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Dr. Dina Raafat
University Medicine Greifswald (Germany)

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0 Monoclonal Antibodies
0 Staphylococcus aureus
0 vaccine
0 host adaptation
0 Antibody response to infection

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Staphylococcus aureus
vaccine
Antibody response to infection
Monoclonal Antibodies

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Review
Published: 18 November 2020 in Toxins
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Pneumonia is an acute pulmonary infection associated with high mortality and an immense financial burden on healthcare systems. Staphylococcus aureus is an opportunistic pathogen capable of inducing S. aureus pneumonia (SAP), with some lineages also showing multidrug resistance. Given the high level of antibiotic resistance, much research has been focused on targeting S. aureus virulence factors, including toxins and biofilm-associated proteins, in an attempt to develop effective SAP therapeutics. Despite several promising leads, many hurdles still remain for S. aureus vaccine research. Here, we review the state-of-the-art SAP therapeutics, highlight their pitfalls, and discuss alternative approaches of potential significance and future perspectives.

ACS Style

Jelle Vlaeminck; Dina Raafat; Kristin Surmann; Leen Timbermont; Nicole Normann; Bret Sellman; Willem J. B. Van Wamel; Surbhi Malhotra-Kumar. Exploring Virulence Factors and Alternative Therapies against Staphylococcus aureus Pneumonia. Toxins 2020, 12, 721 .

AMA Style

Jelle Vlaeminck, Dina Raafat, Kristin Surmann, Leen Timbermont, Nicole Normann, Bret Sellman, Willem J. B. Van Wamel, Surbhi Malhotra-Kumar. Exploring Virulence Factors and Alternative Therapies against Staphylococcus aureus Pneumonia. Toxins. 2020; 12 (11):721.

Chicago/Turabian Style

Jelle Vlaeminck; Dina Raafat; Kristin Surmann; Leen Timbermont; Nicole Normann; Bret Sellman; Willem J. B. Van Wamel; Surbhi Malhotra-Kumar. 2020. "Exploring Virulence Factors and Alternative Therapies against Staphylococcus aureus Pneumonia." Toxins 12, no. 11: 721.

Review
Published: 25 September 2020 in International Journal of Molecular Sciences
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Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus infection. Major advances towards understanding the pathogenesis of S. aureus diseases have been made using conventional mouse models, i.e., by infecting naïve laboratory mice with human-adapted S.aureus strains. However, the failure to transfer certain results obtained in these murine systems to humans highlights the limitations of such models. Indeed, numerous S. aureus vaccine candidates showed promising results in conventional mouse models but failed to offer protection in human clinical trials. These limitations arise not only from the widely discussed physiological differences between mice and humans, but also from the lack of attention that is paid to the specific interactions of S. aureus with its respective host. For instance, animal-derived S. aureus lineages show a high degree of host tropism and carry a repertoire of host-specific virulence and immune evasion factors. Mouse-adapted S.aureus strains, humanized mice, and microbiome-optimized mice are promising approaches to overcome these limitations and could improve transferability of animal experiments to human trials in the future.

ACS Style

Daniel M. Mrochen; Liliane M. Fernandes De Oliveira; Dina Raafat; Silva Holtfreter. Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models. International Journal of Molecular Sciences 2020, 21, 7061 .

AMA Style

Daniel M. Mrochen, Liliane M. Fernandes De Oliveira, Dina Raafat, Silva Holtfreter. Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models. International Journal of Molecular Sciences. 2020; 21 (19):7061.

Chicago/Turabian Style

Daniel M. Mrochen; Liliane M. Fernandes De Oliveira; Dina Raafat; Silva Holtfreter. 2020. "Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models." International Journal of Molecular Sciences 21, no. 19: 7061.

