Publications by authors named "Jeff G Leid"

34 Publications

Development of a Novel and Rapid Antibody-Based Diagnostic for Chronic Staphylococcus aureus Infections Based on Biofilm Antigens.

J Clin Microbiol 2020 04 23;58(5). Epub 2020 Apr 23.

Northern Arizona University, Flagstaff, Arizona, USA.

Prosthetic joint infections are difficult to diagnose and treat due to biofilm formation by the causative pathogens. Pathogen identification relies on microbial culture that requires days to weeks, and in the case of chronic biofilm infections, lacks sensitivity. Diagnosis of infection is often delayed past the point of effective treatment such that only the removal of the implant is curative. Early diagnosis of an infection based on antibody detection might lead to less invasive, early interventions. Our study examined antibody-based assays against the biofilm-upregulated antigens SAOCOL0486 (a lipoprotein), glucosaminidase (a domain of SACOL1062), and SACOL0688 (the manganese transporter MntC) for detection of chronic infection. We evaluated these antigens by enzyme-linked immunosorbent assay (ELISA) using sera from naive rabbits and rabbits with -mediated osteomyelitis, and then we validated a proof of concept for the lateral flow assay (LFA). The SACOL0688 LFA demonstrated 100% specificity and 100% sensitivity. We demonstrated the clinical diagnostic utility of the SACOL0688 antigen using synovial fluid (SF) from humans with orthopedic implant infections. Elevated antibody levels to SACOL0688 in clinical SF specimens correlated with 91% sensitivity and 100% specificity for the diagnosis of infection by ELISA. We found measuring antibodies levels to SACOL0688 in SF using ELISA or LFA provides a tool for the sensitive and specific diagnosis of prosthetic joint infection. Development of the LFA diagnostic modality is a desirable, cost-effective option, potentially providing rapid readout in minutes for chronic biofilm infections.
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http://dx.doi.org/10.1128/JCM.01414-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180261PMC
April 2020

Clearance of Staphylococcus aureus from Models of Chronic Infection by Immunization Requires Both Planktonic and Biofilm Antigens.

Infect Immun 2019 12 17;88(1). Epub 2019 Dec 17.

Department of Microbial Pathogenesis, School of Dentistry, University of Maryland-Baltimore, Baltimore, Maryland, USA.

is a causative agent of chronic biofilm-associated infections that are recalcitrant to resolution by the immune system or antibiotics. To combat these infections, an antistaphylococcal, biofilm-specific quadrivalent vaccine against an osteomyelitis model in rabbits has previously been developed and shown to be effective at eliminating biofilm-embedded bacterial populations. However, the addition of antibiotics was required to eradicate remaining planktonic populations. In this study, a planktonic upregulated antigen was combined with the quadrivalent vaccine to remove the need for antibiotic therapy. Immunization with this pentavalent vaccine followed by intraperitoneal challenge of BALB/c mice with resulted in 16.7% and 91.7% mortality in pentavalent vaccine and control groups, respectively ( < 0.001). Complete bacterial elimination was found in 66.7% of the pentavalent cohort, while only 8.3% of the control animals cleared the infection ( < 0.05). Further protective efficacy was observed in immunized rabbits following intramedullary challenge with , where 62.5% of the pentavalent cohort completely cleared the infection, versus none of the control animals ( < 0.05). Passive immunization of BALB/c mice with serum IgG against the vaccine antigens prior to intraperitoneal challenge with prevented mortality in 100% of mice and eliminated bacteria in 33.3% of the challenged mice. These results demonstrate that targeting both the planktonic and biofilm stages with the pentavalent vaccine or the IgG elicited by immunization can effectively protect against infection.
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http://dx.doi.org/10.1128/IAI.00586-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921670PMC
December 2019

Topical therapy for refractory rhinosinusitis caused by methicillin-resistant Staphylococcus aureus: First report in a prospective series.

Auris Nasus Larynx 2018 Oct 6;45(5):994-999. Epub 2018 Feb 6.

Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, United States.

Objective: The incidence of refractory chronic rhinosinusitis (CRS) associated with methicillin-resistant Staphylococcus aureus (MRSA) is rising and remains a therapeutic challenge. The goal of this study is to demonstrate the efficacy of a non-invasive topical therapy against MRSA in these patients.

Methods: Seventeen patients with refractory CRS caused by MRSA were treated with a topical therapy protocol. Treatment consisted of weekly endoscopic sinus debridement followed by intra-sinus installation of a hydroxyl-ethylcellulose gel that releases mometasone and a culture-directed antibiotic for a period of 6 weeks, along with daily nasal nebulization of mometasone with the same antibiotic and saline rinses. Clinical outcome was assessed using the Lund-Kennedy (LK) symptom and endoscopic appearance scores. Sinus mucosal tissue was homogenized and cultured, and microbial biofilm burden was assessed based on colony forming units (CFUs) counts.

Results: Rhinotopic therapy resulted in clearance of MRSA in 13 of 16 patients (81.2%). Treated patients also demonstrated significant improvement clinically as measured by the LK scores. In addition, a significant decrease in mucosal CFUs was observed post-therapy.

Conclusion: Our findings demonstrate that topical therapy is an effective method for treating MRSA-associated refractory CRS.
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http://dx.doi.org/10.1016/j.anl.2018.01.009DOI Listing
October 2018

Sub-inhibitory fosmidomycin exposures elicits oxidative stress in Salmonella enterica serovar Typhimurium LT2.

PLoS One 2014 21;9(4):e95271. Epub 2014 Apr 21.

Department of Chemistry, Northern Arizona University, Flagstaff, Arizona, United States of America.

