Think before you prescribe: how dentistry contributes to antibiotic resistance.

Antibiotic resistance presents a daunting challenge to health professionals worldwide and has the potential to create major problems for modern health care, resulting in more medical expenditure, extended hospital stays and increased morbidity and mortality. Advanced genome sequencing technologies present a complex picture of resistance, extending our understanding beyond the pharmacotherapeutic interface between pathogens and antibiotics. This review discusses the global scope and scale of antibiotic resistance and contextualizes it for the dental practitioner, emphasizing the role we must play in limiting the progression of resistance through antibiotic stewardship and disease prevention.

Metagenomic Insights into Transferable Antibiotic Resistance in Oral Bacteria.

Antibiotic resistance is considered one of the greatest threats to global public health. Resistance is often conferred by the presence of antibiotic resistance genes (ARGs), which are readily found in the oral microbiome. In-depth genetic analyses of the oral microbiome through metagenomic techniques reveal a broad distribution of ARGs (including novel ARGs) in individuals not recently exposed to antibiotics, including humans in isolated indigenous populations. This has resulted in a paradigm shift from focusing on the carriage of antibiotic resistance in pathogenic bacteria to a broader concept of an oral resistome, which includes all resistance genes in the microbiome. Metagenomics is beginning to demonstrate the role of the oral resistome and horizontal gene transfer within and between commensals in the absence of selective pressure, such as an antibiotic. At the chairside, metagenomic data reinforce our need to adhere to current antibiotic guidelines to minimize the spread of resistance, as such data reveal the extent of ARGs without exposure to antimicrobials and the ecologic changes created in the oral microbiome by even a single dose of antibiotics. The aim of this review is to discuss the role of metagenomics in the investigation of the oral resistome, including the transmission of antibiotic resistance in the oral microbiome. Future perspectives, including clinical implications of the findings from metagenomic investigations of oral ARGs, are also considered.

Epigenetics: a new frontier in dentistry.

In 2007, only four years after the completion of the Human Genome Project, the journal Science announced that epigenetics was the 'breakthrough of the year'. Time magazine placed it second in the top 10 discoveries of 2009. While our genetic code (i.e. our DNA) contains all of the information to produce the elements we require to function, our epigenetic code determines when and where genes in the genetic code are expressed. Without the epigenetic code, the genetic code is like an orchestra without a conductor. Although there is now a substantial amount of published research on epigenetics in medicine and biology, epigenetics in dental research is in its infancy. However, epigenetics promises to become increasingly relevant to dentistry because of the role it plays in gene expression during development and subsequently potentially influencing oral disease susceptibility. This paper provides a review of the field of epigenetics aimed specifically at oral health professionals. It defines epigenetics, addresses the underlying concepts and provides details about specific epigenetic molecular mechanisms. Further, we discuss some of the key areas where epigenetics is implicated, and review the literature on epigenetics research in dentistry, including its relevance to clinical disciplines. This review considers some implications of epigenetics for the future of dental practice, including a 'personalized medicine' approach to the management of common oral diseases.

Sexual dimorphism in deciduous crown traits of a European derived Australian sample.

Sex determination of juvenile skeletal remains is a problematic area affecting physical anthropology, forensic science and archaeology. Sexual dimorphism in the morphometric crown traits of the deciduous dentition may be used to help resolve this issue. Dental stone casts from a European derived Australian sample (n=151) were used to investigate variation within crown traits of the deciduous canine and molars. The metric traits investigated were crown size, trigonid size and talonid size. The morphological features included Carabelli's trait and molar cusp number. Metric crown traits were significantly larger in males (p<0.05). The morphological crown traits were not significantly different between the sexes. The largest degree of sexual dimorphism was 11.11% in the trigonid mesiodistal diameter of the first deciduous molar. This is the first recording of the measurement in a European derived sample. Two multivariate statistics, linear functional discriminant analysis and binary logistic regression, were used to determine the success rate of sex classification from the crown traits. The most suitable was linear functional discriminant analysis, however similar results were found when using binary logistic regression. When using all variables investigated in this study, sex could be classified with accuracy of 70.2% from linear functional discriminant analysis (cross validated). The mandibular teeth had greater sexual dimorphism, classifying sex correctly 74.8% of the time compared to maxillary variables that had a success rate of 55.6%. Our results have shown that morphometric crown traits in the deciduous dentition can be used to classify sex of juvenile skeletons (11 months to 12 years) of European descent from linear functional discriminant analysis with accuracy between 70.2% and 74.8%.

Factors associated with reading-plus-spelling retardation and specific spelling retardation.

Factors associated with reading-plus-spelling retardation and specific spelling retardation were investigated in a large sample of Dunedin children who were studied longitudinally between the ages of three and 11 years. Those with reading-plus-spelling retardation showed poor performance on WISC-R Verbal subtests relative to non-retarded children, but superior performance on Picture Completion and Object Assembly subtests. The group with reading-plus-spelling retardation also had poor speech articulation but no significant language, motor or neurological dysfunction. Their educational attainment in reading, writing and mathematics was consistently poor. Specific spelling retardation was associated with deficits on WISC-R Arithmetic and Coding subtests, teacher ratings of low attentiveness and poor achievement in writing and mathematics. No language, motor or neurological deficits were apparent in this group.

The genome-linked protein of picornaviruses. VIII. Complete amino acid sequence of poliovirus VPg and carboxy-terminal analysis of its precursor, P3-9.

VPg, the genome-linked protein of poliovirus, and its putative precursor P3-9, were radiolabelled and subjected to carboxypeptidase-A digestion. The release of amino acids was followed by identification and quantification on an amino acid analyser. Both proteins were found to be co-terminal with a sequence of -valyl-glutamine-COOH, an observation that provides further evidence that host cell trimming of virus-specific peptides does not play a role in poliovirus protein processing. Radiolabelled VPg was subjected to automated Edman degradation. The combined results complete the structural analysis of VPg, a polypeptide 22 amino acids in length with a molecular weight of 2354. Only one form of VPg has been found linked to virion RNA and it originates by a cleavage at glutaminyl-glycine pairs at both termini. The observation is consistent with other cleavages found in the virus processing scheme.

Primary structure, gene organization and polypeptide expression of poliovirus RNA.

The primary structure of the poliovirus genome has been determined. The RNA molecule is 7,433 nucleotides long, polyadenylated at the 3' terminus, and covalently linked to a small protein (VPg) at the 5' terminus. An open reading frame of 2,207 consecutive triplets spans over 89% of the nucleotide sequence and codes for the viral polyprotein NCVPOO. Twelve viral polypeptides have been mapped by amino acid sequence analysis and were found to be proteolytic cleavage products of the polyprotein, cleavages occurring predominantly at Gln-Gly pairs.

The genome-linked protein of picornaviruses. VII. Genetic mapping of poliovirus VPg by protein and RNA sequence studies.

The poliovirus genome-linked protein (VPg) has been subjected to radiochemical microsequence analysis. Sequence studies of virion RNA by a modification of Sanger's dideoxy method have revealed a base sequence corresponding to the amino acid analysis. This result proves that VPg is virus-encoded. The RNA sequence has allowed us to predict the total amino acid sequence of VPg and part of its precursor. VPg is, at most, 27 amino acids long. It maps within the 3' terminal segment of the viral genome that encodes the precursor polypeptide NCVP1b for the virus-specific RNA polymerase NCVP4.