Original research article
Published: 31 July 2020 in Frontiers in Immunology
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In murine abdominal sepsis by colon ascendens stent peritonitis (CASP), a strong increase in serum IgM and IgG antibodies was observed, which reached maximum values 14 days following sepsis induction. The specificity of this antibody response was studied in serum and at the single cell level using a broad panel of bacterial, sepsis-unrelated as well as self-antigens. Whereas an antibacterial IgM/IgG response was rarely observed, studies at the single-cell level revealed that IgM antibodies, in particular, were largely polyreactive. Interestingly, at least 16% of the IgM mAbs and 20% of the IgG mAbs derived from post-septic mice showed specificity for oxidation-specific epitopes (OSEs), which are known targets of the innate/adaptive immune response. This identifies those self-antigens as the main target of B cell responses in sepsis.

ACS Style

Oliver Nicolai; Christian Pötschke; Dina Raafat; Julia Van Der Linde; Sandra Quosdorf; Anna Laqua; Claus-Dieter Heidecke; Claudia Berek; Murthy N. Darisipudi; Christoph J. Binder; Barbara M. Bröker. Oxidation-Specific Epitopes (OSEs) Dominate the B Cell Response in Murine Polymicrobial Sepsis. Frontiers in Immunology 2020, 11, 1570 .

AMA Style

Oliver Nicolai, Christian Pötschke, Dina Raafat, Julia Van Der Linde, Sandra Quosdorf, Anna Laqua, Claus-Dieter Heidecke, Claudia Berek, Murthy N. Darisipudi, Christoph J. Binder, Barbara M. Bröker. Oxidation-Specific Epitopes (OSEs) Dominate the B Cell Response in Murine Polymicrobial Sepsis. Frontiers in Immunology. 2020; 11 ():1570.

Chicago/Turabian Style

Oliver Nicolai; Christian Pötschke; Dina Raafat; Julia Van Der Linde; Sandra Quosdorf; Anna Laqua; Claus-Dieter Heidecke; Claudia Berek; Murthy N. Darisipudi; Christoph J. Binder; Barbara M. Bröker. 2020. "Oxidation-Specific Epitopes (OSEs) Dominate the B Cell Response in Murine Polymicrobial Sepsis." Frontiers in Immunology 11, no. : 1570.

Original research article
Published: 30 April 2020 in Frontiers in Immunology
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Although antigen-specific priming of antibody responses is impaired during sepsis, there is nevertheless a strong increase in IgM and IgG serum concentrations. Using colon ascendens stent peritonitis (CASP), a mouse model of polymicrobial abdominal sepsis, we observed substantial increases in IgM as well as IgG of all subclasses, starting at day 3 and peaking 2 weeks after sepsis induction. The dominant source of antibody-secreting cells was by far the spleen, with a minor contribution of the mesenteric lymph nodes. Remarkably, sepsis induction in splenectomized mice did not change the dynamics of the serum IgM/IgG reaction, indicating that the marginal zone B cells, which almost exclusively reside in the spleen, are dispensable in such a setting. Hence, in systemic bacterial infection, the function of the spleen as dominant niche of antibody-producing cells can be compensated by extra-splenic B cell populations as well as other lymphoid organs. Depletion of CD4+ T cells did not affect the IgM response, while it impaired IgG generation of all subclasses with the exception of IgG3. Taken together, our data demonstrate that the robust class-switched antibody response in sepsis encompasses both T cell-dependent and -independent components.

ACS Style

Oliver Nicolai; Christian Pötschke; Katrin Schmoeckel; Murthy N. Darisipudi; Julia Van Der Linde; Dina Raafat; Barbara M. Bröker. Antibody Production in Murine Polymicrobial Sepsis—Kinetics and Key Players. Frontiers in Immunology 2020, 11, 1 .

AMA Style

Oliver Nicolai, Christian Pötschke, Katrin Schmoeckel, Murthy N. Darisipudi, Julia Van Der Linde, Dina Raafat, Barbara M. Bröker. Antibody Production in Murine Polymicrobial Sepsis—Kinetics and Key Players. Frontiers in Immunology. 2020; 11 ():1.

Chicago/Turabian Style

Oliver Nicolai; Christian Pötschke; Katrin Schmoeckel; Murthy N. Darisipudi; Julia Van Der Linde; Dina Raafat; Barbara M. Bröker. 2020. "Antibody Production in Murine Polymicrobial Sepsis—Kinetics and Key Players." Frontiers in Immunology 11, no. : 1.

