Host defence against Staphylococcus aureus biofilms infection: Phagocytosis of biofilms by polymorphonuclear neutrophils (PMN)

Günther, Frank; Wabnitz, Guido H.; Stroh, Petra; Prior, Birgit; Obst, Ursula; Samstag, Yvonne; Wagner, C.; Hänsch, Gertrud Maria

doi:10.1016/j.molimm.2009.01.020

Cited by 122 publications

(89 citation statements)

References 30 publications

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“…5; see also Movies S5 and S6 in the supplemental material). Günther and coworkers have shown phagocytosis of S. aureus biofilms under static conditions (35), but to our knowledge, this is the first demonstration of biofilm opsonophagocytosis under conditions of shear flow. Since staphylococcal biofilms leading to CLABSI are bathed in flowing blood, the recruitment of neutrophils in our model is highly relevant to the in vivo infection: circulating neutrophils must adhere strongly to avoid being washed away by shear flow forces.…”

Section: Discussionmentioning

confidence: 69%

Antibodies to PhnD Inhibit Staphylococcal Biofilms

et al. 2014

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Biofilm formation on central lines or peripheral catheters is a serious threat to patient well-being. Contaminated vascular devices can act as a nidus for bloodstream infection and systemic pathogen dissemination. Staphylococcal biofilms are the most common cause of central-line-associated bloodstream infections, and antibiotic resistance makes them difficult to treat. As an alternative to antibiotic intervention, we sought to identify anti-staphylococcal biofilm targets for the development of a vaccine or antibody prophylactic. A screening strategy was devised using a microfluidic system to test antibody-mediated biofilm inhibition under biologically relevant conditions of shear flow. Affinity-purified polyclonal antibodies to target antigen PhnD inhibited both Staphylococcus epidermidis and S. aureus biofilms. PhnD-specific antibodies blocked biofilm development at the initial attachment and aggregation stages, and deletion of phnD inhibited normal biofilm formation. We further adapted our microfluidic biofilm system to monitor the interaction of human neutrophils with staphylococcal biofilms and demonstrated that PhnD-specific antibodies also serve as opsonins to enhance neutrophil binding, motility, and biofilm engulfment. These data support the identification of PhnD as a lead target for biofilm intervention strategies performed either by vaccination or through passive administration of antibodies.

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Section: Discussionmentioning

confidence: 69%

Antibodies to PhnD Inhibit Staphylococcal Biofilms

et al. 2014

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“…In vitro studies lead to a more or less similar conclusion: Leid et al (Leid et al 2002) reported an inefficient phagocytosis of Staphyoloccocus aureus by leukocytes, presumably monocytes, and Jesaitis et al (Jesaitis et al 2002) described that neutrophils were immobilised on biofilms of Pseudomonas aeruginosa, and thus their cytotoxic capacity was limited (Jesaitis et al 2002). More recently, we showed that bacteria in biofilms are not entirely protected against host defence mechanisms, but that the maturation state of the biofilm greatly influences the efficiency of phagocytosis (Guenther et al 2009a). Moreover, biofilms of different species differed greatly with regard to their sensitivity towards neutrophils (Guenther et al 2009b).…”

Section: Introductionmentioning

confidence: 69%

Host defence against Staphylococcus aureus biofilms by polymorphonuclear neutrophils: Oxygen radical production but not phagocytosis depends on opsonisation with immunoglobulin G

et al. 2011

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“…Biofilm maturation is another point that can impact eradication results. "Young" biofilms were more sensitive to attack by neutrophils than were mature biofilms (57). Our testing of PMB and GS activity against pregrown biofilms showed that a strong inhibition of respiration occurred only when biofilms were treated with PMB and GS in combination, but not if the peptides were applied separately.…”

Section: Fig 5 Pmb-and-gs Combination Treatment Of Pregrown P Aerugimentioning

confidence: 77%

Synergistic Effect of Membrane-Active Peptides Polymyxin B and Gramicidin S on Multidrug-Resistant Strains and Biofilms of Pseudomonas aeruginosa

Berditsch

Jäger

Strempel

et al. 2015

Antimicrob Agents Chemother

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Multidrug-resistant Pseudomonas aeruginosa is a major cause of severe hospital-acquired infections. Currently, polymyxin B (PMB) is a last-resort antibiotic for the treatment of infections caused by Gram-negative bacteria, despite its undesirable side effects. The delivery of drug combinations has been shown to reduce the required therapeutic doses of antibacterial agents and thereby their toxicity if a synergistic effect is present. In this study, we investigated the synergy between two cyclic antimicrobial peptides, PMB and gramicidin S (GS), against different P. aeruginosa isolates, using a quantitative checkerboard assay with resazurin as a growth indicator. Among the 28 strains that we studied, 20 strains showed a distinct synergistic effect, represented by a fractional inhibitory concentration index (FICI) of <0.5. Remarkably, several clinical P. aeruginosa isolates that grew as smallcolony variants revealed a nonsynergistic effect, as indicated by FICIs between >0.5 and <0.70. In addition to inhibiting the growth of planktonic bacteria, the peptide combinations significantly decreased static biofilm growth compared with treatment with the individual peptides. There was also a faster and more prolonged effect when the combination of PMB and GS was used compared with single-peptide treatments on the metabolic activity of pregrown biofilms. The results of the present study define a synergistic interaction between two cyclic membrane-active peptides toward 17 multidrug-resistant P. aeruginosa and biofilms of P. aeruginosa strain PAO1. Thus, the application of PMB and GS in combination is a promising option for a topical medication and in the prevention of acute and chronic infections caused by multidrug-resistant or biofilm-forming P. aeruginosa. Pathogenic Gram-negative Pseudomonas aeruginosa possesses both intrinsic and adaptive resistance toward many currently available antibiotics and causes infections that are effectively untreatable (1-3). P. aeruginosa "superbugs" are resistant to fluoroquinolones, expanded-spectrum cephalosporins, carbapenems, aminoglycosides, and in a few cases, even polymyxins, a last-resort class of antibiotics used to treat P. aeruginosa infections (4-7). One important mechanism for the intrinsic antibiotic resistance of Gram-negative pathogens, especially multidrug-resistant (MDR) P. aeruginosa clinical isolates, is their ability to efflux antibacterial agents via tripartite efflux pumps located in the inner and outer membranes, a mechanism that limits the access of the drug to intracellular targets (8). However, the overexpression of the P. aeruginosa efflux pump protein MexAB was unable to confer resistance to the host defense peptides (HDPs) cathelicidin LL-37 and defensins (9). One way in which pathogens acquire adaptive resistance to positively charged antimicrobial peptides is to modify lipid A by substitution with aminoarabinose (6). The emergence of drug-resistant P. aeruginosa strains, which exhibit increased MICs even for polymyxin B (PMB) (10), requires the development...

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Host defence against Staphylococcus aureus biofilms infection: Phagocytosis of biofilms by polymorphonuclear neutrophils (PMN)

Cited by 122 publications

References 30 publications

Antibodies to PhnD Inhibit Staphylococcal Biofilms

Antibodies to PhnD Inhibit Staphylococcal Biofilms

Host defence against Staphylococcus aureus biofilms by polymorphonuclear neutrophils: Oxygen radical production but not phagocytosis depends on opsonisation with immunoglobulin G

Synergistic Effect of Membrane-Active Peptides Polymyxin B and Gramicidin S on Multidrug-Resistant Strains and Biofilms of Pseudomonas aeruginosa

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