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  • 1
    In: Infection and Immunity, 2007, Vol. 75(6), p.2929
    Description: Although Moraxella catarrhalis continues to be a significant cause of disease in both children and adults, the steps involved in pathogenesis remain poorly understood. We have identified three open reading frames in the M. catarrhalis genome that encode homologues of the two-partner secretion system (TPS). The sequenced M. catarrhalis hemagglutinin-like locus of strain 7169 has a unique gene organization composed in the order of mchA1, mchB, and mchA2, where mchA1 is divergent. MchA1 and MchA2 are 74% identical at the amino acid level and diverge only in the C-terminal regions. The TPS motif identified in the common N-terminal regions of MchA1 and MchA2 was found to be homologous to the filamentous hemagglutinin of Bordetella pertussis, and MchB has homology to other TpsB transporters. The presence of MchA1 and MchA2 in outer membrane protein preparations and concentrated culture supernatants (CCSs) of strain 7169 was confirmed by immunoblotting using specific antisera. Nanoscale liquid chromatography-tandem mass spectrometry peptide sequencing of the antibody-reactive bands from the CCSs was performed and demonstrated that 13 different peptides mapped to identical regions of MchA1 and MchA2. Quantitative adherence assays revealed a decrease of binding to primary normal human bronchial epithelial cells by the mch mutants 7169mchB and 7169mchA1A2B compared to that by the wild-type strain. These studies show that MchA1, MchA2, and MchB are components of a novel TPS identified in M. catarrhalis and suggest that these proteins may be involved in colonization.
    Keywords: Medicine ; Biology;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 2
    Language: English
    In: Gene, 2011, Vol.477(1), pp.19-23
    Description: is a Gram-negative aerobic diplococcus that is a mucosal pathogen of the upper and lower respiratory tracts in humans. In order to colonize the human host and establish an infection, must be able to effectively attach to the respiratory mucosal epithelia. Although little is known about pathogenesis, our laboratory has previously shown that expression of type IV pili (TFP) contributes to mucosal colonization. TFP are filamentous surface appendages primarily composed of a single protein subunit termed pilin, which is encoded by in . These surface structures play a crucial role in the initiation of disease by a wide range of pathogenic bacteria. Our studies also indicate that unlike the pilin of the pathogenic species, which exhibit both phase and antigenic variation, the pilin subunit of appears to be more highly conserved as there are no major pilin variants produced by a single strain and only two major PilA antigenic variants, termed clade 1 and clade 2, have been observed between strains. Moreover, we have determined that these highly conserved bacterial surface structures are expressed by all clinical isolates evaluated. Therapeutic or vaccine-based interventions that prevent or diminish nasopharyngeal colonization will likely decrease acute and recurrent infections in prone populations. Thus, our data indicate that additional studies aimed at elucidating the role of PilA in the pathogenesis and host response to infections are warranted.
    Keywords: Pili ; Pilin ; Antigenic Clades ; Engineering ; Biology ; Anatomy & Physiology
    ISSN: 0378-1119
    E-ISSN: 1879-0038
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  • 3
    Language: English
    In: Biomaterials, February 2015, Vol.41, pp.97-105
    Description: Effective treatment options are often limited for implant-associated orthopedic infections. In this study we evaluated the antimicrobial effects of applying cathodic voltage-controlled electrical stimulation (CVCES) of -1.8 V (vs. Ag/AgCl) to commercially pure titanium (cpTi) substrates with preformed biofilm-like structures of methicillin-resistant Staphylococcus aureus (MRSA). The in vitro studies showed that as compared to the open circuit potential (OCP) conditions, CVCES of -1.8 V for 1 h significantly reduced the colony-forming units (CFU) of MRSA enumerated from the cpTi by 97% (1.89 × 106 vs 6.45 × 104 CFU/ml) and from the surrounding solution by 92% (6.63 × 105 vs. 5.15 × 104 CFU/ml). The in vivo studies, utilizing a rodent periprosthetic infection model, showed that as compared to the OCP conditions, CVCES at -1.8 V for 1 h significantly reduced MRSA CFUs in the bone tissue by 87% (1.15 × 105 vs. 1.48 × 104 CFU/ml) and reduced CFU on the cpTi implant by 98% (5.48 × 104 vs 1.16 × 103 CFU/ml). The stimulation was not associated with histological changes in the host tissue surrounding the implant. As compared to the OCP conditions, the −1.8 V stimulation significantly increased the interfacial capacitance (18.93 vs. 98.25 μF/cm ) and decreased polarization resistance (868,250 vs. 108 Ω-cm ) of the cpTi. The antimicrobial effects are thought to be associated with these voltage-dependent electrochemical surface properties of the cpTi.