Fosmidomycin is a time-dependent nanomolar inhibitor of methylerythritol phosphate (MEP) synthase, which is the enzyme that catalyzes the first committed step in the MEP pathway to isoprenoids. Importantly, fosmidomycin is one of only a few MEP pathway-specific inhibitors that exhibits antimicrobial activity. Most inhibitors identified to date only exhibit activity against isolated pathway enzymes. The MEP pathway is the sole route to isoprenoids in many bacteria, yet has no human homologs. The development of inhibitors of this pathway holds promise as novel antimicrobial agents. Similarly, analyses of the bacterial response toward MEP pathway inhibitors provides valuable information toward the understanding of how emergent resistance may ultimately develop to this class of antibiotics. We have examined the transcriptional response of Salmonella enterica serovar typhimurium LT2 to sub-inhibitory concentrations of fosmidomycin via cDNA microarray and RT-PCR. Within the regulated genes identified by microarray were a number of genes encoding enzymes associated with the mediation of reactive oxygen species (ROS). Regulation of a panel of genes implicated in the response of cells to oxidative stress (including genes for catalases, superoxide dismutases, and alkylhydrogen peroxide reductases) was investigated and mild upregulation in some members was observed as a function of fosmidomycin exposure over time. The extent of regulation of these genes was similar to that observed for comparable exposures to kanamycin, but differed significantly from tetracycline. Furthermore, S. typhimurium exposed to sub-inhibitory concentrations of fosmidomycin displayed an increased sensitivity to exogenous H2O2 relative to either untreated controls or kanamycin-treated cells. Our results suggest that endogenous oxidative stress is one consequence of exposures to fosmidomycin, likely through the temporal depletion of intracellular isoprenoids themselves, rather than other mechanisms that have been proposed to facilitate ROS accumulation in bacteria (e.g. cell death processes or the ability of the antibiotic to redox cycle).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095271PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994034PMC
January 2015

Mucosal expression of aquaporin 5 and epithelial barrier proteins in chronic rhinosinusitis with and without nasal polyps.

Am J Otolaryngol 2014 May-Jun;35(3):377-83. Epub 2013 Dec 7.

Center for Microbial Genetics and Genomics, Northern Arizona University; Flagstaff.

Objectives: The purpose of this study is to characterize the association between altered epithelial barrier function, represented by changes in histology and differential expression of the mucosal water membrane permeability protein aquaporin 5 (AQP5), and the pathophysiology of chronic refractory sinusitis (CRS) in patients with and without nasal polyposis.

Study Design: Prospective clinical study.

Setting: Tertiary rhinology referral center.

Participants: Sinonasal samples were obtained from seven CRS subjects with nasal polyps (CRSwNP), seven CRS without nasal polyposis (CRSsNP), and five control healthy patients.

Methods: Mucosal membrane changes were evaluated through hematoxylin and eosin staining of the membrane barrier and immunohistochemical staining of AQP5 expression, a membrane channel protein that affects trans-epithelial water permeability and tissue edema. AQP5 expression was confirmed by real-time PCR (rt-PCR) and western blot. Levels of other membrane proteins, including E-cadherin and Septin-2, were also assessed.

Results: CRSwNP patients showed substantial histologic evidence of membrane remodeling with increased edema and glandular hyperplasia. The epithelial expression of AQP5 was significantly lower in CRSwNP as compared to CRSsNP or control. There was no significant difference in the expression of E-cadherin and Septin-2.

Conclusions: Collectively, these data suggest that the mucosal epithelial barrier is compromised in the context of CRS (predominantly in CRSwNP) when compared to control and that AQP5 acts as a key tight junction protein in the maintenance of mucosal water homeostasis. We hypothesize that AQP5 plays a possible role in the pathophysiology of mucosal edema and polyp formation.
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http://dx.doi.org/10.1016/j.amjoto.2013.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906045PMC
December 2014

Expression of antimicrobial drug tolerance by attached communities of Mycobacterium tuberculosis.

Pathog Dis 2014 Apr 24;70(3):359-69. Epub 2014 Feb 24.

Department of Microbiology, Immunology and Pathology, Mycobacterial Research Laboratories, Colorado State University, Fort Collins, CO, USA.

There is an urgent need to improve methods used to screen antituberculosis drugs. An in vitro assay was developed to test drug treatment strategies that specifically target drug-tolerant Mycobacterium tuberculosis. The H37Rv strain of M. tuberculosis survived antimicrobial treatment as attached microbial communities when maintained in tissue culture media (RPMI-1640) with or without lysed human peripheral blood leukocytes. When cultured planktonically in the presence of Tween-80, bacilli failed to form microbial communities or reach logarithmic phase growth yet remained highly susceptible to antimicrobial drugs. In the absence of Tween, bacilli tolerated drug therapy by forming complex microbial communities attached to untreated well surfaces or to the extracellular matrix derived from lysed human leukocytes. Treatment of microbial communities with DNase I or Tween effectively dispersed bacilli and restored drug susceptibility. These data demonstrate that in vitro expression of drug tolerance by M. tuberculosis is linked to the establishment of attached microbial communities and that dispersion of bacilli targeting the extracellular matrix including DNA restores drug susceptibility. Modifications of this in vitro assay may prove beneficial in a high-throughput platform to screen new antituberculosis drugs especially those that target drug-tolerant bacilli.
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http://dx.doi.org/10.1111/2049-632X.12144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361083PMC
April 2014

Mycobacterium tuberculosis pellicles express unique proteins recognized by the host humoral response.

Pathog Dis 2014 Apr 26;70(3):347-58. Epub 2014 Feb 26.

Graduate Program in Molecular Microbiology and Immunology, University of Maryland, Baltimore, Baltimore, MD, USA.

Mycobacterium tuberculosis (MTB) causes both acute and chronic infections in humans characterized by tolerance to antibiotics and reactivation to cause secondary tuberculosis. These characteristics have led to renewed interest in the in vitro pellicle, or biofilm mode of growth, where bacteria grow to produce a thick aggregate at the air-liquid interface and exhibit increased phenotypic resistance to antibiotics. We infected guinea pigs with the virulent H37Rv strain of MTB for 60 days at which point we collected blood. To identify antigenic proteins, membrane protein extracts of MTB H37Ra pellicles and shaken cultures grown for 3, 5, or 7 weeks were probed with the infected animals' sera after the proteins were separated by two-dimensional gel electrophoresis (2DGE). Antigenic proteins were then identified using MALDI-TOF/TOF mass spectrometry peptide mass fingerprinting. Antigenic pellicle proteins were compared across the three timepoints to identify those that were produced consistently during pellicle growth. They were also compared to those membrane proteins identified from harvested shaken cultures to determine pellicle-specific vs. universally expressed proteins. Using this technique, we identified 44 distinct antigenic proteins, nine of which were pellicle-specific. The sequence of antigenic pellicle-specific proteins was checked for sequence conservation across 15 sequenced MTB clinical isolates, three other members of the MTB complex, as well as M. avium and M. smegmatis. The antigenic pellicle-specific protein Rv0097 was found to have very high sequence conservation within the MTB complex but not with related mycobacteria, while FabG4 was highly conserved in all mycobacteria analyzed. These conserved pellicle-specific proteins represent targets for the development of future diagnostic tests and vaccines.
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http://dx.doi.org/10.1111/2049-632X.12142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363115PMC
April 2014

Topical gel therapy for sinonasal polyposis in Samter's triad: preliminary report.

