The Bacterial Peptide <i>N</i>-Formyl-Met-Leu-Phe Inhibits Killing of <i>Staphylococcus epidermidis</i> by Human Neutrophils in Fibrin Gels

Li, Yongmei; Loike, John D.; Ember, Julia A.; Cleary, P. Patrick; Lu, Emily; Budhu, Sadna; Cao, Long; Silverstein, Samuel C.

doi:10.4049/jimmunol.168.2.816

Cited by 15 publications

(18 citation statements)

References 56 publications

(58 reference statements)

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“…Previous studies (13) showed that incubation of S. epidermidis H753 with human serum opsonized these bacteria with IgG and the C3 component of complement, and that opsonization with both IgG and C3 is required for killing in suspension by neutrophils. We used this system to assess whether killing of S. epidermidis by neutrophils depends on the neutrophil concentration or the ratio of neutrophils to bacteria.…”

Section: Resultsmentioning

confidence: 99%

A critical concentration of neutrophils is required for effective bacterial killing in suspension

Karlin

Loike

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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We have examined the effect of neutrophil concentration on killing of a clinical isolate of Staphylococcus epidermidis. Human neutrophils at concentrations varying from 10 5 to 10 7 per ml were mixed in suspension with S. epidermidis at concentrations varying from 10 3 to 10 8 colony-forming units͞ml, and the concentration of viable bacteria was assayed after various times at 37°C. The rate of bacterial killing depended on the concentration of neutrophils and not on the ratio of neutrophils to bacteria. Below a critical concentration of neutrophils, bacteria growth was greater than neutrophil killing of bacteria even when the ratio of neutrophils to bacteria was 100:1. We fitted the time course of bacterial concentration and its dependence on neutrophil concentration with an exponential function, the exponent of which is (؊kp ؉ g)t, where k is the second-order rate constant for bacterial killing, p is the neutrophil concentration, g is the first-order rate constant for bacterial growth, and t is time. We found that k Ϸ 2 ؋ 10 ؊8 ml per neutrophil per min, and g Ϸ 8 ؋ 10 ؊3 ͞min. Only when p is greater than g͞k, which we call the critical neutrophil concentration, does the bacterial concentration fall. Under optimal assay conditions, the critical neutrophil concentration was 3-4 ؋ 10 5 per ml, a value very close to that (<5 ؋ 10 5 per ml) known to predispose humans to bacterial and fungal infections.

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Section: Resultsmentioning

confidence: 99%

A critical concentration of neutrophils is required for effective bacterial killing in suspension

Karlin

Loike

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

110

126

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“…Complement component C5a is important for rapid neutrophil recruitment to the sites of streptococcal infection [11] and is required for neutrophil-mediated bacterial killing [12]. C5a peptidase (SCPA), a surface virulence factor, is highly conserved among GAS serotypes.…”

Section: Introductionmentioning

confidence: 99%

Co-Activation of Th17 and Antibody Responses Provides Efficient Protection against Mucosal Infection by Group A Streptococcus

Chen

et al. 2016

PLoS ONE

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Conserved protein antigens among serotypes of group A Streptococcus pyogenes (GAS) have been focused for vaccine development because of the diversity of GAS serotypes and risks of autoimmunity post-GAS infection. Precise delineation of protective immune response to each of GAS antigens is critical for vaccine efficacy and safety. We recently reported that immunization with SrtA of GAS provides Th17-dependent clearance of heterologous serotypes of GAS in NALT. SCPA is a surface virulence molecule of GAS and known to induce antibody-mediated protection against GAS. We hypothesized that co-immunization with SrtA and SCPA would provide more efficient protection by eliciting combined Th17 and antibody responses. The present study showed that mice that were intranasally co-immunized with SrtA/SCPA cleared GAS more efficiently than the mice that were immunized with either SrtA or SCPA individually, and as efficient as the mice that experienced repeated GAS infections. The co-immunization induced Th17 and robust SCPA antibody responses, accompanied by a rapid influx of neutrophils and high myeloperoxidase activity in NALT, suggesting that simultaneous induction of mucosal Th17 and neutralizing antibody responses offers more effective GAS elimination through rapid infiltration and activation of neutrophils. Moreover, Th17 response was strongly induced in mice that experienced repeated GAS-infection and maintained at a high level even after the bacteria were cleared; whereas, it was moderately induced and promptly returned to baseline following bacterial elimination in SrtA/SCPA co-immunized mice. Additional results showed that the survival rate of systemic challenge was significantly higher in infection experienced than in co-immunized mice, indicating that more immune elements are required for protection against systemic than mucosal GAS infection.

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“…Following two serial 10-fold dilutions in sterile water, 50 μL of the sonicated solution was added to bacterial TSB agar plates and incubated at 37°C. The bacterial colonies that formed were counted after 48 hour [14], [15]. At these dilutions, control plates incubated in the absence of neutrophils usually contained approximately 2,000 colonies, or 10 7 bacteria per disc.…”

Section: Methodsmentioning

confidence: 99%

Surface Acoustic Waves Enhance Neutrophil Killing of Bacteria

et al. 2013

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Biofilms are structured communities of bacteria that play a major role in the pathogenicity of bacteria and are the leading cause of antibiotic resistant bacterial infections on indwelling catheters and medical prosthetic devices. Failure to resolve these biofilm infections may necessitate the surgical removal of the prosthetic device which can be debilitating and costly. Recent studies have shown that application of surface acoustic waves to catheter surfaces can reduce the incidence of infections by a mechanism that has not yet been clarified. We report here the effects of surface acoustic waves (SAW) on the capacity of human neutrophils to eradicate S. epidermidis bacteria in a planktonic state and within biofilms. Utilizing a novel fibrin gel system that mimics a tissue-like environment, we show that SAW, at an intensity of 0.3 mW/cm2, significantly enhances human neutrophil killing of S. epidermidis in a planktonic state and within biofilms by enhancing human neutrophil chemotaxis in response to chemoattractants. In addition, we show that the integrin CD18 plays a significant role in the killing enhancement observed in applying SAW. We propose from out data that this integrin may serve as mechanoreceptor for surface acoustic waves enhancing neutrophil chemotaxis and killing of bacteria.

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The Bacterial Peptide N-Formyl-Met-Leu-Phe Inhibits Killing of Staphylococcus epidermidis by Human Neutrophils in Fibrin Gels

Cited by 15 publications

References 56 publications

A critical concentration of neutrophils is required for effective bacterial killing in suspension

A critical concentration of neutrophils is required for effective bacterial killing in suspension

Co-Activation of Th17 and Antibody Responses Provides Efficient Protection against Mucosal Infection by Group A Streptococcus

Surface Acoustic Waves Enhance Neutrophil Killing of Bacteria

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