Development of an Emergency Department Surge Plan Based on the NEDOCS score.

Context: Emergency Department (ED) overcrowding is a significant problem worldwide. Many factors contribute to ED overcrowding, including staffing shortages, diagnostic testing delays, and inadequate inpatient beds to meet the demand. ED overcrowding results in patient safety issues like higher inpatient mortality and other negative impacts, such as an increased length of stay (LOS) and an increased trend of leaving the ED before undergoing an evaluation and treatment. The National emergency department overcrowding study (NEDOCS) is a scoring system to detect ED overcrowding objectively. Objective: To determine the impact of implementing an ED adult surge plan on ED throughput. Study Design: Prospective single-site study of adults presenting to the ED from January to April 2023. Setting or Dataset: Academic medical center. Population studied: Adult ED patients. Outcome Measures: Mean adult ED hold times, mean ED LOS, left without seen rate, mean door-to-doctor exam time, mean NEDOCS scores. Results: This analysis included 16,701 ED visits and 12,269 patients. During this time, 3,751 (22.5%) patients were admitted to inpatient status, and 1,413 (8.5%) were admitted to observation status. Pre-implementation, the mean ED hold time was 9.9 hours which decreased to 5.7 hours post-implementation (p=0.03). Pre-implementation, the mean ED LOS was 15.4 hours which decreased to 14.1 hours post-implementation (p=ns). Pre-implementation, the left without being seen rate was 4.8%, which decreased to 4.0% post-implementation (p=ns). Pre-implementation, the mean door-to-doctor exam time was 57.6 minutes which decreased to 54.0 minutes postimplementation (p=ns). Pre-implementation, the mean NEDOCS score was 186.2, which decreased to 131.2 post-implementation (p<0.0001). Conclusions: Our study suggests that implementing an ED adult surge plan can significantly improve ED hold hours and NEDOCS scores. However, it is important to note that other important ED throughput metrics (mean ED LOS, left without seen rate, mean door-to-doctor exam time) did not significantly improve. Further research may be necessary to understand the factors contributing to these outcomes and identify additional interventions that may improve ED throughput.

Evasion of early innate immune response by 2'-O-methylation of dengue genomic RNA.

Dengue virus (DENV) is the most prevalent mosquito-borne virus pathogen in humans. There is currently no antiviral therapeutic or widely available vaccine against dengue infection. The DENV RNA genome is methylated on its 5' cap by its NS5 protein. DENV bearing a single E216A point mutation in NS5 loses 2'-O-methylation of its genome. While this mutant DENV is highly attenuated and immunogenic, the mechanism of this attenuation has not been elucidated. In this study, we find that replication of this mutant DENV is attenuated very early during infection. This early attenuation is not dependent on a functional type I interferon response and coincides with early activation of the innate immune response. Taken together, our data suggest that 2'-O-methylation of DENV genomic RNA is important for evasion of the host immune response during the very early stages of infection as the virus seeks to establish infection.

Impact of prescription drug-monitoring program on controlled substance prescribing in the ED.

OBJECTIVE: In 2009, Florida initiated a statewide prescription drug-monitoring program (PDMP) to encourage safer prescribing of controlled substances and reduce drug abuse and diversion. Data supporting the utility of such programs in the emergency department (ED) is scarce. This study sought to determine the effect of PDMP data on controlled substance prescribing from the ED. METHODS: In this pre-post study utilizing a historical control, pharmacists in the ED provided prescribers with a summary of the PDMP data for their patients. The number of controlled substances prescribed in the intervention group was compared with that prescribed in the historical control to determine if the intervention resulted in a change in the average number of controlled substance prescribed. RESULTS: Among the 710 patients evaluated, providing prescribers with PDMP data did not alter the average number of controlled substance per patient prescribed (0.23 controlled substances per patient in the historical control compared with 0.28 controlled substances per patient in the intervention group; 95% confidence interval [CI], -0.016 to 0.116; P = .125). All prescribers surveyed indicated that having PDMP data altered their controlled substance prescribing and felt more comfortable prescribing controlled substances. CONCLUSIONS: Although the results did not demonstrate a change in the average number of controlled substances prescribed when prescribers were provided with PDMP data, results from the survey indicate that prescribers felt the data altered their prescribing of controlled substances, and thus were more contented prescribing controlled substances.

