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Biomedical subjects

Maxwell H Anderson

Publications and source records attributed to Maxwell H Anderson.

14 recordsLinked to original sources

Enhancement of antimicrobial activity against pseudomonas aeruginosa by coadministration of G10KHc and tobramycin.

Pseudomonas aeruginosa is a common opportunistic human pathogen that is associated with life-threatening acute infections and chronic airway colonization during cystic fibrosis. Previously, we converted the wide-spectrum antimicrobial peptide novispirin G10 into a selectively-targeted antimicrobial peptide (STAMP), G10KHc. Compared to novispirin G10, the STAMP had an enhanced ability to kill Pseudomonas mendocina. In this study, we explored the activity of G10KHc against P. aeruginosa. G10KHc was found to be highly active (as active as tobramycin) against P. aeruginosa clinical isolates. Most interestingly, we observed a synergistic-like enhancement in killing activity when biofilms and planktonic cultures of P. aeruginosa were cotreated with G10KHc and tobramycin. The data indicate that the mechanism of enhanced activity may involve increased tobramycin uptake due to G10KHc-mediated cell membrane disruption. These results suggest that G10KHc may be useful against P. aeruginosa during acute and chronic infection states, especially when it is coadministered with tobramycin.

Anti-Bacterial Agents↗

Comparative analysis of a monoclonal antibody-based Streptococcus mutans detection method with selective culture assays using polymerase chain reaction as a gold standard.

The aim of this study was to compare a recently developed monoclonal antibody (MAb)-based salivary Streptococcus mutans detection method with various selective media using polymerase chain reaction (PCR) as the gold standard. Salivary S. mutans cells were enumerated with a MAb-based method, along with three commonly used selective media, mitis-salivarius-bacitracin agar (MSB), trypticase yeast-extract cystine sucrose bacitracin agar (TYCSB), and glucose-sucrose-potassium tellurite-bacitracin (GSTB) agar. Statistical analysis showed no significant correlations between each method. With PCR as the standard, a MAb-based detection method was found to provide the highest sensitivity (91%) and specificity (96%) among these four methods. This study demonstrates that the MAb-based detection method may provide more accurate enumeration of salivary S. mutans than selective media.

Animals↗

Targeted killing of Streptococcus mutans by a pheromone-guided "smart" antimicrobial peptide.

Within the repertoire of antibiotics available to a prescribing clinician, the majority affect a broad range of microorganisms, including the normal flora. The ecological disruption resulting from antibiotic treatment frequently results in secondary infections or other negative clinical consequences. To address this problem, our laboratory has recently developed a new class of pathogen-selective molecules, called specifically (or selectively) targeted antimicrobial peptides (STAMPs), based on the fusion of a species-specific targeting peptide domain with a wide-spectrum antimicrobial peptide domain. In the current study, we focused on achieving targeted killing of Streptococcus mutans, a cavity-causing bacterium that resides in a multispecies microbial community (dental plaque). In particular, we explored the possibility of utilizing a pheromone produced by S. mutans, namely, the competence stimulating peptide (CSP), as a STAMP targeting domain to mediate S. mutans-specific delivery of an antimicrobial peptide domain. We discovered that STAMPs constructed with peptides derived from CSP were potent against S. mutans grown in liquid or biofilm states but did not affect other oral streptococci tested. Further studies showed that an 8-amino-acid region within the CSP sequence is sufficient for targeted delivery of the antimicrobial peptide domain to S. mutans. The STAMPs presented here are capable of eliminating S. mutans from multispecies biofilms without affecting closely related noncariogenic oral streptococci, indicating the potential of these molecules to be developed into "probiotic" antibiotics which could selectively eliminate pathogens while preserving the protective benefits of a healthy normal flora.

Anti-Bacterial Agents↗

Adding selectivity to antimicrobial peptides: rational design of a multidomain peptide against Pseudomonas spp.

