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  • 1
    In: Infection and Immunity, 2010, Vol. 78(5), p.2017
    Description: Although Acinetobacter baumannii has emerged as a significant cause of nosocomial infections worldwide, there have been few investigations describing the factors important for A. baumannii persistence and pathogenesis. This paper describes the first reported identification of a glycosyltransferase, LpsB, involved in lipopolysaccharide (LPS) biosynthesis in A. baumannii. Mutational, structural, and complementation analyses indicated that LpsB is a core oligosaccharide glycosyl transferase. Using a genetic approach, lpsB was compared with the lpsB homologues of several A. baumannii strains. These analyses indicated that LpsB is highly conserved among A. baumannii isolates. Furthermore, we developed a monoclonal antibody, monoclonal antibody 13C11, which reacts to an LPS core epitope expressed by approximately one-third of the A. baumannii clinical isolates evaluated to date. Previous studies describing the heterogeneity of A. baumannii LPS were limited primarily to structural analyses; therefore, studies evaluating the correlation between these surface glycolipids and pathogenesis were warranted. Our data from an evaluation of LpsB mutant 307::TN17, which expresses a deeply truncated LPS glycoform consisting of only two 3-deoxy-d-manno-octulosonic acid residues and lipid A, suggest that A. baumannii LPS is important for resistance to normal human serum and confers a competitive advantage for survival in vivo. These results have important implications for the role of LPS in A. baumannii infections.
    Keywords: Acinetobacter Baumannii -- Enzymology ; Bacterial Proteins -- Metabolism ; Glycosyltransferases -- Metabolism ; Lipopolysaccharides -- Biosynthesis;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 2
    In: Infection and Immunity, 2010, Vol. 78(9), p.3993
    Description: Acinetobacter baumannii is a pathogen of increasing medical importance with a propensity to be multidrug resistant, thereby making treatment challenging. Little is known of virulence traits in A. baumannii. To identify virulence factors and potential drug targets, random transposon (Tn) mutants derived from the A. baumannii strain AB307-0294 were screened to identify genes essential for growth in human ascites fluid in vitro, an inflammatory exudative fluid. These studies led to the identification of two genes that were predicted to be required for capsule polymerization and assembly. The first, ptk, encodes a putative protein tyrosine kinase (PTK), and the second, epsA, encodes a putative polysaccharide export outer membrane protein (EpsA). Monoclonal antibodies used in flow cytometric and Western analyses confirmed that these genes are required for a capsule-positive phenotype. A capsule-positive phenotype significantly optimized growth in human ascites fluid, survival in human serum, and survival in a rat soft tissue infection model. Importantly, the clearance of the capsule-minus mutants AB307.30 (ptk mutant, capsule minus) and AB307.45 (epsA mutant, capsule minus) was complete and durable. These data demonstrated that the K1 capsule from AB307-0294 was an important protectin. Further, these data suggested that conserved proteins, which contribute to the capsule-positive phenotype, are potential antivirulence drug targets. Therefore, the results from this study have important biologic and translational implications and, to the best of our knowledge, are the first to address the role of capsule in the pathogenesis of A. baumannii infection.
    Keywords: Translation ; Outer Membrane Proteins ; Data Processing ; Polymerization ; Virulence Factors ; Monoclonal Antibodies ; Animal Models ; Survival ; Medical Importance ; Pathogens ; Infection ; Inflammation ; Flow Cytometry ; Transposons ; Ascites ; Protein-Tyrosine Kinase ; Multidrug Resistance ; Soft Tissues ; Capsular Polysaccharides ; Drugs ; Acinetobacter Baumannii ; Microorganisms & Parasites ; Immunology;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 3
    In: Infection and Immunity, 2007, Vol. 75(12), p.5559
    Description: Moraxella catarrhalis is a gram-negative mucosal pathogen of the human respiratory tract. Although little information is available regarding the initial steps of M. catarrhalis pathogenesis, this organism must be able to colonize the human mucosal surface in order to initiate an infection. Type IV pili (TFP), filamentous surface appendages primarily comprised of a single protein subunit termed pilin, play a crucial role in the initiation of disease by a wide range of bacteria. We previously identified the genes that encode the major proteins involved in the biosynthesis of M. catarrhalis TFP and determined that the TFP expressed by this organism are highly conserved and essential for natural transformation. We extended this initial study by investigating the contribution of TFP to the early stages of M. catarrhalis colonization. TFP-deficient M. catarrhalis bacteria exhibit diminished adherence to eukaryotic cells in vitro. Additionally, our studies demonstrate that M. catarrhalis cells form a mature biofilm in continuous-flow chambers and that biofilm formation is enhanced by TFP expression. The potential role of TFP in colonization by M. catarrhalis was further investigated using in vivo studies comparing the abilities of wild-type M. catarrhalis and an isogenic TFP mutant to colonize the nasopharynx of the chinchilla. These results suggest that the expression of TFP contributes to mucosal airway colonization. Furthermore, these data indicate that the chinchilla model of nasopharyngeal colonization provides an effective animal system for studying the early steps of M. catarrhalis pathogenesis.