Genomic analysis and growth characteristic of dengue viruses from Makassar, Indonesia.

Dengue fever is currently the most important mosquito-borne viral disease in Indonesia. In South Sulawesi province, most regions report dengue cases including the capital city, Makassar. Currently, no information is available on the serotypes and genotypes of the viruses circulating in the area. To understand the dynamic of dengue disease in Makassar, we carried out dengue fever surveillance study during 2007-2010. A total of 455 patients were recruited, in which antigen and serological detection revealed the confirmed dengue cases in 43.3% of patients. Molecular detection confirmed the dengue cases in 27.7% of patients, demonstrating that dengue places a significant disease burden on the community. Serotyping revealed that dengue virus serotype 1 (DENV-1) was the most predominant serotype, followed by DENV-2, -3, and -4. To determine the molecular evolution of the viruses, we conducted whole-genome sequencing of 80 isolates. Phylogenetic analysis grouped DENV-2, -3 and -4 to the Cosmopolitan genotype, Genotype I and Genotype II, respectively. Intriguingly, each serotype paints a different picture of evolution and transmission. DENV-1 appears to be undergoing a clade replacement with Genotype IV being supplanted by Genotype I. The Cosmopolitan DENV-2 isolates were found to be regionally endemic and is frequently being exchanged between countries in the region. By contrast, DENV-3 and DENV-4 isolates were related to strains with a long history in Indonesia although the DENV-3 strains appear to have been following a distinct evolutionary path since approximately 1998. To assess whether the various DENV serotypes/genotypes possess different growth characteristics, we performed growth kinetic assays on selected viruses. We observed the relatively higher rate of replication for DENV-1 and -2 compared to DENV-3 and -4. Within the DENV-1, viruses from Genotype I grow faster than that of Genotype IV. This higher replication rate may underlie their ability to replace the circulation of Genotype IV in the community.

Exploring the mode of action of bioactive compounds by microfluidic transcriptional profiling in mycobacteria.

Most candidate anti-bacterials are identified on the basis of their whole cell anti-bacterial activity. A critical bottleneck in the early discovery of novel anti-bacterials is tracking the structure activity relationship (SAR) of the novel compounds synthesized during the hit to lead and lead optimization stage. It is often very difficult for medicinal chemists to visualize if the novel compounds synthesized for understanding SAR of a particular scaffold have similar molecular mechanism of action (MoA) as that of the initial hit. The elucidation of the molecular MoA of bioactive inhibitors is critical. Here, a new strategy and routine assay for MoA de-convolution, using a microfluidic platform for transcriptional profiling of bacterial response to inhibitors with whole cell activity has been presented. First a reference transcriptome compendium of Mycobacterial response to various clinical and investigational drugs was built. Using feature reduction, it was demonstrated that subsets of biomarker genes representative of the whole genome are sufficient for MoA classification and deconvolution in a medium-throughput microfluidic format ultimately leading to a cost effective and rapid tool for routine antibacterial drug-discovery programs.

Characterization of early host responses in adults with dengue disease.

BACKGROUND: While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking. METHODS: In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on dengue virus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h) and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. RESULTS: In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut), while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1), CCL8 (MCP-2), CXCL10 (IP-10) and CCL3 (MIP-1α), antimicrobial peptide ß-defensin 1 (DEFB1), desmosome/intermediate junction component plakoglobin (JUP) and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1). CONCLUSIONS: These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease.

A single amino acid in nonstructural protein NS4B confers virulence to dengue virus in AG129 mice through enhancement of viral RNA synthesis.