Currently available antimicrobials exhibit broad killing with regard to bacterial genera and species. Indiscriminate killing of microbes by these conventional antibiotics can disrupt the ecological balance of the indigenous microbial flora, often resulting in negative clinical consequences. Species-specific antimicrobials capable of precisely targeting pathogenic bacteria without damaging benign microorganisms provide a means of avoiding this problem. In this communication, we report the successful creation of the first synthetic, target-specific antimicrobial peptide, G10KHc, via addition of a rationally designed Pseudomonas-specific targeting moiety (KH) to a generally killing peptide (novispirin G10). The resulting chimeric peptide showed enhanced bactericidal activity and faster killing kinetics against Pseudomonas spp. than G10 alone. The enhanced killing activities are due to increased binding and penetration of the outer membrane of Pseudomonas sp. cells. These properties were not observed in tests of untargeted bacterial species, and this specificity allowed G10KHc to selectively eliminate Pseudomonas spp. from mixed cultures. This work lays a foundation for generating target-specific "smart" antimicrobials to complement currently available conventional antibiotics.

Amino Acid Sequence↗

In situ and non-invasive detection of specific bacterial species in oral biofilms using fluorescently labeled monoclonal antibodies.

Noninvasive in situ detection of suspected cariogenic bacterial species within dental biofilms could facilitate monitoring of the dynamic change of oral microbial flora and assist in the assessment of the treatment efficacy of therapeutic agents. In this study, we explore the possibility to use three well-characterized monoclonal antibodies (MAbs) against Streptococcus mutans, Actinomyces naeslundii, and Lactobacillus casei to identify these three important members of the oral microbial community in the complex environment of oral biofilms. These MAbs, which were conjugated to different fluorescent labels and visualized with confocal laser scanning microscopy (CLSM), proved to be an useful tool to identify the three species of interest (S. mutans, A. naeslundii, and L. casei) under various experimental conditions including in vitro and in vivo derived oral biofilms. Manifold addition of the MAbs on consecutive days did not alter the biofilm structure thus allowing monitoring of the same biofilm over extended time periods. Using this MAb-based method the effect of sucrose challenge on the biofilm composition and the distribution of S. mutans, A. naeslundii, and L. casei were examined. S. mutans was found to be the predominant species under the various biofilm conditions tested. These studies indicate that MAbs based bacterial detection with CLSM is a versatile tool which permits new insights into the ecology of oral biofilm development.

Actinomyces↗

Reimbursement for dental implants: dispelling some popular myths.

BACKGROUND AND OVERVIEW: Dental implants are being placed with increasing regularity. Many dentists do not take advantage of insurance coverages for this treatment because they are under the impression that no aspect of implant therapy is covered. This article discusses a number of insurance benefits that may be available to dental patients but not readily apparent to treating dentists and their staff members. CONCLUSIONS AND PRACTICE IMPLICATIONS: Some dentists and patients may assume incorrectly that a dental insurance plan does not reimburse for any implant therapy when, in fact, there may be some benefit available for at least a portion of the treatment. In addition, some dentists and patients may not consider implant therapy even when it is the preferred treatment option because of the assumed lack of reimbursement. Knowing that some reimbursement is available may make the difference in the patient's accepting the best treatment for his or her condition. Furthermore, since an increasing number of patients now make some contribution toward their dental insurance plan premiums, they deserve to know their options and to receive appropriate benefits.

Current Procedural Terminology↗

Future trends in dental benefits.

Dentistry and dental payment systems as we know them today will continue to evolve. Dentistry as practiced today and the prepayment systems of dentistry are substantially different than they were fifty years ago when dental insurance as we know it was first developed. Dentistry has always changed with the development of our science and the expression of dentistry's diseases in the populations we serve. The changes that are likely to occur in the future will be focused on improving health outcomes across risk-analyzed populations with the goals of providing optimal health outcomes at reasonable costs. Dentists will increasingly become engaged in the whole health of their patients. Where sufficient correlations can be leveraged between dentistry and overall health, medical plans will play an increasing role in dentistry's future for two reasons. Given favorably altered therapeutic outcomes for medical systems that preserve scarce resources, it will be an economic imperative to engage the dental system. It will also be the right thing to do from a total health perspective. In the final analysis, this elevates the role of dentistry and empowers the dentist to participate in the total health of their patients.

Delivery of Health Care, Integrated↗

Mutation of luxS affects biofilm formation in Streptococcus mutans.