Journal article
Published: 24 January 2020 in Toxins
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Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and laboratory rats were genotyped and profiled for antibiotic resistances and human-specific virulence genes. The nasal S. aureus carriage rate was higher among wild rats (23.4%) than laboratory rats (12.3%). Free-living wild rats were primarily colonized with isolates of clonal complex (CC) 49 and CC130 and maintained these strains even in husbandry. Moreover, upon livestock contact, CC398 isolates were acquired. In contrast, laboratory rats were colonized with many different S. aureus lineages—many of which are commonly found in humans. Five captive wild rats were colonized with CC398-MRSA. Moreover, a single CC30-MRSA and two CC130-MRSA were detected in free-living or captive wild rats. Rat-derived S. aureus isolates rarely harbored the phage-carried immune evasion gene cluster or superantigen genes, suggesting long-term adaptation to their host. Taken together, our study revealed a natural S. aureus population in wild rats, as well as a colonization pressure on wild and laboratory rats by exposure to livestock- and human-associated S. aureus, respectively.

ACS Style

Dina Raafat; Daniel M. Mrochen; Fawaz Al’Sholui; Elisa Heuser; René Ryll; Kathleen R. Pritchett-Corning; Jens Jacob; Bernd Walther; Franz-Rainer Matuschka; Dania Richter; Uta Westerhüs; Jiri Pikula; Jens Van Den Brandt; Werner Nicklas; Stefan Monecke; Birgit Strommenger; Sarah Van Alen; Karsten Becker; Rainer G. Ulrich; Silva Holtfreter. Molecular Epidemiology of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Wild, Captive and Laboratory Rats: Effect of Habitat on the Nasal S. aureus Population. Toxins 2020, 12, 80 .

AMA Style

Dina Raafat, Daniel M. Mrochen, Fawaz Al’Sholui, Elisa Heuser, René Ryll, Kathleen R. Pritchett-Corning, Jens Jacob, Bernd Walther, Franz-Rainer Matuschka, Dania Richter, Uta Westerhüs, Jiri Pikula, Jens Van Den Brandt, Werner Nicklas, Stefan Monecke, Birgit Strommenger, Sarah Van Alen, Karsten Becker, Rainer G. Ulrich, Silva Holtfreter. Molecular Epidemiology of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Wild, Captive and Laboratory Rats: Effect of Habitat on the Nasal S. aureus Population. Toxins. 2020; 12 (2):80.

Chicago/Turabian Style

Dina Raafat; Daniel M. Mrochen; Fawaz Al’Sholui; Elisa Heuser; René Ryll; Kathleen R. Pritchett-Corning; Jens Jacob; Bernd Walther; Franz-Rainer Matuschka; Dania Richter; Uta Westerhüs; Jiri Pikula; Jens Van Den Brandt; Werner Nicklas; Stefan Monecke; Birgit Strommenger; Sarah Van Alen; Karsten Becker; Rainer G. Ulrich; Silva Holtfreter. 2020. "Molecular Epidemiology of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Wild, Captive and Laboratory Rats: Effect of Habitat on the Nasal S. aureus Population." Toxins 12, no. 2: 80.

Review
Published: 01 April 2019 in Trends in Microbiology
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Staphylococcus aureus (S. aureus) is a notorious pathogen and one of the most frequent causes of biofilm-related infections. The treatment of S. aureus biofilms is hampered by the ability of the biofilm structure to shield bacteria from antibiotics as well as the host's immune system. Therefore, new preventive and/or therapeutic interventions, including the use of antibody-based approaches, are urgently required. In this review, we describe the mechanisms by which anti-S. aureus antibodies can help in combating biofilms, including an up-to-date overview of monoclonal antibodies currently in clinical trials. Moreover, we highlight ongoing efforts in passive vaccination against S. aureus biofilm infections, with special emphasis on promising targets, and finally indicate the direction into which future research could be heading.

ACS Style

Dina Raafat; Michael Otto; Kevin Reppschläger; Jawad Iqbal; Silva Holtfreter. Fighting Staphylococcus aureus Biofilms with Monoclonal Antibodies. Trends in Microbiology 2019, 27, 303 -322.