Dengue (DEN) is a mosquito-borne viral disease that has become an increasing economic and health burden for the tropical and subtropical world. The lack of an appropriate animal model of DEN has greatly impeded the study of its pathogenesis and the development of vaccines/antivirals. We recently reported a DEN virus 2 (DENV-2) strain (D2Y98P) that lethally infects immunocompromised AG129 mice, resulting in organ damage or dysfunction and increased vascular permeability, hallmarks of severe DEN in patients (G. K. Tan et al., PLoS Negl. Trop. Dis. 4:e672, 2010). Here we report the identification of one critical virulence determinant of strain D2Y98P. By mutagenesis, we showed that a Phe-to-Leu alteration at amino acid position 52 in nonstructural protein NS4B completely abolished the pathogenicity of the D2Y98P virus, as evidenced by a lack of lethality and the absence of histological signs of disease, which correlated with reduced viral titers and intact vascular permeability. Conversely, a Leu-to-Phe alteration at position 52 of NS4B in nonvirulent DENV-2 strain TSV01 led to 80% lethality and increased viremia. The NS4B(Phe52) viruses displayed enhanced RNA synthesis in mammalian cells but not in mosquito cells. The increased viral RNA synthesis was independent of the ability of NS4B to interfere with the host type I interferon response. Overall, our results demonstrate that Phe at position 52 in NS4B confers virulence in mice on two independent DENV-2 strains through enhancement of viral RNA synthesis. In addition to providing further insights into the functional role of NS4B protein, our findings further support a direct relationship between viral loads and DEN pathogenesis in vivo, consistent with observations in DEN patients.

The DBCLS BioHackathon: standardization and interoperability for bioinformatics web services and workflows. The DBCLS BioHackathon Consortium*.

Web services have become a key technology for bioinformatics, since life science databases are globally decentralized and the exponential increase in the amount of available data demands for efficient systems without the need to transfer entire databases for every step of an analysis. However, various incompatibilities among database resources and analysis services make it difficult to connect and integrate these into interoperable workflows. To resolve this situation, we invited domain specialists from web service providers, client software developers, Open Bio* projects, the BioMoby project and researchers of emerging areas where a standard exchange data format is not well established, for an intensive collaboration entitled the BioHackathon 2008. The meeting was hosted by the Database Center for Life Science (DBCLS) and Computational Biology Research Center (CBRC) and was held in Tokyo from February 11th to 15th, 2008. In this report we highlight the work accomplished and the common issues arisen from this event, including the standardization of data exchange formats and services in the emerging fields of glycoinformatics, biological interaction networks, text mining, and phyloinformatics. In addition, common shared object development based on BioSQL, as well as technical challenges in large data management, asynchronous services, and security are discussed. Consequently, we improved interoperability of web services in several fields, however, further cooperation among major database centers and continued collaborative efforts between service providers and software developers are still necessary for an effective advance in bioinformatics web service technologies.

A method for full genome sequencing of all four serotypes of the dengue virus.

The availability of whole genome sequencing has contributed to many aspects of dengue research, and its use in dengue virus (DENV) surveillance for early epidemic warning has been proposed. Methods to sequence the genomes of individual dengue serotypes have been described previously, but no single method is known to be applicable for all four serotypes. This report describes a method for sequencing the entire genome of all four DENV serotypes. Using tagged oligonucleotide primers designed for the 3' end, viral RNA was reverse transcribed into a cDNA spanning the entire genome of each of the four serotypes (DENV-1 to -4). This was followed by amplification of the entire cDNA in five overlapping amplicons. A sequence tag was added to the sense primer annealing to the 5' UTR sequence and the antisense primer annealing to the 3' UTR sequence to ensure no terminal nucleotides were omitted during PCR. Sixty-one virus isolates were sequenced: 58 DENV-2, one DENV-1, one DENV-4 and one DENV-3 published previously. The method described could be applied readily for viral biology studies and incorporated into proactive dengue virologic surveillance.

Protein kinases as antibacterial targets.

The emergence of bacterial drug resistance highlights the need for new antibacterial targets. The role of protein kinases in signal transduction and cell regulation is ubiquitous. In spite of this the development of small molecule inhibitors of bacterial protein kinases has been slow, and no inhibitor has yet been successfully introduced to clinical use. In this review we focus on recent developments in inhibitors of the Histidine kinase family and pay particular attention to work on inhibiting the YycG Histidine kinase. We also highlight exciting new work in developing inhibitors for the eukaryote-like protein kinases of Mycobacterium tuberculosis including attempts to develop multi-target inhibitors.

Genomic epidemiology of a dengue virus epidemic in urban Singapore.