Ann Otol Rhinol Laryngol 2012 Nov;121(11):719-24

Division of Rhinology, Dept of Otolaryngology-Head and Neck Surgery, Union Memorial Hospital, 201 E University Pkwy, Baltimore, MD 21218, USA.

Objectives: Rhinosinusitis and polyposis are difficult to treat in patients with Samter's triad; they commonly recur despite sinus surgery, antibiotics, and/or nasal steroids. The present study assesses the efficacy of a multimodal regimen that includes topical corticosteroids and antibiotics delivered through a hydroxyethyl cellulose gel and by nebulization.

Methods: Eleven patients with Samter's triad who had polyposis and rhinosinusitis that recurred despite endoscopic sinus surgery were treated with a 6-week course of multimodal topical therapy consisting of a hydroxyethyl cellulose gel that releases corticosteroids and antibiotics, topical nebulization of corticosteroids and antibiotics, saline solution rinses, and sinus debridement. Clinical outcomes were evaluated by Lund-Kennedy endoscopic and symptom scores. Histologic assessment was evaluated by hematoxylin and eosin staining before and after treatment.

Results: Both Lund-Kennedy symptom and endoscopic scores showed.a progressive and statistically significant decline throughout the course of treatment, reaching at 6 weeks 42% of the pretreatment values (p = 0.005) for the Lund-Kennedy symptom score and 34% (p = 0.002) for the endoscopic score, respectively; however, the significance of the improvement was lost with time.

Conclusions: Topical gel therapy improves clinical symptoms, endoscopic findings, and sinus membrane histologic features in patients with refractory Samter's triad, but the improvement is transient, suggesting that a longer therapeutic period might be needed.
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http://dx.doi.org/10.1177/000348941212101104DOI Listing
November 2012

Regulation of murine sinonasal cilia function by microbial secreted factors.

Int Forum Allergy Rhinol 2012 Mar-Apr;2(2):104-10. Epub 2012 Jan 17.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA.

Background: Chronic rhinosinusitis is a multifactorial disease resulting in impaired mucociliary clearance. Recent literature suggests that different bacterial species are associated with varied disease severity. We examined the immediate effect of microbial secreted factors on sinonasal ciliary function.

Methods: Murine primary sinonasal cultures were established in an air-liquid interface (ALI). Bacterial supernatants were isolated from H. influenza, S. pneumoniae, S. aureus, and P. aeruginosa cultures, as well as co-cultures of H. influenza/S. pneumoniae and S. aureus/P. aeruginosa. Controlling for pH and osmolarity, supernatants were administered at 50% concentration to the apical surface of the ALI culture. Basal ciliary beat frequency (CBF) was recorded for 20 minutes, at 5-minute intervals. Control groups were treated with culture broth. At minimum, experiments were performed in triplicate. Stimulated CBF was recorded after mechanical stimulation via short bursts of pressurized air (55 mmHg).

Results: All supernatants reduced basal CBF. S. pneumoniae and P. aeruginosa caused significant reduction in CBF at all time points, with the largest decrease of -46.3 ± 1.6% (p < 0.001) for S. pneumoniae and -27.1 ± 2.8% (p < 0.001) for P. aeruginosa. S. aureus caused the basal CBF to decline by -33.0 ± 2.8% (p < 0.001) at 5 minutes, which reversed by 20 minutes. Overall, H. influenza yielded the least change in CBF (-20.0 ± 2.8%, p < 0.002). Co-cultures (H. influenza/S. pneumoniae and S. aureus/P. aeruginosa) resulted in delayed CBF reduction compared with monocultures. P. aeruginosa also blunted stimulated CBF (p < 0.02).

Conclusion: Results demonstrated acute decreases in murine sinonasal CBF after exposure to bacterial supernatants. Moreover, P. aeruginosa resulted in diminished ciliary stimulation capacity.
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http://dx.doi.org/10.1002/alr.21002DOI Listing
August 2012

Regulation of virulence gene expression resulting from Streptococcus pneumoniae and nontypeable Haemophilus influenzae interactions in chronic disease.

PLoS One 2011 5;6(12):e28523. Epub 2011 Dec 5.

Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona, United States of America.

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal cavity mediated, in part, by polymicrobial communities of bacteria. Recent molecular studies have confirmed the importance of Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) in CRS. Here, we hypothesize that interaction between S. pneumoniae and NTHi mixed-species communities cause a change in bacterial virulence gene expression. We examined CRS as a model human disease to validate these polymicrobial interactions. Clinical strains of S. pneumoniae and NTHi were grown in mono- and co-culture in a standard biofilm assay. Reverse transcriptase real-time PCR (RTqPCR) was used to measure gene expression of key virulence factors. To validate these results, we investigated the presence of the bacterial RNA transcripts in excised human tissue from patients with CRS. Consequences of physical or chemical interactions between microbes were also investigated. Transcription of NTHi type IV pili was only expressed in co-culture in vitro, and expression could be detected ex vivo in diseased tissue. S. pneumoniae pyruvate oxidase was up-regulated in co-culture, while pneumolysin and pneumococcal adherence factor A were down-regulated. These results were confirmed in excised human CRS tissue. Gene expression was differentially regulated by physical contact and secreted factors. Overall, these data suggest that interactions between H. influenzae and S. pneumoniae involve physical and chemical mechanisms that influence virulence gene expression of mixed-species biofilm communities present in chronically diseased human tissue. These results extend previous studies of population-level virulence and provide novel insight into the importance of S. pneumoniae and NTHi in CRS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028523PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230614PMC
July 2012

Population differences in host immune factors may influence survival of Gunnison's prairie dogs (Cynomys gunnisoni) during plague outbreaks.