Quorum sensing is a bacterial mechanism for regulating gene expression in response to changes in population density. Many bacteria are capable of acyl-homoserine lactone-based or peptide-based intraspecies quorum sensing and luxS-dependent interspecies quorum sensing. While there is good evidence about the involvement of intraspecies quorum sensing in bacterial biofilm, little is known about the role of luxS in biofilm formation. In this study, we report for the first time that luxS-dependent quorum sensing is involved in biofilm formation of Streptococcus mutans. S. mutans is a major cariogenic bacterium in the multispecies bacterial biofilm commonly known as dental plaque. An ortholog of luxS for S. mutans was identified using the data available in the S. mutans genome project (http://www.genome.ou.edu/smutans.html). Using an assay developed for the detection of the LuxS-associated quorum sensing signal autoinducer 2 (AI-2), it was demonstrated that this ortholog was able to complement the luxS negative phenotype of Escherichia coli DH5alpha. It was also shown that AI-2 is indeed produced by S. mutans. AI-2 production is maximal during mid- to late-log growth in batch culture. Mutant strains devoid of the luxS gene were constructed and found to be defective in producing the AI-2 signal. There are also marked phenotypic differences between the wild type and the luxS mutants. Microscopic analysis of in vitro-grown biofilm structure revealed that the luxS mutant biofilms adopted a much more granular appearance, rather than the relatively smooth, confluent layer normally seen in the wild type. These results suggest that LuxS-dependent signal may play an important role in biofilm formation of S. mutans.

Amino Acid Sequence↗

A review of the efficacy of chlorhexidine on dental caries and the caries infection.

Chlorhexidine has been used for the past 35 years in the treatment of the two primary diseases of dentistry with varying degrees of success. The purpose of this paper is to review the literature for both the caries reduction potential and the microbiologic reduction of the pathogens associated with dental caries. The literature remains mixed on the success of chlorhexidine for the reduction of dental caries. Its performance as an antimicrobial against Streptococcus mutans is more consistent and favorable.

Anti-Infective Agents, Local↗

Analyses of Streptococcus mutans in saliva with species-specific monoclonal antibodies.

Three species-specific monoclonal antibodies (MAbs) against Streptococcus mutans were used to detect and quantify S. mutans levels in saliva. This study shows that MAb-based salivary S. mutans tests exhibit significantly higher specificity and sensitivity than the commonly used selective culture method. Examination of nearly 2,000 human saliva samples shows that S. mutans counts in human saliva vary from less than 10,000 to a high 36 million cells/mL. Over 15% of the saliva samples examined have salivary S. mutans counts over 500,000 cells/mL. When saliva samples were collected at different time points during a day, the number of salivary S. mutans in the same human subject varied, especially before and after sugar uptake. Additionally, data obtained from stimulated versus unstimulated saliva in the same human subjects differed greatly and appear to be completely uncorrelated. This study provides useful information and tools for analyzing the role of S. mutans in human dental caries.

Antibodies, Bacterial↗

Patterns of oral care in dental school and general dental practice.

This study compared patterns of oral care provided by predoctoral dental students for patients seeking treatment at the University of Washington (UW) with patterns reported for general dental offices by the Washington Dental Service (WDS). Dental care included about 5 million services provided to 880,317 patients by 2,803 WDS general dentists and about 45,600 dental services provided to 9,488 patients by 155 UW dental students during 1999. There was high fidelity between databases and randomly surveyed patient records for treatment provided in both UW (95 percent) and WDS (97 percent) populations. While patient age patterns were generally similar, UW students completed more procedures for young children and for adults older than seventy-four years but completed fewer procedures for age groups of from thirteen to eighteen and from forty-five to fifty-four than general dental offices. The relative mix of all services completed by UW and WDS providers was similar (ANOVA, P=0.82). Within categories of service, the percentage of total services completed by students compared to those submitted by community dentists to WDS was about the same for examinations, radiographs, fluoride and sealants, amalgams, composites, single crowns, and endodontics. The percentage of total procedures completed showed a greater emphasis by UW students on inlays/onlays, dentures, extractions, and periodontal maintenance, and lesser experience with implants, orthodontics, sedation, and emergency procedures than general dental offices. We conclude that the relative distribution of clinical services provided by UW dental students is comparable to those procedures reported to WDS by dental offices in the adjacent community.

Adolescent↗