AMA Style

Dina Raafat, Michael Otto, Kevin Reppschläger, Jawad Iqbal, Silva Holtfreter. Fighting Staphylococcus aureus Biofilms with Monoclonal Antibodies. Trends in Microbiology. 2019; 27 (4):303-322.

Chicago/Turabian Style

Dina Raafat; Michael Otto; Kevin Reppschläger; Jawad Iqbal; Silva Holtfreter. 2019. "Fighting Staphylococcus aureus Biofilms with Monoclonal Antibodies." Trends in Microbiology 27, no. 4: 303-322.

Journal article
Published: 01 February 2017 in Carbohydrate Polymers
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The bacterial cell envelope is believed to be a principal target for initiating the staphylocidal pathway of chitosan. The present study was therefore designed to investigate possible changes in cell surface phenotypes related to the in vitro chitosan resistance development in the laboratory strain S. aureus SG511-Berlin. Following a serial passage experiment, a stable chitosan-resistant variant (CRV) was identified, exhibiting >50-fold reduction in its sensitivity towards chitosan. Our analyses of the CRV identified phenotypic and genotypic features that readily distinguished it from its chitosan-susceptible parental strain, including: (i) a lower overall negative cell surface charge; (ii) cross-resistance to a number of antimicrobial agents; (iii) major alterations in cell envelope structure, cellular bioenergetics and metabolism (based on transcriptional profiling); and (iv) a repaired sensor histidine kinase GraS. Our data therefore suggest a close nexus between changes in cell envelope properties with the in vitro chitosan-resistant phenotype in S. aureus SG511-Berlin.

ACS Style

Dina Raafat; Nicole Leib; Miriam Wilmes; Patrice François; Jacques Schrenzel; Hans-Georg Sahl. Development of in vitro resistance to chitosan is related to changes in cell envelope structure of Staphylococcus aureus. Carbohydrate Polymers 2017, 157, 146 -155.

AMA Style

Dina Raafat, Nicole Leib, Miriam Wilmes, Patrice François, Jacques Schrenzel, Hans-Georg Sahl. Development of in vitro resistance to chitosan is related to changes in cell envelope structure of Staphylococcus aureus. Carbohydrate Polymers. 2017; 157 ():146-155.

Chicago/Turabian Style

Dina Raafat; Nicole Leib; Miriam Wilmes; Patrice François; Jacques Schrenzel; Hans-Georg Sahl. 2017. "Development of in vitro resistance to chitosan is related to changes in cell envelope structure of Staphylococcus aureus." Carbohydrate Polymers 157, no. : 146-155.

Comparative study
Published: 09 December 2015 in BMC Microbiology
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Microbial contamination of pharmaceuticals poses a great problem to the pharmaceutical manufacturing process, especially from a medical as well as an economic point of view. Depending upon the product and its intended use, the identification of isolates should not merely be limited to the United States Pharmacopeia (USP) indicator organisms. Eighty-five pre-used non-sterile pharmaceuticals collected from random consumers in Egypt were examined for the eventual presence of bacterial contaminants. Forty-one bacterial contaminants were isolated from 31 of the tested preparations. These isolates were subjected to biochemical identification by both conventional tests as well as API kits, which were sufficient for the accurate identification of only 11 out of the 41 bacterial contaminants (26.8 %) to the species level. The remaining isolates were inconclusively identified or showed contradictory results after using both biochemical methods. Using molecular methods, 24 isolates (58.5 %) were successfully identified to the species level. Moreover, polymerase chain reaction (PCR) assays were compared to standard biochemical methods in the detection of pharmacopoeial bacterial indicators in artificially-contaminated pharmaceutical samples. PCR-based methods proved to be superior regarding speed, cost-effectiveness and sensitivity. Therefore, pharmaceutical manufacturers would be advised to adopt PCR-based methods in the microbiological quality testing of pharmaceuticals in the future.