J Wildl Dis 2011 Oct;47(4):968-73

Center for Microbial Genetics and Genomics, Northern Arizona University, PO Box 4073, Flagstaff, Arizona 86011, USA.

Over the past 40 yr, epizootics of plague (Yersinia pestis) in northern Arizona have reduced populations of the Gunnison's prairie dog (Cynomys gunnisoni), with the exception of a large population found in the Aubrey Valley (AV). To examine potential mechanisms accounting for their survival, we collected prairie dog serum samples in 2005-2006 from AV and a neighboring population near Seligman (SE), Arizona. We quantified gene expression at 58 diverse immune proteins using a multiplexed enzyme-linked immunosorbent assay panel. We found a subset of proteins important in coagulation and inflammation (tissue factor [TF], calbindin [Cal], and thrombopoietin [TPO]) and T-cell responses (CD40L and CD40) that were present in AV at levels two to eight times greater than SE. These results suggest that AV and SE animals might differ in their ability to mount an immune response.
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http://dx.doi.org/10.7589/0090-3558-47.4.968DOI Listing
October 2011

In vitro antimicrobial studies of silver carbene complexes: activity of free and nanoparticle carbene formulations against clinical isolates of pathogenic bacteria.

J Antimicrob Chemother 2012 Jan 3;67(1):138-48. Epub 2011 Oct 3.

Department of Biological Sciences, Northern Arizona University, PO Box 5640, Building 21, Flagstaff, AZ 86011, USA.

Objectives: Silver carbenes may represent novel, broad-spectrum antimicrobial agents that have low toxicity while providing varying chemistry for targeted applications. Here, the bactericidal activity of four silver carbene complexes (SCCs) with different formulations, including nanoparticles (NPs) and micelles, was tested against a panel of clinical strains of bacteria and fungi that are the causative agents of many skin and soft tissue, respiratory, wound, blood, and nosocomial infections.

Methods: MIC, MBC and multidose experiments were conducted against a broad range of bacteria and fungi. Time-release and cytotoxicity studies of the compounds were also carried out. Free SCCs and SCC NPs were tested against a panel of medically important pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter baumannii (MRAB), Pseudomonas aeruginosa, Burkholderia cepacia and Klebsiella pneumoniae.

Results: All four SCCs demonstrated strong efficacy in concentration ranges of 0.5-90 mg/L. Clinical bacterial isolates with high inherent resistance to purified compounds were more effectively treated either with an NP formulation of these compounds or by repeated dosing. Overall, the compounds were active against highly resistant bacterial strains, such as MRSA and MRAB, and were active against the biodefence pathogens Bacillus anthracis and Yersinia pestis. All of the medically important bacterial strains tested play a role in many different infectious diseases.

Conclusions: The four SCCs described here, including their development as NP therapies, show great promise for treating a wide variety of bacterial and fungal pathogens that are not easily killed by routine antimicrobial agents.
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http://dx.doi.org/10.1093/jac/dkr408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236053PMC
January 2012

Suppression of the inflammatory immune response prevents the development of chronic biofilm infection due to methicillin-resistant Staphylococcus aureus.

Infect Immun 2011 Dec 26;79(12):5010-8. Epub 2011 Sep 26.

Department of Microbial Pathogenesis, Dental School, University of Maryland-Baltimore, Baltimore, MD 21201, USA.

Staphylococcus aureus is a common cause of prosthetic implant infections, which can become chronic due to the ability of S. aureus to grow as a biofilm. Little is known about adaptive immune responses to these infections in vivo. We hypothesized that S. aureus elicits inflammatory Th1/Th17 responses, associated with biofilm formation, instead of protective Th2/Treg responses. We used an adapted mouse model of biofilm-mediated prosthetic implant infection to determine chronic infection rates, Treg cell frequencies, and local cytokine levels in Th1-biased C57BL/6 and Th2-biased BALB/c mice. All C57BL/6 mice developed chronic S. aureus implant infection at all time points tested. However, over 75% of BALB/c mice spontaneously cleared the infection without adjunctive therapy and demonstrated higher levels of Th2 cytokines and anti-inflammatory Treg cells. When chronic infection rates in mice deficient in the Th2 cytokine interleukin-4 (IL-4) via STAT6 mutation in a BALB/c background were assessed, the mice were unable to clear the S. aureus implant infection. Additionally, BALB/c mice depleted of Treg cells via an anti-CD25 monoclonal antibody (MAb) were also unable to clear the infection. In contrast, the C57BL/6 mice that were susceptible to infection were able to eliminate S. aureus biofilm populations on infected intramedullary pins once the Th1 and Th17 responses were diminished by MAb treatment with anti-IL-12 p40. Together, these results indicate that Th2/Treg responses are mechanisms of protection against chronic S. aureus implant infection, as opposed to Th1/Th17 responses, which may play a role in the development of chronic infection.
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http://dx.doi.org/10.1128/IAI.05571-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232664PMC
December 2011

Staphylococcus aureus biofilms: properties, regulation, and roles in human disease.

Virulence 2011 Sep-Oct;2(5):445-59. Epub 2011 Sep 1.

Department of Microbial Pathogenesis, Dental School, University of Maryland, Baltimore, MD, USA.

Increasing attention has been focused on understanding bacterial biofilms and this growth modality's relation to human disease. In this review we explore the genetic regulation and molecular components involved in biofilm formation and maturation in the context of the Gram-positive cocci, Staphylococcus aureus. In addition, we discuss diseases and host immune responses, along with current therapies associated with S. aureus biofilm infections and prevention strategies.
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http://dx.doi.org/10.4161/viru.2.5.17724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322633PMC
February 2012

Murine immune response to a chronic Staphylococcus aureus biofilm infection.