    Keywords: Transformation ; Colonization ; Data Processing ; Pilin ; Pili ; Mucosa ; Nasopharynx ; Appendages ; Pathogens ; Biofilms ; Infection ; Respiratory Tract ; Moraxella Catarrhalis ; Rodentia ; Cell Biology ; Microorganisms & Parasites;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 4
    Language: English
    In: The Journal of infectious diseases, 15 February 2009, Vol.199(4), pp.513-21
    Description: Acinetobacter baumannii is a bacterial pathogen of increasing medical importance. Little is known about genes important for its survival in vivo. Screening of random transposon mutants of the model pathogen AB307-0294 identified the mutant AB307.27. AB307.27 contained its transposon insertion in pbpG, which encodes the putative low-molecular-mass penicillin-binding protein 7/8 (PBP-7/8). AB307.27 was significantly killed in ascites (P〈.001), but its growth in Luria-Bertani broth was similar to that of its parent, AB307-0294 (P=.13). The survival of AB307.27 was significantly decreased in a rat soft-tissue infection model (P〈.001) and a rat pneumonia model (P=.002), compared with AB307-0294. AB307.27 was significantly killed in 90% human serum in vitro, compared with AB307-0294 (P〈.001). Electron microscopy demonstrated more coccobacillary forms of AB307.27, compared with AB307-0294, suggesting a possible modulation in the peptidoglycan, which may affect susceptibility to host defense factors. These findings demonstrate that PBP-7/8 contributes to the pathogenesis of A. baumannii. PBP-7/8 either directly or indirectly contributes to the resistance of AB307-0294 to complement-mediated bactericidal activity. An understanding of how PBP-7/8 contributes to serum resistance will lend insight into the role of this low-molecular-mass PBP whose function is poorly understood.
    Keywords: Acinetobacter Infections -- Immunology ; Acinetobacter Baumannii -- Growth & Development ; Penicillin-Binding Proteins -- Physiology
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 5
    In: Infection and Immunity, 2008, Vol. 76(8), p.3577
    Description: Acinetobacter baumannii is a bacterial pathogen of increasing medical importance. Little is known about its mechanisms of pathogenesis, and safe reliable agents with predictable activity against A. baumannii are presently nonexistent. The availability of relevant animal infection models will facilitate the study of Acinetobacter biology. In this report we tested the hypothesis that the rat pneumonia and soft-tissue infection models that our laboratory had previously used for studies of extraintestinal pathogenic Escherichia coli were clinically relevant for A. baumannii. Advantages of these models over previously described models were that the animals were not rendered neutropenic and they did not receive porcine mucin with bacterial challenge. Using the A. baumannii model pathogen 307-0294 as the challenge pathogen, the pneumonia model demonstrated all of the features of infection that are critical for a clinically relevant model: namely, bacterial growth/clearance, an ensuing host inflammatory response, acute lung injury, and, following progressive bacterial proliferation, death due to respiratory failure. We were also able to demonstrate growth of 307-0294 in the soft-tissue infection model. Next we tested the hypothesis that the soft-tissue infection model could be used to discriminate between the inherent differences in virulence of various A. baumannii clinical isolates. The ability of A. baumannii to grow and/or be cleared in this model was dependent on the challenge strain. We also hypothesized that complement is an important host factor in protecting against A. baumannii infection in vivo. In support of this hypothesis was the observation that the serum sensitivity of various A. baumannii clinical isolates in vitro roughly paralleled their growth/clearance in the soft-tissue infection model in vivo. Lastly we hypothesized that the soft-tissue infection model would serve as an efficient screening mechanism for identifying gene essentiality for drug discovery. Random mutants of 307-0294 were initially screened for lack of growth in human ascites in vitro. Selected mutants were subsequently used for challenge in the soft-tissue infection model to determine if the disrupted gene was essential for growth in vivo. Using this approach, we have been able to successfully identify a number of genes essential for the growth of 307-0294 in vivo. In summary, these models are clinically relevant and can be used to study the innate virulence of various Acinetobacter clinical isolates and to assess potential virulence factors, vaccine candidates, and drug targets in vivo and can be used for pharmacokinetic and chemotherapeutic investigations.