Dengue is one of the most important emerging diseases of humans, with no preventative vaccines or antiviral cures available at present. Although one-third of the world's population live at risk of infection, little is known about the pattern and dynamics of dengue virus (DENV) within outbreak situations. By exploiting genomic data from an intensively studied major outbreak, we are able to describe the molecular epidemiology of DENV at a uniquely fine-scaled temporal and spatial resolution. Two DENV serotypes (DENV-1 and DENV-3), and multiple component genotypes, spread concurrently and with similar epidemiological and evolutionary profiles during the initial outbreak phase of a major dengue epidemic that took place in Singapore during 2005. Although DENV-1 and DENV-3 differed in viremia and clinical outcome, there was no evidence for adaptive evolution before, during, or after the outbreak, indicating that ecological or immunological rather than virological factors were the key determinants of epidemic dynamics.

Peptide deformylase inhibitors of Mycobacterium tuberculosis: synthesis, structural investigations, and biological results.

Bacterial peptide deformylase (PDF) belongs to a subfamily of metalloproteases catalyzing the removal of the N-terminal formyl group from newly synthesized proteins. We report the synthesis and biological activity of highly potent inhibitors of Mycobacterium tuberculosis (Mtb) PDF enzyme as well as the first X-ray crystal structure of Mtb PDF. Structure-activity relationship and crystallographic data clarified the structural requirements for high enzyme potency and cell based potency. Activities against single and multi-drug-resistant Mtb strains are also reported.

Ontology-centric integration and navigation of the dengue literature.

Uninhibited access to the unstructured information distributed across the web and in scientific literature databases continues to be beyond the reach of scientists and health professionals. To address this challenge we have developed a literature driven, ontology-centric navigation infrastructure consisting of a content acquisition engine, a domain-specific ontology (in OWL-DL) and an ontology instantiation pipeline delivering sentences derived by domain-specific text mining. A visual query tool for reasoning over A-box instances in the populated ontology is presented and used to build conceptual queries that can be issued to the knowledgebase. We have deployed this generic infrastructure to facilitate data integration and knowledge sharing in the domain of dengue, which is one of the most prevalent viral diseases that continue to infect millions of people in the tropical and subtropical regions annually. Using our unique methodology we illustrate simplified search and discovery on dengue information derived from distributed resources and aggregated according to dengue ontology. Furthermore we apply data mining to the instantiated ontology to elucidate trends in the mentions of dengue serotypes in scientific abstracts since 1974.

Decision tree algorithms predict the diagnosis and outcome of dengue fever in the early phase of illness.

BACKGROUND: Dengue is re-emerging throughout the tropical world, causing frequent recurrent epidemics. The initial clinical manifestation of dengue often is confused with other febrile states confounding both clinical management and disease surveillance. Evidence-based triage strategies that identify individuals likely to be in the early stages of dengue illness can direct patient stratification for clinical investigations, management, and virological surveillance. Here we report the identification of algorithms that differentiate dengue from other febrile illnesses in the primary care setting and predict severe disease in adults. METHODS AND FINDINGS: A total of 1,200 patients presenting in the first 72 hours of acute febrile illness were recruited and followed up for up to a 4-week period prospectively; 1,012 of these were recruited from Singapore and 188 from Vietnam. Of these, 364 were dengue RT-PCR positive; 173 had dengue fever, 171 had dengue hemorrhagic fever, and 20 had dengue shock syndrome as final diagnosis. Using a C4.5 decision tree classifier for analysis of all clinical, haematological, and virological data, we obtained a diagnostic algorithm that differentiates dengue from non-dengue febrile illness with an accuracy of 84.7%. The algorithm can be used differently in different disease prevalence to yield clinically useful positive and negative predictive values. Furthermore, an algorithm using platelet count, crossover threshold value of a real-time RT-PCR for dengue viral RNA, and presence of pre-existing anti-dengue IgG antibodies in sequential order identified cases with sensitivity and specificity of 78.2% and 80.2%, respectively, that eventually developed thrombocytopenia of 50,000 platelet/mm(3) or less, a level previously shown to be associated with haemorrhage and shock in adults with dengue fever. CONCLUSION: This study shows a proof-of-concept that decision algorithms using simple clinical and haematological parameters can predict diagnosis and prognosis of dengue disease, a finding that could prove useful in disease management and surveillance.

Periodic re-emergence of endemic strains with strong epidemic potential-a proposed explanation for the 2004 Indonesian dengue epidemic.