Infect Immun 2011 Apr 31;79(4):1789-96. Epub 2011 Jan 31.

epartment of Microbial Pathogenesis, Dental School, University of Maryland, Baltimore, Maryland, USA.

Staphylococcus aureus has reemerged as an important human pathogen in recent decades. Although many infections caused by this microbial species persist through a biofilm mode of growth, little is known about how the host's adaptive immune system responds to these biofilm infections. In this study, S. aureus cells adhered to pins in culture and were subsequently inserted into the tibiae of C57BL/6 mice, with an infecting dose of 2 × 10⁵ CFU. This model was utilized to determine local cytokine levels, antibody (Ab) function, and T cell populations at multiple time points throughout infection. Like human hosts, S. aureus implant infection was chronic and remained localized in 100% of C57BL/6 mice at a consistent level of approximately 10(7) CFU/gram bone tissue after day 7. This infection persisted locally for >49 days and was recalcitrant to clearance by the host immune response and antimicrobial therapy. Local inflammatory cytokines of the Th1 (interleukin-2 [IL-2], IL-12 p70, tumor necrosis factor alpha [TNF-α], and IL-1β) and Th17 (IL-6 and IL-17) responses were upregulated throughout the infection, except IL-12 p70, which dwindled late in the infection. In addition, Th1 Ab subtypes against a biofilm antigen (SA0486) were upregulated early in the infection, while Th2 Abs and anti-inflammatory regulatory T cells (Tregs) were not upregulated until later. These results indicate that early Th1 and Th17 inflammatory responses and downregulated Th2 and Treg responses occur during the development of a chronic biofilm implant infection. This unrestrained inflammatory response may cause tissue damage, thereby enabling S. aureus to attach and thrive in a biofilm mode of growth.
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http://dx.doi.org/10.1128/IAI.01386-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067568PMC
April 2011

Resolution of Staphylococcus aureus biofilm infection using vaccination and antibiotic treatment.

Infect Immun 2011 Apr 10;79(4):1797-803. Epub 2011 Jan 10.

Department of Microbial Pathogenesis, University of Maryland-Baltimore, Baltimore, MD 21201, USA.

Staphylococcus aureus infections, particularly those from methicillin-resistant strains (i.e., MRSA), are reaching epidemic proportions, with no effective vaccine available. The vast number and transient expression of virulence factors in the infectious course of this pathogen have made the discovery of protective antigens particularly difficult. In addition, the divergent planktonic and biofilm modes of growth with their accompanying proteomic changes also demonstrate significant hindrances to vaccine development. In this study, a multicomponent vaccine was evaluated for its ability to clear a staphylococcal biofilm infection. Antigens (glucosaminidase, an ABC transporter lipoprotein, a conserved hypothetical protein, and a conserved lipoprotein) were chosen since they were found in previous studies to have upregulated and sustained expression in a biofilm, both in vitro and in vivo. Antibodies against these antigens were first used in microscopy studies to localize their expression in in vitro biofilms. Each of the four antigens showed heterogeneous production in various locations within the complex biofilm community in the biofilm. Based upon these studies, the four antigens were delivered simultaneously as a quadrivalent vaccine in order to compensate for this varied production. In addition, antibiotic treatment was also administered to clear the remaining nonattached planktonic cells since the vaccine antigens may have been biofilm specific. The results demonstrated that when vaccination was coupled with vancomycin treatment in a biofilm model of chronic osteomyelitis in rabbits, clinical and radiographic signs of infection significantly reduced by 67 and 82%, respectively, compared to infected animals that were either treated with vancomycin or left untreated. In contrast, vaccination alone resulted in a modest, and nonsignificant, decrease in clinical (34% reduction) and radiographic signs (9% reduction) of infection, compared to nonvaccinated animal groups untreated or treated with vancomycin. Lastly, MRSA biofilm infections were significantly cleared in 87.5% of vaccinated and antibiotic-treated animals, while antibiotics or vaccine alone could not significantly clear infection compared to controls (55.6, 22.2, and 33.3% clearance rates, respectively). This approach to vaccine development may lead to the generation of vaccines against other pathogenic biofilm bacteria.
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http://dx.doi.org/10.1128/IAI.00451-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067561PMC
April 2011

Microbial interactions and differential protein expression in Staphylococcus aureus -Candida albicans dual-species biofilms.

FEMS Immunol Med Microbiol 2010 Aug 7;59(3):493-503. Epub 2010 Jun 7.

Graduate Program in Life Sciences, Molecular Microbiology and Immunology Program, University of Maryland - Baltimore, Baltimore, MD, USA.

The fungal species Candida albicans and the bacterial species Staphylococcus aureus are responsible for a majority of hospital-acquired infections and often coinfect critically ill patients as complicating polymicrobial biofilms. To investigate biofilm structure during polymicrobial growth, dual-species biofilms were imaged with confocal scanning laser microscopy. Analyses revealed a unique biofilm architecture where S. aureus commonly associated with the hyphal elements of C. albicans. This physical interaction may provide staphylococci with an invasion strategy because candidal hyphae can penetrate through epithelial layers. To further understand the molecular mechanisms possibly responsible for previously demonstrated amplified virulence during coinfection, protein expression studies were undertaken. Differential in-gel electrophoresis identified a total of 27 proteins to be significantly differentially produced by these organisms during coculture biofilm growth. Among the upregulated staphylococcal proteins was l-lactate dehydrogenase 1, which confers resistance to host-derived oxidative stressors. Among the downregulated proteins was the global transcriptional repressor of virulence factors, CodY. These findings demonstrate that the hyphae-mediated enhanced pathogenesis of S. aureus may not only be due to physical interactions but can also be attributed to the differential regulation of specific virulence factors induced during polymicrobial growth. Further characterization of the intricate interaction between these pathogens at the molecular level is warranted, as it may aid in the design of novel therapeutic strategies aimed at combating fungal-bacterial polymicrobial infection.
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http://dx.doi.org/10.1111/j.1574-695X.2010.00710.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936118PMC
August 2010

Synthesis and in vitro Efficacy Studies of Silver Carbene Complexes on Biosafety Level 3 Bacteria.

Eur J Inorg Chem 2009 May;2009(13):1739-1745

Department of Chemistry, University of Akron, Akron, OH 44325-3601, USA.