    Keywords: Titanium ; Infection ; Electrical Stimulation ; Antimicrobial ; Bacteria ; Biofilm ; Medicine ; Engineering
    ISSN: 0142-9612
    E-ISSN: 1878-5905
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  • 4
    In: Lasers in Surgery and Medicine, November 2014, Vol.46(9), pp.712-717
    Keywords: Antimicrobial Photodynamic Therapy ; Biofilm ; Gram‐Negative Bacteria ; Otitis Media ; Photofrin
    ISSN: 0196-8092
    E-ISSN: 1096-9101
    Source: John Wiley & Sons, Inc.
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  • 5
    Language: English
    In: Lasers in surgery and medicine, November 2014, Vol.46(9), pp.712-7
    Description: Moraxella catarrhalis is a significant cause of pediatric otitis media (OM), which is the most prevalent bacterial infection in children and primary reason for antibiotic administration in this population. Moreover, biofilm formation has been implicated as a primary mechanism of chronic or recurrent OM disease. As bacterial biofilms are inherently resistant to most antibiotics and these complex structures also present a significant challenge to the immune system, there is a clear need to identify novel antimicrobial approaches to treat OM infections. In this study, we evaluated the potential efficacy of antibacterial photodynamic therapy (aPDT) with porfimer sodium (Photofrin (PF)) against planktonic as well as biofilm-associated M. catarrhalis. The bactericidal activity of aPDT with PF was assessed against multiple recent clinical isolates of M. catarrhalis grown planktonically as well as in biofilms. The bactericidal activity of PF-aPDT was quantified by enumeration of colony forming units post-treatment. The effect of aPDT on M. catarrhalis biofilms was further investigated with scanning electron microscopy (SEM) imaging. aPDT with PF significantly reduced M. catarrhalis viability. Although PF-aPDT caused higher killing in planktonic grown organisms (5-6 log kill), biofilm grown bacteria also demonstrated a statistically significant reduction in viable organisms (3-4 log decrease in recoverable bacteria) following treatment as compared to saline only controls (P 〈 0.01). SEM studies indicated the PF-aPDT treated bacteria exhibited prominent morphological changes with visibly distorted cell membranes. aPDT with PF elicits significant bactericidal activity against both planktonic and biofilm-associated M. catarrhalis, suggesting this technology warrants further analysis as a potential novel antimicrobial treatment for acute or recurrent OM.
    Keywords: Antimicrobial Photodynamic Therapy ; Biofilm ; Gram-Negative Bacteria ; Otitis Media ; Photofrin ; Photochemotherapy ; Biofilms -- Drug Effects ; Dihematoporphyrin Ether -- Pharmacology ; Moraxella (Branhamella) Catarrhalis -- Drug Effects ; Photosensitizing Agents -- Pharmacology
    ISSN: 01968092
    E-ISSN: 1096-9101
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  • 6
    Language: English
    In: mSphere, 01 May 2019, Vol.4(3), p.e00178-19
    Description: Periprosthetic joint infections (PJIs) develop clinically in the presence of antibiotic therapies and are responsible for increased patient morbidity and rising health care costs. Many of these infections involve bacterial biofilm formation on orthopedic hardware, and it has been well established that these biofilms are refractory to most antibiotic treatments. Recent studies have focused on novel methods to prevent and eradicate infection. Cathodic-voltage-controlled electrical stimulation (CVCES) has previously been shown to be effective as a method for prevention and eradication of Gram-positive and Gram-negative infections. The present study revealed that the utility of CVCES for prevention and eradication of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is enhanced in the presence of clinically relevant antibiotics. The synergistic effects of CVCES and antibiotics are effective in a magnitude-dependent manner. The results of this study indicate a promising alternative method to current PJI mitigation techniques.Periprosthetic joint infection (PJI) develops clinically, even with antibiotic treatment, and methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can perpetuate resistance, further complicating the use of noninvasive treatments. This study evaluated cathodic-voltage-controlled electrical stimulation (CVCES) of titanium, in combination with a clinically relevant antibiotic, to synergistically prevent MRSA and P. aeruginosa PJIs by inhibiting bacterial adherence or as a treatment for eradicating established biofilms. CVCES of −1.0 V, −1.5 V, or −1.8 V (versus Ag/AgCl), with or without vancomycin for MRSA or gentamicin for P. aeruginosa, was applied to sterile titanium incubated with cultures to evaluate prevention of attachment or eradication of preestablished biofilms. Treatments were 24 h long and included open-circuit potential controls, antibiotic alone, CVCES, and CVCES plus antibiotic. Biofilm-associated and planktonic CFU were enumerated. In general, CVCES at −1.8 V alone or with antibiotic completely eradicated biofilm-associated CFU for both strains, and these parameters were also highly effective against planktonic bacteria, resulting in a 〉6-log reduction in MRSA and no detectable planktonic P. aeruginosa. All CFU were reduced ∼3 to 5 logs from controls for prevention CVCES plus antibiotics at −1.0 V and −1.5 V against MRSA. Remarkably, there were no detectable P. aeruginosa CFU following prevention CVCES at −1.0 V or −1.5 V with gentamicin. Our results suggest that CVCES in combination with antibiotics may be an effective approach for prevention and treatment of PJI.
