<i>Burkholderia</i>
            Is Highly Resistant to Human Beta-Defensin 3

Sahly, Hany; Schubert, Sabine; Harder, Jürgen; Rautenberg, Peter; Ullmann, U.; Schröder, Jens-Michael; Podschun, Rainer

doi:10.1128/aac.47.5.1739-1741.2003

Cited by 68 publications

(66 citation statements)

References 27 publications

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“…Since previous studies have demonstrated that Burkholderia species are very resistant to b-defensins and other antimicrobial peptides (Baird et al, 1999;Burtnick & Woods, 1999;Loutet et al, 2006;Sahly et al, 2003), it is possible that mutations in zmpA and/or zmpB are insufficient to result in increased susceptibility to the antimicrobial activity of these defensins, due to myriad resistance mechanisms. It is also possible that the cleavage products generated by ZmpA or ZmpB retain antimicrobial activity.…”

Section: Resultsmentioning

confidence: 99%

Burkholderia cenocepacia zinc metalloproteases influence resistance to antimicrobial peptides

Kooi

Sokol

2009

Microbiology

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Burkholderia cenocepacia secretes two zinc-dependent metalloproteases, designated ZmpA and ZmpB. Previously, ZmpA and ZmpB have been shown to cleave several proteins important in host defence. In this study, the ability of ZmpA and ZmpB to digest and inactivate antimicrobial peptides involved in innate immunity was examined. ZmpB but not ZmpA cleaved β-defensin-1. ZmpA but not ZmpB cleaved the cathelicidin LL-37. Both enzymes cleaved elafin and secretory leukocyte inhibitor, which are antimicrobial peptides as well as neutrophil elastase inhibitors. Both ZmpA and ZmpB cleaved protamine, a fish antimicrobial peptide, and a zmpA zmpB mutant was more sensitive to protamine killing than the parental strain. ZmpA or ZmpB cleavage of elafin inactivated its anti-protease activity. The effect of ZmpA and ZmpB on the neutrophil proteases elastase and cathepsin G was also examined but neither enzyme was active against these host proteases. These studies suggest that ZmpA and ZmpB may influence the resistance of B. cenocepacia to host antimicrobial peptides as well as alter the host protease/anti-protease balance in chronic respiratory infections.

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Section: Resultsmentioning

confidence: 99%

Burkholderia cenocepacia zinc metalloproteases influence resistance to antimicrobial peptides

Kooi

Sokol

2009

Microbiology

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“…Determination of Antimicrobial Activity and Salt ToleranceThe antimicrobial activity of theromacin and neuromacin was investigated as described previously (22). Hydramacin-1 4 served as reference molecule and was also measured in parallel.…”

Section: Methodsmentioning

confidence: 99%

“…Arbitrarily, a strain was defined as susceptible to a peptide if it had an MBC or LD 90 of Յ12.5 g/ml, as intermediately susceptible if it had an MBC or LD 90 of Ͼ12.5-100 g/ml, or as resistant if it had an MBC or LD 90 of Ͼ100 g/ml as described elsewhere (22).…”

Section: Methodsmentioning

confidence: 99%

Macin Family of Antimicrobial Proteins Combines Antimicrobial and Nerve Repair Activities

Jung¹,

Sönnichsen²,

Hung³

et al. 2012

Journal of Biological Chemistry

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Background: Antimicrobial macin proteins aggregate bacteria and exert nerve repair activities. Results: Structures of theromacin and neuromacin were elucidated. Nerve repair activities and antimicrobial activities of macins were investigated. Conclusion: Theromacin induces the nerve repair capacity of leech plasma. Macins seem to be proliferation factors. Significance: The extended magnitude of macin activities demands reconsidering their potential biological impact on nerve repair/neurons in their hosts.