A series of N-heterocyclic carbene silver complexes have been synthesized and tested against the select group of bio-safety level 3 bacteria Burkholderia pseudomallei, Burkholderia mallei, Bacillus anthracis, methicillin-resistant Staphylococcus aureus and Yersinia pestis. Minimal inhibitory concentrations, minimal bactericidal and killing assays demonstrated the exceptional efficacy of the complexes against these potentially weaponizable pathogens.
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http://dx.doi.org/10.1002/ejic.200801159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755586PMC
May 2009

Flagellum-mediated biofilm defense mechanisms of Pseudomonas aeruginosa against host-derived lactoferrin.

Infect Immun 2009 Oct 3;77(10):4559-66. Epub 2009 Aug 3.

Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona 86001, USA.

Chronic infection with the gram-negative organism Pseudomonas aeruginosa is a leading cause of morbidity and mortality in human patients, despite high doses of antibiotics used to treat the various diseases this organism causes. These infections are chronic because P. aeruginosa readily forms biofilms, which are inherently resistant to antibiotics as well as the host's immune system. Our laboratory has been investigating specific mutations in P. aeruginosa that regulate biofilm bacterial susceptibility to the host. To continue our investigation of the role of genetics in bacterial biofilm host resistance, we examined P. aeruginosa biofilms that lack the flgK gene. This mutant lacks flagella, which results in defects in early biofilm development (up to 36 h). For these experiments, the flgK-disrupted strain and the parental strain (PA14) were used in a modified version of the 96-well plate microtiter assay. Biofilms were challenged with freshly isolated human leukocytes for 4 to 6 h and viable bacteria enumerated by CFU. Subsequent to the challenge, both mononuclear cells (monocytes and lymphocytes) and neutrophils, along with tumor necrosis factor alpha (TNF-alpha), were required for optimal killing of the flgK biofilm bacteria. We identified a cytokine cross talk network between mononuclear cells and neutrophils that was essential to the production of lactoferrin and bacterial killing. Our data suggest that TNF-alpha is secreted from mononuclear cells, causing neutrophil activation, resulting in the secretion of bactericidal concentrations of lactoferrin. These results extend previous studies of the importance of lactoferrin in the innate immune defense against bacterial biofilms.
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http://dx.doi.org/10.1128/IAI.00075-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747969PMC
October 2009

Biofilms in chronic rhinosinusitis: a review.

Am J Rhinol Allergy 2009 May-Jun;23(3):255-60

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.

Background: Bacterial biofilms consist of a complex, organized community of bacteria that anchor to both biotic and abiotic surfaces. They are composed of layers of embedded, live bacteria within extruded exopolymeric matrix. This configuration allows for evasion of host defenses and decreased susceptibility to antibiotic therapy while maintaining the ability to deliberately release planktonic bacteria, resulting in recurrent acute infections. Thus, bacterial biofilms were hypothesized to contribute to the progression and persistence of chronic rhinosinusitis.

Methods: This review summarizes several of the seminal papers supporting this hypothesis.

Results: Multiple reports using various imaging modalities have demonstrated the presence of biofilms in sinonasal mucosa of patients with chronic rhinosinusitis. More recently, several studies have correlated the presence of biofilms with poor clinical outcomes in the disease process. Early therapeutic interventions have generated mixed results.

Conclusions: Bacterial biofilms appear to contribute to the progression of chronic rhinosinusitis in a subset of patients, although substantial effort toward therapeutic intervention is still necessary.
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http://dx.doi.org/10.2500/ajra.2009.23.3319DOI Listing
July 2009

The relationship of biofilms to chronic rhinosinusitis.

Curr Opin Otolaryngol Head Neck Surg 2008 Jun;16(3):237-41

Otolaryngology-Head and Neck Surgery, Naval Medical Center, San Diego, California, USA.

Purpose Of Review: To provide an update on the state of biofilm research in otolaryngology.

Recent Findings: Chronic rhinosinusitis is a polymicrobial infection, which includes planktonic and biofilm infections with bacterial and fungal elements. The importance of genetic shift in microbes, when converting into a biofilm state, as well as the multiple phenotypes in each bacterial colony cannot be overemphasized. This creates a very sophisticated community of pathogens, some of which will likely survive a simple chemical treatment. Sinus cultures cannot be expected to provide a complete knowledge of the cause of chronic sinusitis. A new diagnostic method and innovative treatment plans will be necessary to provide a lasting treatment of chronic rhinosinusitis. Surgery combined with postoperative treatment is the most effective mean of controlling the majority of chronic rhinosinusitis infections. The challenges associated with the treatment of chronic rhinosinusitis patients may be met by focusing more on the community of microorganism present in the sinuses.

Summary: The understanding of the implication of chronic biofilm infections is growing rapidly but will require an enormous effort to completely control chronic rhinosinusitis.
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http://dx.doi.org/10.1097/MOO.0b013e3282fdc6d5DOI Listing
June 2008

Biofilms with fungi in chronic rhinosinusitis.

Otolaryngol Head Neck Surg 2008 May;138(5):641-7

Otolaryngology Department, Naval Medical Center San Diego, San Diego, CA 92134-1005, USA.

Objectives: Demonstrate that bacterial biofilm in sinus mucosal samples from patients with eosinophilic mucin chronic rhinosinusitis (EMCRS) and allergic fungal rhinosinusitis (AFRS) contains fungal elements; identify specific organisms in the biofilm.

Methods: Mucosa samples from 11 patients undergoing sinus surgery were collected. Patients were classified as having AFRS, EMCRS, or chronic rhinosinusitis (CRS) based on histopathologic findings. Three mucosal samples from controls were also collected. Samples were stained with specific bacterial fluorescent in situ hybridization (FISH) DNA probes (Haemophilus influenzae, Streptococcus pneumophilia, Staphylococcus aureus, and Pseudomonas aeruginosa) and a general pan-fungal FISH probe. The samples were analyzed for bacterial biofilm ultrastructure and fungal elements using epifluorescent microscopy.