    Keywords: Medicine ; Biology;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 6
    In: Clinical Orthopaedics and Related Research, 2015, Vol.473(9), pp.2856-2864
    Description: BACKGROUND: Effective treatments for implant-associated infections are often lacking. Cathodic voltage-controlled electrical stimulation has shown potential as a treatment of implant-associated infections of methicillin-resistant Staphylococcus aureus (MRSA). QUESTIONS/PURPOSES: The primary purpose of this study was to (1) determine if cathodic voltage-controlled electrical stimulation combined with vancomycin therapy is more effective at reducing the MRSA bacterial burden on the implant, bone, and synovial fluid in comparison to either treatment alone or no treatment controls. We also sought to (2) evaluate the histologic effects of the various treatments on the surrounding bone; and to (3) determine if the cathodic voltage-controlled electrical stimulation treatment had an effect on the mechanical properties of the titanium implant as a result of possible hydrogen embrittlement. METHODS: Thirty-two adult male Long-Evans rats (Harlan Laboratories, Indianapolis, IN, USA) with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, eight animals received a treatment of cathodic voltage-controlled electrical stimulation at −1.8 V versus Ag/AgCl for 1 hour (STIM), eight received vancomycin twice daily for 1 week (VANCO), eight received the cathodic voltage-controlled electrical stimulation and vancomycin therapy combined (STIM + VANCO), and eight served as controls with no treatment (CONT). Two weeks after initial infection, the implant, bone, and synovial fluid were collected for colony-forming unit (CFU) enumeration, qualitative histological analysis by a pathologist blinded to the treatments each animal received, and implant three-point bend testing. RESULTS: The implant-associated CFU enumerated from the STIM + VANCO (mean, 3.7 × 10; SD, 6.3 × 10) group were less than those from the CONT (mean, 1.3 × 10; SD, 2.8 × 10; 95% confidence interval [CI] of difference, −4.3 × 10 to −9.9 × 10; p 〈 0.001), STIM (mean, 1.4 × 10; SD, 2.0 × 10; 95% CI of difference, −2.1 × 10 to −1.8 × 10; p = 0.002), and VANCO (mean, 5.8 × 10; SD, 5.7 × 10; 95% CI of difference, −6.4 × 10 to −1.7 × 10; p 〈 0.001) group. The bone-associated CFU enumerated from the STIM + VANCO group (6.3 × 10; SD, 1.1 × 10) were less than those from the CONT (mean, 2.8 × 10; SD, 4.8 × 10; 95% CI of difference, −9.4 × 10 to −5.0 × 10; p 〈 0.001) and STIM (mean, 2.6 × 10; SD, 2.5 × 10; 95% CI of difference, −4.1 × 10 to −1.6 × 10; p 〈 0.001) groups. The VANCO group (4.3 × 10; SD, 6.3 × 10) also had lower bone-associated CFU as compared with the CONT (mean 95% CI of difference, −9.3 × 10 to −4.5 × 10; p 〈 0.001) and STIM (95% CI of difference, −4.0 × 10 to −1.5 × 10; p 〈 0.001) groups. In comparison to the synovial fluid CFU enumerated from the CONT group (mean, 3.3 × 10; SD, 6.0 × 10), lower synovial CFU were reported for both the STIM + VANCO group (mean, 4.6 × 10; SD, 1.2 × 10; 95% CI of difference, −4.9 × 10 to −3.0 × 10; p 〈 0.001) and the VANCO group (mean, 6.8 × 10; SD, 9.2 × 10; 95% CI of difference, −4.9 × 10 to −2.8 × 10; p = 0.007). The histological analysis showed no discernable deleterious effects on the surrounding tissue as a result of the treatments. No brittle fracture occurred during mechanical testing and with the numbers available, no differences in implant flexural yield strength were detected between the groups. CONCLUSIONS: In this rodent model, cathodic voltage-controlled electrical stimulation combined with vancomycin is an effective treatment for titanium implant-associated infections showing greater than 99.8% reduction in bacterial burden on the implant, surrounding bone, and synovial fluid as compared with the controls and the stimulation alone groups. CLINICAL RELEVANCE: Cathodic voltage-controlled electrical stimulation combined with vancomycin may enable successful treatment of titanium orthopaedic implant-associated infections with implant retention. Future studies will focus on optimization of the stimulation parameters for complete eradication of infection and the ability to promote beneficial host tissue responses.