ACS Style

Hend Zeitoun; Mervat Kassem; Dina Raafat; Hamida AbouShlieb; Nourhan Fanaki. Microbiological testing of pharmaceuticals and cosmetics in Egypt. BMC Microbiology 2015, 15, 1 -13.

AMA Style

Hend Zeitoun, Mervat Kassem, Dina Raafat, Hamida AbouShlieb, Nourhan Fanaki. Microbiological testing of pharmaceuticals and cosmetics in Egypt. BMC Microbiology. 2015; 15 (1):1-13.

Chicago/Turabian Style

Hend Zeitoun; Mervat Kassem; Dina Raafat; Hamida AbouShlieb; Nourhan Fanaki. 2015. "Microbiological testing of pharmaceuticals and cosmetics in Egypt." BMC Microbiology 15, no. 1: 1-13.

Journal article
Published: 01 December 2015 in International Journal of Nanomedicine
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Green synthesis of silver nanoparticles using cranberry powder aqueous extract: characterization and antimicrobial properties Asmaa A Ashour,1 Dina Raafat,2 Hanan M El-Gowelli,3 Amal H El-Kamel1 1Department of Pharmaceutics, 2Department of Pharmaceutical Microbiology, 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Background: The growing threat of microbial resistance against traditional antibiotics has prompted the development of several antimicrobial nanoparticles (NPs), including silver NPs (AgNPs). In this article, a simple and eco-friendly method for the synthesis of AgNPs using the cranberry powder aqueous extract is reported.Materials and methods: Cranberry powder aqueous extracts (0.2%, 0.5%, and 0.8% w/v) were allowed to interact for 24 hours with a silver nitrate solution (10 mM) at 30°C at a ratio of 1:10. The formation of AgNPs was confirmed by ultraviolet-visible spectroscopy and their concentrations were determined using atomic absorption spectroscopy. The prepared NPs were evaluated by transmission electron microscopy, measurement of ζ-potential, and Fourier-transform infrared spectroscopy. The in vitro antimicrobial properties of AgNPs were then investigated against several microbial strains. Finally, in vivo appraisal of both wound-healing and antimicrobial properties of either plain AgNPs (prepared using 0.2% extract) or AgNP-Pluronic F-127 gel was conducted in a rat model after induction of a Staphylococcus aureus ATCC 6538P wound infection.Results: The formation of AgNPs was confirmed by ultraviolet-visible spectroscopy, where a surface-plasmon resonance absorption peak was observed between 432 and 438 nm. Both size and concentration of the formed AgNPs increased with increasing concentration of the extracts. The developed NPs were stable, almost spherical, and polydisperse, with a size range of 1.4–8.6 nm. The negative ζ-potential values, as well as Fourier-transform infrared spectroscopy analysis, indicated the presence of a capping agent adsorbed onto the surface of the particles. In vitro antimicrobial evaluation revealed a size-dependent activity of the AgNPs against the tested organisms. Finally, AgNPs prepared using 0.2% extract exhibited a substantial in vivo healing potential for full-thickness excision wounds in rats.Conclusion: AgNPs were successfully synthesized from a silver nitrate solution through a simple green route, using cranberry powder aqueous extract as a reducing as well as capping agent. Keywords: cranberry, silver nanoparticles, antimicrobial properties, wound healing

ACS Style

Amal El-Kamel; Asmaa Ashour; Dina Raafat; Hanan El-Goweily. Green synthesis of silver nanoparticles using cranberry powder aqueous extract: characterization and antimicrobial properties. International Journal of Nanomedicine 2015, ume 10, 7207 -7221.

AMA Style

Amal El-Kamel, Asmaa Ashour, Dina Raafat, Hanan El-Goweily. Green synthesis of silver nanoparticles using cranberry powder aqueous extract: characterization and antimicrobial properties. International Journal of Nanomedicine. 2015; ume 10 ():7207-7221.

Chicago/Turabian Style

Amal El-Kamel; Asmaa Ashour; Dina Raafat; Hanan El-Goweily. 2015. "Green synthesis of silver nanoparticles using cranberry powder aqueous extract: characterization and antimicrobial properties." International Journal of Nanomedicine ume 10, no. : 7207-7221.