Results: Bacterial biofilm was demonstrated in 9/11 samples and 2/3 controls. H. influenzae was the predominant biofilm present. There was a trend showing more fungal elements in AFRS and EMCRS biofilms than in CRS and controls.

Conclusion: This is a preliminary study demonstrating fungal elements within sinus mucosal biofilm and demonstrating biofilm in AFRS.
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http://dx.doi.org/10.1016/j.otohns.2008.02.002DOI Listing
May 2008

Osteomyelitis and the role of biofilms in chronic infection.

FEMS Immunol Med Microbiol 2008 Jan 11;52(1):13-22. Epub 2007 Dec 11.

Department of Microbiology and Immunology, University of Maryland-Baltimore, School of Medicine, Baltimore, MD 21201, USA.

Understanding the mechanisms implicated in the initial attachment, development, and maturation of a biofilm phenotype are of tremendous importance for their effect on the medical, industrial, and public health arenas. This review explores the current understanding of the nature of biofilms and the impact that molecular interactions between the bacteria themselves, as well as between bacteria and the host, may have on biofilm development and phenotype using the nonmotile Gram-positive coccus, Staphylococcus aureus, as an example.
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http://dx.doi.org/10.1111/j.1574-695X.2007.00357.xDOI Listing
January 2008

Immunoglobulins to surface-associated biofilm immunogens provide a novel means of visualization of methicillin-resistant Staphylococcus aureus biofilms.

Appl Environ Microbiol 2007 Oct 24;73(20):6612-9. Epub 2007 Aug 24.

Department of Biomedical Sciences, Dental School, University of Maryland-Baltimore, 650 W. Baltimore Street, Room 9414, Baltimore, MD 21201, USA.

Antigens from the methicillin-resistant Staphylococcus aureus (MRSA) cell wall have been shown to be immunogenic in vivo and upregulated during biofilm growth. In this study, we created purified, recombinant forms of selected antigens and biofilm-upregulated, cell wall-associated proteins. These proteins were shown to cause a robust polyclonal immunoglobulin G (IgG) response when used to immunize rabbits. Antibodies against these recombinant proteins bound to the native forms of each protein as harvested from in vitro grown biofilms of MRSA, as determined both via Western blot analysis and immunofluorescence confocal microscopy. These IgGs could be utilized as imaging tools that localize to areas of specific protein production within a biofilm. This work illustrates that immunogenic, cell wall-associated, biofilm-upregulated proteins are promising for in vitro visualization of biofilm growth, architecture, and space-function relationships.
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http://dx.doi.org/10.1128/AEM.00855-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2075055PMC
October 2007

Phenotypic and functional characterization of Bacillus anthracis biofilms.

Microbiology (Reading) 2007 Jun;153(Pt 6):1693-1701

Northern Arizona University, Flagstaff, AZ 86001, USA.

Biofilms, communities of micro-organisms attached to a surface, are responsible for many chronic diseases and are often associated with environmental reservoirs or lifestyles. Bacillus anthracis is a Gram-positive, endospore-forming bacterium and is the aetiological agent of pulmonary, gastrointestinal and cutaneous anthrax. Anthrax infections are part of the natural lifecycle of many ruminants in North America, including cattle and bison, and B. anthracis is thought to be a central part of this ecosystem. However, in endemic areas in which humans and livestock interact, chronic cases of cutaneous anthrax are commonly reported. This suggests that biofilms of B. anthracis exist in the environment and are part of the ecology associated with its lifecycle. Currently, there are few data that account for the importance of the biofilm mode of life in B. anthracis, yet biofilms have been characterized in other pathogenic and non-pathogenic Bacillus species, including Bacillus cereus and Bacillus subtilis, respectively. This study investigated the phenotypic and functional role of biofilms in B. anthracis. The results demonstrate that B. anthracis readily forms biofilms which are inherently resistant to commonly prescribed antibiotics, and that antibiotic resistance is not solely the function of sporulation.
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http://dx.doi.org/10.1099/mic.0.2006/003376-0DOI Listing
June 2007

Bacterial biofilms on the sinus mucosa of human subjects with chronic rhinosinusitis.

Laryngoscope 2006 Jul;116(7):1121-6

Department of Otolaryngology, Naval Medical Center San Diego, San Diego, California 92134-2200, USA.

Introduction: Chronic rhinosinusitis (CRS) is a common disease poorly controlled by antibiotics. Postulated etiologies of CRS include allergy, fungi, functional factors, and biofilm.

Objectives: We presented a preliminary study demonstrating bacterial biofilms' presence on the sinus mucosa of patients with CRS using fluorescent in situ hybridization (FISH). The advantage of FISH in biofilm identification is that it is the only method that identifies the specific bacteria creating the biofilm matrix. We now present the results of a larger series of patients.

Methods: Patients with CRS scheduled for sinus surgery were enrolled in the study. Biopsies of the sinus mucosa and cultures were taken at the time of surgery. Control samples were taken from patients undergoing septoplasty. Specimens underwent FISH testing for Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenza, and Pseudomonas aeruginosa.

Results: Bacterial biofilms were present on 14 of 18 specimens. The predominant species were H. influenzae, S. pneumoniae, and S. aureus. P. aeruginosa biofilm was not identified on any specimens. The intraoperative cultures of the planktonic bacteria present in the sinuses did not correlate with the biofilms identified. Two of the five control samples were positive for biofilm.

Conclusion: The presence of biofilms on the mucosa of patients with CRS offers a possible cause of antimicrobial therapy failure and could change the approach to treatment. However, the presence of biofilms on healthy control samples implies that biofilms may simply be colonizers. The precise role that biofilms play in CRS still remains to be determined. Further studies with larger sample sizes are needed.
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http://dx.doi.org/10.1097/01.mlg.0000221954.05467.54DOI Listing
July 2006

Identification of Staphylococcus aureus proteins recognized by the antibody-mediated immune response to a biofilm infection.

Infect Immun 2006 Jun;74(6):3415-26

Department of Biomedical Sciences, Dental School, University of Maryland-Baltimore, 666 W. Baltimore Street, Rm. 4-G-11, Baltimore, MD 21201, USA.