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“…Li et al, showed that exposure to sub-inhibitory concentra-287 tions of hBD-3 resulted in a significant upregulation of the expression of the dlt operon, and a 288 subsequent increase in D-alanylation of teichoic acids in S. epidermidis [30]. A comparable 289 mechanism with a change in the bacterial surface charge to resist human beta-defensins is 290 also discussed for Gram-negative bacteria [31]. Therefore, a correlation between the mecha 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Reichel et al Bacterial response to human β-Defensin-3 after chlorhexidine exposure 15 nism of bacteria to circumvent the natural host defence of the skin caused by AMPs and the 292 mechanism for resistance to cationic antimicrobials, e.g.…”

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confidence: 98%

Skin bacteria after chlorhexidine exposure—is there a difference in response to human β-Defensin-3?

Reichel

Heisig

et al. 2010

Eur J Clin Microbiol Infect Dis

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Purpose:We investigated whether exposure to sub-lethal concentrations of chlorhexidine digluconate (CH) changed the response of 5 Staphylococcus spp. to human β-Defensin-3. Methods:The change in response for each strain was determined in-vitro with time-kill-experiments in suspension by comparing the mean log10-reduction caused by hBD-3 at 1.5 and 3 h in exposed and non-exposed bacteria. Identity of staphylococcal species was verified by DNA sequence homology in the gyrA genes in comparison with reference strains.Results: Baseline sub-lethal concentrations allowing visible bacterial growth were between 0.0625 and 0.25 μg/ml. Sub-lethal CH concentrations increased within 3 days in two isolates. For Staphylococcus capitis 19/2, CH-exposed cells were less susceptible to 0.5 μg/ml hBD-3 (log10-reduction 0.78 versus 2.06 at 1.5 h; p <0.001; t-test). For Staphylococcus aureus, however, CH-exposed cells were more susceptible to 1 μg/ml hBD-3. The observed changes between CH-exposed and non-exposed cells did not indicate a general trend in response to hBD-3. Conclusions:Overall, we found no consistent evidence that 3 days of exposure to CHG changed the response of 5 Staphylococcus spp. to hBD-3. The use of CHG for skin antisepsis is, based on our data, unlikely to change the natural defence activity of hBD-3.Response to Reviewers: REVIEWER #1:Major points:Reviewer comment: Human beta-defensin-3 is a very sticky peptide. To minimize losses, cationic antimicrobial peptides are usually dissolved in weakly acidic solvents. The authors used water, which could influence losses of the peptide and thus might influence its concentration in the remaining solution.Response: We were aware that some studies were published with hBD-3 using acetic acid for dissolving the peptide, but the manufacturer (RELIATech) confirmed that their hBD-3 should be reconstituted in water, that it can also be diluted in water and that the use of water will not change the activity of the peptide which was used for the test. That was the reason why we used water (pH-value between 6.5 and 6.8).Reviewer comment: Did the authors pool the beta-defensin-3? If yes, did they use the material at exactly identical conditions (e.g. storage at ambient temperature or in the refrigerator after thawing). If not, one would expect variable results.Response: Whenever necessary, we pooled aliquots of the diluted peptide after thawing. We did not pool different batches because we only used one batch of the peptide. Nevertheless, we used cooled metal blocks for the storage of the peptide after thawing to ensure that the con-ditions did not change between tests.The part in the Methods section of the manuscript was amended to clarify the questions of the reviewer.Reviewer comment: Could the authors reproduce in independent experiments (with another peptide sample) the results they found in the four cases where hBD-3 killed significantly fewer bacteria?Response: It is a very interesting question if the decrease of the sensitivity of the strain to hBD-3 could also be ...

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Burkholderia Is Highly Resistant to Human Beta-Defensin 3

Cited by 68 publications

References 27 publications

Burkholderia cenocepacia zinc metalloproteases influence resistance to antimicrobial peptides

Burkholderia cenocepacia zinc metalloproteases influence resistance to antimicrobial peptides

Macin Family of Antimicrobial Proteins Combines Antimicrobial and Nerve Repair Activities

Skin bacteria after chlorhexidine exposure—is there a difference in response to human β-Defensin-3?

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