    Keywords: Staphylococcus Aureus Infections – Care and Treatment ; Staphylococcus Aureus Infections – Analysis ; Staphylococcus Aureus Infections – Health Aspects ; Vancomycin – Analysis ; Vancomycin – Health Aspects ; Staphylococcus Aureus – Analysis ; Staphylococcus Aureus – Health Aspects ; Microbial Drug Resistance – Care and Treatment ; Microbial Drug Resistance – Analysis ; Microbial Drug Resistance – Health Aspects;
    ISSN: 0009-921X
    E-ISSN: 15281132
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  • 7
    In: Infection and Immunity, 1999, Vol. 67(2), p.681
    Description: Moraxella catarrhalis-induced otitis media continues to be a significant cause of infection in young children, prompting increased efforts at identifying effective vaccine antigens. We have previously demonstrated that M. catarrhalis expresses specific outer membrane proteins (OMPs) in response to iron limitation and that this organism can utilize transferrin and lactoferrin for in vitro growth. One of these proteins, which binds human transferrin, is OMP B1. As the human host presents a naturally iron-limited environment, proteins, like OMP B1, which are expressed in response to this nutritional stress are potential vaccine antigens. In this study, we have developed monoclonal antibody (MAb) 11C6, which reacts to a surface-exposed epitope of OMP B1 expressed by M. catarrhalis 7169. This antibody was used to clone ompB1, and sequence analysis suggested that OMP B1 is the M. catarrhalis homologue to the transferrin binding protein B described for pathogenic Neisseriaceae, Haemophilus influenzae, Actinobacillus pleuropneumoniae, and M. catarrhalis. Expression of recombinant OMP B1 on the surface of Escherichia coli confers transferrin binding activity, confirming that this protein is likely involved in iron acquisition. In addition, ompB1 was used to construct an isogenic mutant in M. catarrhalis 7169. This mutant, termed 7169b12, was used as the control in bactericidal assays designed to determine if OMP B1 elicits protective antibodies. In the presence of MAb 11C6 and human complement, wild-type 7169 demonstrated a 99% decline in viability, whereas the ompB1 isogenic mutant was resistant to this bactericidal activity. Further analysis with MAb 11C6 revealed the presence of this OMP B1 epitope on 31% of the clinical isolates tested. These data suggest that OMP B1 is a potential vaccine antigen against M. catarrhalis infections.