Staphylococcus aureus causes persistent, recurrent infections (e.g., osteomyelitis) by forming biofilms. To survey the antibody-mediated immune response and identify those proteins that are immunogenic in an S. aureus biofilm infection, the tibias of rabbits were infected with methicillin-resistant S. aureus to produce chronic osteomyelitis. Sera were collected prior to infection and at 14, 28, and 42 days postinfection. The sera were used to perform Western blot assays on total protein from biofilm grown in vitro and separated by two-dimensional gel electrophoresis. Those proteins recognized by host antibodies in the harvested sera were identified via matrix-assisted laser desorption ionization-time of flight analysis. Using protein from mechanically disrupted total and fractionated biofilm protein samples, we identified 26 and 22 immunogens, respectively. These included a cell surface-associated beta-lactamase, lipoprotein, lipase, autolysin, and an ABC transporter lipoprotein. Studies were also performed using microarray analyses and confirmed the biofilm-specific up-regulation of most of these genes. Therefore, although the biofilm antigens are recognized by the immune system, the biofilm infection can persist. However, these proteins, when delivered as vaccines, may be important in directing the immune system toward an early and effective antibody-mediated response to prevent chronic S. aureus infections. Previous works have identified S. aureus proteins that are immunogenic during acute infections, such as sepsis. However, this is the first work to identify these immunogens during chronic S. aureus biofilm infections and to simultaneously show the global relationship between the antigens expressed during an in vivo infection and the corresponding in vitro transcriptomic and proteomic gene expression levels.
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http://dx.doi.org/10.1128/IAI.00392-06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1479260PMC
June 2006

The exopolysaccharide alginate protects Pseudomonas aeruginosa biofilm bacteria from IFN-gamma-mediated macrophage killing.

J Immunol 2005 Dec;175(11):7512-8

Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, USA.

The ability of Pseudomonas aeruginosa to form biofilms and cause chronic infections in the lungs of cystic fibrosis patients is well documented. Numerous studies have revealed that P. aeruginosa biofilms are highly refractory to antibiotics. However, dramatically fewer studies have addressed P. aeruginosa biofilm resistance to the host's immune system. In planktonic, unattached (nonbiofilm) P. aeruginosa, the exopolysaccharide alginate provides protection against a variety of host factors yet the role of alginate in protection of biofilm bacteria is unclear. To address this issue, we tested wild-type strains PAO1, PA14, the mucoid cystic fibrosis isolate, FRD1 (mucA22+), and the respective isogenic mutants which lacked the ability to produce alginate, for their susceptibility to human leukocytes in the presence and absence of IFN-gamma. Human leukocytes, in the presence of recombinant human IFN-gamma, killed biofilm bacteria lacking alginate after a 4-h challenge at 37 degrees C. Bacterial killing was dependent on the presence of IFN-gamma. Killing of the alginate-negative biofilm bacteria was mediated through mononuclear cell phagocytosis since treatment with cytochalasin B, which prevents actin polymerization, inhibited leukocyte-specific bacterial killing. By direct microscopic observation, phagocytosis of alginate-negative biofilm bacteria was significantly increased in the presence of IFN-gamma vs all other treatments. Addition of exogenous, purified alginate to the alginate-negative biofilms restored resistance to human leukocyte killing. Our results suggest that although alginate may not play a significant role in bacterial attachment, biofilm development, and formation, it may play an important role in protecting mucoid P. aeruginosa biofilm bacteria from the human immune system.
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http://dx.doi.org/10.4049/jimmunol.175.11.7512DOI Listing
December 2005

Endotoxin level measurement in hemodialysis biofilm using "the whole blood assay".

Artif Organs 2005 Jun;29(6):475-81

College of Pharmacy, Paris, France.

Biofilms have been found on the inner surface of silicone tubing inside dialysis machines. Endotoxin releasing from those biofilms increases the bioincompatibility of dialysis liquids and leads to long-term inflammatory complications among dialysis patients. Endotoxin measurement is recommended for the control of dialysis liquids. This article describes the use of a new method, the Whole Blood Assay (WBA), for endotoxin quantification in dialysis biofilms. Biofilms were suspended in sterile water by scraping the tubing samples. Diluted blood samples from healthy donors were stimulated overnight with the contaminated suspension. Stimulated mononuclear cells released IL-1beta in response to endotoxins. IL-1beta level was then measured using an ultrasensitive ELISA method. We demonstrated a semilogarithmic model in which the optical densities measured after the ELISA assay increases linearly with the levels of endotoxin. This model allowed the determination of the amount of endotoxins in biofilm samples with a detection limit of 0.032 EU/mL. Most of the time, the amounts of endotoxin measured by the WBA were higher than those measured by the Limulus Amoebocyte Lysate (LAL) assay. This study suggested the presence of "endotoxin-like" compounds different from the lipopolysaccharides that are not detected by the LAL assay. We concluded that the LAL is necessary but insufficient to have a representative quantification of endotoxins that could be hazardous to patient health.
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http://dx.doi.org/10.1111/j.1525-1594.2005.29081.xDOI Listing
June 2005

Impact of polyunsaturated fatty acids on cytoskeletal linkage of L-selectin.

Cell Immunol 2004 Apr;228(2):91-8

Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, USA.

Polyunsaturated fatty acid [omega-3 polyunsaturated fatty acids (omega-3PUFAs)] incorporation into cell membranes has been shown to have potent anti-inflammatory activity, though the mechanisms involved are only partially characterized. Here, we show that PUFA enrichment of T cell membranes decreased the overall expression of L-selectin as well as a highly conserved epitope on L-selectin that may serve as a marker for optimal protein function. Additionally, PUFA enrichment inhibited L-selectin cytoskeletal association, which is thought to be important for optimal functional activity. In support of this, PUFA enrichment of gammadelta T cell membranes reduced L-selectin-dependent rolling interactions under conditions mimicking physiological flow. Taken together, these data suggest that the anti-inflammatory activity of omega-3 polyunsaturated fatty acids may be due, in part, to a novel effect on L-selectin, namely PUFA reduction or prevention of cytoskeletal association of L-selectin.
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http://dx.doi.org/10.1016/j.cellimm.2004.04.004DOI Listing
April 2004