Review
Published: 13 January 2009 in Microbial Biotechnology
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Chitosan, an aminopolysaccharide biopolymer, has a unique chemical structure as a linear polycation with a high charge density, reactive hydroxyl and amino groups as well as extensive hydrogen bonding. It displays excellent biocompatibility, physical stability and processability. The term ‘chitosan’ describes a heterogenous group of polymers combining a group of physicochemical and biological characteristics, which allow for a wide scope of applications that are both fascinating and as yet uncharted. The increased awareness of the potentials and industrial value of this biopolymer lead to its utilization in many applications of technical interest, and increasingly in the biomedical arena. Although not primarily used as an antimicrobial agent, its utility as an ingredient in both food and pharmaceutical formulations lately gained more interest, when a scientific understanding of at least some of the pharmacological activities of this versatile carbohydrate began to evolve. However, understanding the various factors that affect its antimicrobial activity has become a key issue for a better usage and a more efficient optimization of chitosan formulations. Moreover, the use of chitosan in antimicrobial systems should be based on sufficient knowledge of the complex mechanisms of its antimicrobial mode of action, which in turn would help to arrive at an appreciation of its entire antimicrobial potential.

ACS Style

Dina Raafat; Hans-Georg Sahl. Chitosan and its antimicrobial potential - a critical literature survey. Microbial Biotechnology 2009, 2, 186 -201.

AMA Style

Dina Raafat, Hans-Georg Sahl. Chitosan and its antimicrobial potential - a critical literature survey. Microbial Biotechnology. 2009; 2 (2):186-201.

Chicago/Turabian Style

Dina Raafat; Hans-Georg Sahl. 2009. "Chitosan and its antimicrobial potential - a critical literature survey." Microbial Biotechnology 2, no. 2: 186-201.

Journal article
Published: 15 June 2008 in Applied and Environmental Microbiology
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Chitosan is a polysaccharide biopolymer that combines a unique set of versatile physicochemical and biological characteristics which allow for a wide range of applications. Although its antimicrobial activity is well documented, its mode of action has hitherto remained only vaguely defined. In this work we investigated the antimicrobial mode of action of chitosan using a combination of approaches, including in vitro assays, killing kinetics, cellular leakage measurements, membrane potential estimations, and electron microscopy, in addition to transcriptional response analysis. Chitosan, whose antimicrobial activity was influenced by several factors, exhibited a dose-dependent growth-inhibitory effect. A simultaneous permeabilization of the cell membrane to small cellular components, coupled to a significant membrane depolarization, was detected. A concomitant interference with cell wall biosynthesis was not observed. Chitosan treatment of Staphylococcus simulans 22 cells did not give rise to cell wall lysis; the cell membrane also remained intact. Analysis of transcriptional response data revealed that chitosan treatment leads to multiple changes in the expression profiles of Staphylococcus aureus SG511 genes involved in the regulation of stress and autolysis, as well as genes associated with energy metabolism. Finally, a possible mechanism for chitosan's activity is postulated. Although we contend that there might not be a single classical target that would explain chitosan's antimicrobial action, we speculate that binding of chitosan to teichoic acids, coupled with a potential extraction of membrane lipids (predominantly lipoteichoic acid) results in a sequence of events, ultimately leading to bacterial death.

ACS Style

Dina Raafat; Kristine von Bargen; Albert Haas; Hans-Georg Sahl. Insights into the Mode of Action of Chitosan as an Antibacterial Compound. Applied and Environmental Microbiology 2008, 74, 3764 -3773.

AMA Style

Dina Raafat, Kristine von Bargen, Albert Haas, Hans-Georg Sahl. Insights into the Mode of Action of Chitosan as an Antibacterial Compound. Applied and Environmental Microbiology. 2008; 74 (12):3764-3773.

Chicago/Turabian Style

Dina Raafat; Kristine von Bargen; Albert Haas; Hans-Georg Sahl. 2008. "Insights into the Mode of Action of Chitosan as an Antibacterial Compound." Applied and Environmental Microbiology 74, no. 12: 3764-3773.