    Keywords: Orthopedic Infection ; Treatment ; Prevention ; Bacteria ; Biofilms ; Biology
    E-ISSN: 2379-5042
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  • 7
    In: PLoS ONE, 2016, Vol.11(7)
    Description: This work aimed to develop an in vivo approach for measuring the duration of human bioaerosol infectivity. To achieve this, techniques designed to target short-term and long-term bioaerosol aging, were combined in a tandem system and optimized for the collection of human respiratory bioaerosols, without contamination. To demonstrate the technique, cough aerosols were sampled from two persons with cystic fibrosis and chronic Pseudomonas aeruginosa infection. Measurements and cultures from aerosol ages of 10, 20, 40, 900 and 2700 seconds were used to determine the optimum droplet nucleus size for pathogen transport and the airborne bacterial biological decay. The droplet nuclei containing the greatest number of colony forming bacteria per unit volume of airborne sputum were between 1.5 and 2.6 μm. Larger nuclei of 3.9 μm, were more likely to produce a colony when impacted onto growth media, because the greater volume of sputum comprising the larger droplet nuclei, compensated for lower concentrations of bacteria within the sputum of larger nuclei. Although more likely to produce a colony, the larger droplet nuclei were small in number, and the greatest numbers of colonies were instead produced by nuclei from 1.5 to 5.7 μm. Very few colonies were produced by smaller droplet nuclei, despite their very large numbers. The concentration of viable bacteria within the dried sputum comprising the droplet nuclei exhibited an orderly dual decay over time with two distinct half-lives. Nuclei exhibiting a rapid biological decay process with a 10 second half-life were quickly exhausted, leaving only a subset characterized by a half-life of greater than 10 minutes. This finding implied that a subset of bacteria present in the aerosol was resistant to rapid biological decay and remained viable in room air long enough to represent an airborne infection risk.
    Keywords: Research Article ; Physical Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Physical Sciences ; Physical Sciences ; Medicine And Health Sciences ; Physical Sciences ; Physical Sciences
    E-ISSN: 1932-6203
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  • 8
    Language: English
    In: Microbes and Infection, March 2011, Vol.13(3), pp.261-275
    Description: is a category A select agent based on its infectivity and virulence but disease mechanisms in infection remain poorly understood. Murine pulmonary models of infection were therefore employed to assess and compare dissemination and pathology and to elucidate the host immune response to infection with the highly virulent Type A . strain Schu4 versus the less virulent Type B live vaccine strain (LVS). We found that dissemination and pathology in the spleen was significantly greater in mice infected with . Schu4 compared to mice infected with . LVS. Using gene expression profiling to compare the response to infection with the two .  strains, we found that there were significant differences in the expression of genes involved in the apoptosis pathway, antigen processing and presentation pathways, and inflammatory response pathways in mice infected with Schu4 when compared to LVS. These transcriptional differences coincided with marked differences in dissemination and severity of organ lesions in mice infected with the Schu4 and LVS strains. Therefore, these findings indicate that altered apoptosis, antigen presentation and production of inflammatory mediators explain the differences in pathogenicity of . Schu4 and LVS.
    Keywords: Francisella Tularensis ; Immune ; Bacterial ; Microarray ; Pathology ; Biology
    ISSN: 1286-4579
    E-ISSN: 1769-714X
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  • 9
    Language: English
    In: Nature (London), 01 November 2017, Vol.551
    Description: Our growing awareness of the importance and diversity of the microbial world contrasts starkly with our limited understanding of its fundamental structure. Despite remarkable advances in DNA sequence generation, a lack of standardized protocols and common analytical framework impede useful comparison between studies, hindering development of global inferences about microbial life on Earth. Here, we show that with coordinated protocols, exact microbial 16S rRNA gene sequences can be followed across scores of individual studies, revealing patterns of diversity, community structure, and life history strategy at a planetary scale. Using 27,751 crowdsourced environmental samples comprising more than 2.2 billion reads, we find sharp divides between host-associated and free-living communities. We show that the distribution of taxonomic and sequence diversity follows consistent trends across samples types and along gradients of environmental parameters, highlighting some of the global evolutionary patterns and ecological principles that underpin Earth’s microbiome. Here, this dataset provides the most complete environmental survey of our microbial world to date, and serves as a growing reference to provide immediate global context to future microbial surveys.
    Keywords: Environmental Sciences ; Microbiome ; Earth ; Global ; Basic Biological Sciences ; Sciences (General) ; Environmental Sciences ; Physics
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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