcripts in AF compared to THY medium were related to genes mediating metabolism of amino acids, carbohydrates, and nucleotides. The majority of the observed changes in transcripts affects genes involved in basic bacterial metabolism and is connected to AF composition and nutritional requirements of the bacterium. Importantly, the response to growth in human AF included significant changes in transcripts of multiple virulence genes such as adhesins, capsule, and hemolysin and IL-8 proteinase what might have consequences for the outcome of host-pathogen interactions.Conclusions/SignificanceOur work provides extensive new information about how the transcriptome of GBS responds to growth in AF, and thus new leads for pathogenesis research.

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Section: Resultsmentioning

confidence: 99%

Transcriptome Adaptation of Group B Streptococcus to Growth in Human Amniotic Fluid

et al. 2009

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“…Despite the broad activity of host-derived peptides, their potency is often optimal only under specific conditions. For instance, several CAPs, although highly active in phosphate buffer, display a significant decrease in antibacterial potency in the presence of physiological concentrations of NaCl and divalent cations (11,42,51,56,58,62). In some cases (e.g., cystic fibrosis airway fluids), hypo-osmolar NaCl may be sufficient to significantly suppress antimicrobial function (25).…”

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confidence: 99%

Activity of the De Novo Engineered Antimicrobial Peptide WLBU2 against Pseudomonas aeruginosa in Human Serum and Whole Blood: Implications for Systemic Applications

Deslouches

Islam

Craigo

et al. 2005

Antimicrob Agents Chemother

137

161

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Cationic amphipathic peptides have been extensively investigated as a potential source of new antimicrobials that can complement current antibiotic regimens in the face of emerging drug-resistant bacteria. However, the suppression of antimicrobial activity under certain biologically relevant conditions (e.g., serum and physiological salt concentrations) has hampered efforts to develop safe and effective antimicrobial peptides for clinical use. We have analyzed the activity and selectivity of the human peptide LL37 and the de novo engineered antimicrobial peptide WLBU2 in several biologically relevant conditions. The host-derived synthetic peptide LL37 displayed high activity against Pseudomonas aeruginosa but demonstrated staphylococcusspecific sensitivity to NaCl concentrations varying from 50 to 300 mM. Moreover, LL37 potency was variably suppressed in the presence of 1 to 6 mM Mg 2؉ and Ca 2؉ ions. In contrast, WLBU2 maintained its activity in NaCl and physiologic serum concentrations of Mg 2؉ and Ca 2؉ . WLBU2 is able to kill P. aeruginosa (10 6 CFU/ml) in human serum, with a minimum bactericidal concentration of <9 M. Conversely, LL37 is inactive in the presence of human serum. Bacterial killing kinetic assays in serum revealed that WLBU2 achieved complete bacterial killing in 20 min. Consistent with these results was the ability of WLBU2 (15 to 20 M) to eradicate bacteria from ex vivo samples of whole blood. The selectivity of WLBU2 was further demonstrated by its ability to specifically eliminate P. aeruginosa in coculture with human monocytes or skin fibroblasts without detectable adverse effects to the host cells. Finally, WLBU2 displayed potent efficacy against P. aeruginosa in an intraperitoneal infection model using female Swiss Webster mice. These results establish a potential application of WLBU2 in the treatment of bacterial sepsis.

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“…Medium-related activity losses have been reported before for NK-2 [25,26,28] as well as for other HDPs [59][60][61][62]. In principle, besides proteolysis, binding to serum components [63][64][65][66] as well as electrostatic interference from elevated concentrations of salts and metal ions [67][68][69][70][71] bears the potential to decrease peptide effectiveness in medium. However, such mechanisms would have likewise impeded the activity of any peptide tested here, which in fact was not observed.…”

Section: Discussionmentioning

confidence: 87%

Comparison of patient-derived high and low phosphatidylserine-exposing colorectal carcinoma cells in their interaction with anti-cancer peptides

Wilms

Andrä

2017

J. Pept. Sci.

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Current cancer treatment is frequently compromised by severe adverse effects on healthy cells and tissues as well as by the increasing burden of (multi-)drug resistances. Some representatives of small, amphipathic peptides known as host defense peptides possess the potential to overcome these limitations and to evolve as future anti-cancer therapeutics. Peptide NK-2, derived from porcine NK-lysin, was originally discovered due to its broad-spectrum antimicrobial activities. Today, also potent anti-cancer activity is proven and accompanied by low toxicity towards normal human cells. The molecular basis underlying this target selectivity remains rather elusive. Nevertheless, it is presumptive that preferential peptide interactions with surface factors non-abundant on healthy human cells play a key role. Here, we investigated the cytotoxicity of peptide NK-2 and structurally improved anti-cancer variants thereof against two patient-derived colorectal cancer cell lines, exposing high and low levels of phosphatidylserine on their cell surfaces, respectively. Concluding from a range of in vitro tests involving cellular as well as lipid vesicle-based methods, it is proposed that the magnitude of the accessible membrane surface charge is not a primarily decisive factor for selective peptide interactions. Instead, it is suggested that the level of membrane surface-exposed phosphatidylserine is of crucial importance for the activity of peptide NK-2 and enhanced variants thereof in terms of their cancer cell selectivity, the overall efficacy, as well as the underlying mode of action and kinetics. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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Antibacterial activity in human amniotic fluid: dependence on divalent cations

Cited by 10 publications

References 13 publications

Transcriptome Adaptation of Group B Streptococcus to Growth in Human Amniotic Fluid

Transcriptome Adaptation of Group B Streptococcus to Growth in Human Amniotic Fluid

Activity of the De Novo Engineered Antimicrobial Peptide WLBU2 against Pseudomonas aeruginosa in Human Serum and Whole Blood: Implications for Systemic Applications

Comparison of patient-derived high and low phosphatidylserine-exposing colorectal carcinoma cells in their interaction with anti-cancer peptides

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