    Keywords: Medicine ; Biology;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 8
    Language: English
    In: Clinical Orthopaedics and Related Research®, 2016, Vol.474(7), pp.1668-1675
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11999-016-4705-7 Byline: Scott R. Nodzo (1), Menachem Tobias (1), Richard Ahn (1), Lisa Hansen (2), Nicole R. Luke-Marshall (2), Craig Howard (1), Linda Wild (3), Anthony A. Campagnari (2), Mark T. Ehrensberger (4) Abstract: Background Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels. Questions/purposes (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? Methods Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/kg, subcutaneous, twice daily for 5 weeks) (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (-1.8 V for 1 hour on postoperative day [POD] 7) (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (-1.8 V for 1 hour on POD 7 and POD 21) or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis of inflammation and granulation tissue present in serial sections of the humeral head for animals in each experimental group. Results The VANCO + 1STIM decreased the implant bacterial burden (median = 0, range = 0--10 CFU/mL) when compared with CONT (median = 5.7 x 10.sup.4, range = 4.0 x 10.sup.3-8.0 x 10.sup.5 CFU/mL difference of medians = -5.6 x 10.sup.4 p 〈 0.001) and VANCO (median = 4.9 x 10.sup.3, range = 9.0 x 10.sup.2-2.1 x 10.sup.4 CFU/mL difference of medians = -4.9 x 10.sup.3 p 〈 0.001). The VANCO + 1STIM decreased the bone bacterial burden (median = 0, range = 0--0 CFU/mL) when compared with CONT (median = 1.3 x 10.sup.2, range = 0--9.4 x 10.sup.2 CFU/mL difference of medians = -1.3 x 10.sup.2 p 〈 0.001) but was not different from VANCO (median = 0, range = 0--1.3 x 10.sup.2 CFU/mL difference of medians = 0 p = 0.210). The VANCO + 2STIM group had implant CFU (median = 0, range = 0--8.0 x 10.sup.1 CFU/mL) and bone CFU (median = 0, range = 0--2.0 x 10.sup.1 CFU/mL) that were not different from the VANCO + 1STIM treatment group implant CFU (median = 0, range = 0--10 CFU/mL difference of medians = 0 p = 0.334) and bone CFU (median = 0, range = 0--0 CFU/mL difference of medians = 0 p = 0.473). The histological analysis showed no deleterious effects on the surrounding tissue as a result of the treatments. Conclusions Using CVCES in combination with prolonged vancomycin resulted in decreased MRSA bacterial burden, and it may be beneficial in treating biofilm-related implant infections. Clinical Relevance CVCES combined with clinically relevant lengths of vancomycin therapy may be a treatment option for IAI and allow for component retention in certain clinical scenarios. However, more animal research and human trials confirming the efficacy of this approach are needed before such a clinical recommendation could be made. Author Affiliation: (1) Department of Orthopedics, State University of New York at Buffalo, Buffalo, NY, USA (2) Department of Microbiology and Immunology, State University of New York at Buffalo, Buffalo, NY, USA (3) Department of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA (4) Department of Biomedical Engineering, State University of New York at Buffalo, 162 Farber Hall, 3435 Main Street, Buffalo, NY, 14214, USA Article History: Registration Date: 08/01/2016 Online Date: 22/01/2016 Article note: The institution of one or more of the authors (MTE) has received, during the study period, funding from the Congressionally Directed Medical Research Program, Peer Reviewed Orthopedic Research Program, and the Bruce Holm Memorial Catalyst Fund. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research [R] editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research [R] neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. A comment to this article is available at http://dx.doi.org/10.1007/s11999-016-4744-0.
    Keywords: Vancomycin – Health Aspects ; Vancomycin – Analysis;
    ISSN: 0009-921X
    E-ISSN: 1528-1132
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  • 9
    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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  • 10
    Language: English
    In: Infection and immunity, March 2013, Vol.81(3), pp.915-22
    Description: The emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (NMR) techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody (MAb) 13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb 13D6. Opsonization of K1-positive strains, but not K1-negative strains, with MAb 13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P 〈 0.05). Lastly, treatment with MAb 13D6 3 and 24 h after bacterial challenge in a rat soft tissue infection model resulted in a significant decrease in the growth/survival of a K1-positive strain compared to that of a K1-negative strain or to treatment with a vehicle control (P 〈 0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment, and pragmatic challenges exist, such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials.
    Keywords: Acinetobacter Infections -- Prevention & Control ; Acinetobacter Baumannii -- Metabolism ; Antibodies, Monoclonal -- Immunology ; Bacterial Capsules -- Metabolism ; Bacterial Vaccines -- Immunology
    ISSN: 00199567
    E-ISSN: 1098-5522
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