Indonesia experienced a severe dengue epidemic in the first quarter of 2004 with 58,301 cases and 658 deaths reported to the WHO. All four dengue virus (DENV) serotypes were detected, with DENV-3 the predominant strain. To ascertain the molecular epidemiology of the DENV associated with the epidemic, complete genomes of 15 isolates were sequenced from patient serum collected in Jakarta during the epidemic, and two historical DENV-3 isolates from previous epidemics in 1988 and 1998 were selectively sequenced for comparative studies. Phylogenetic trees for all four serotypes indicate the viruses are endemic strains that have been circulating in Indonesia for a few decades. Whole-genome phylogeny showed the 2004 DENV-3 isolates share high similarity with those isolated in 1998 during a major epidemic in Sumatra. Together these subtype I DENV-3 strains form a Sumatran-Javan clade with demonstrated epidemic potential. No newly-acquired amino acid mutations were found while comparing genomes from the two epidemics. This suggests re-emergence of little-changed endemic strains as causative agents of the epidemic in 2004. Notably, the molecular evidence rules out change in the viral genomes as the trigger of the epidemic.

Host gene expression profiling of dengue virus infection in cell lines and patients.

BACKGROUND: Despite the seriousness of dengue-related disease, with an estimated 50-100 million cases of dengue fever and 250,000-500,000 cases of dengue hemorrhagic fever/dengue shock syndrome each year, a clear understanding of dengue pathogenesis remains elusive. Because of the lack of a disease model in animals and the complex immune interaction in dengue infection, the study of host response and immunopathogenesis is difficult. The development of genomics technology, microarray and high throughput quantitative PCR have allowed researchers to study gene expression changes on a much broader scale. We therefore used this approach to investigate the host response in dengue virus-infected cell lines and in patients developing dengue fever. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray and high throughput quantitative PCR method to monitor the host response to dengue viral replication in cell line infection models and in dengue patient blood samples, we identified differentially expressed genes along three major pathways; NF-kappaB initiated immune responses, type I interferon (IFN) and the ubiquitin proteasome pathway. Among the most highly upregulated genes were the chemokines IP-10 and I-TAC, both ligands of the CXCR3 receptor. Increased expression of IP-10 and I-TAC in the peripheral blood of ten patients at the early onset of fever was confirmed by ELISA. A highly upregulated gene in the IFN pathway, viperin, was overexpressed in A549 cells resulting in a significant reduction in viral replication. The upregulation of genes in the ubiquitin-proteasome pathway prompted the testing of proteasome inhibitors MG-132 and ALLN, both of which reduced viral replication. CONCLUSION/SIGNIFICANCE: Unbiased gene expression analysis has identified new host genes associated with dengue infection, which we have validated in functional studies. We showed that some parts of the host response can be used as potential biomarkers for the disease while others can be used to control dengue viral replication, thus representing viable targets for drug therapy.

DengueInfo: A web portal to dengue information resources.

DengueInfo (http://www.dengueinfo.org) is a web portal and database that brings clarity to dengue research by integrating the growing number of complete genome sequences of dengue virus with relevant literature and curated epidemiological information. Additionally, it represents a repository of on-going prospective and retrospective studies of dengue disease severity. We intend the database to be a flagship resource for the dengue community, providing standardized and high quality information and facilitating research into key aspects of dengue biology and assisting in its control. To aid this process we also introduce a standard nomenclature for dengue isolates inspired by globally accepted system used for influenza virus.

Establishment of a pipeline to analyse non-synonymous SNPs in Bos taurus.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are an abundant form of genetic variation in the genome of every species and are useful for gene mapping and association studies. Of particular interest are non-synonymous SNPs, which may alter protein function and phenotype. We therefore examined bovine expressed sequences for non-synonymous SNPs and validated and tested selected SNPs for their association with measured traits. RESULTS: Over 500,000 public bovine expressed sequence tagged (EST) sequences were used to search for coding SNPs (cSNPs). A total of 15,353 SNPs were detected in the transcribed sequences studied, of which 6,325 were predicted to be coding SNPs with the remaining 9,028 SNPs presumed to be in untranslated regions. Of the cSNPs detected, 2,868 were predicted to result in a change in the amino acid encoded. In order to determine the actual number of non-synonymous polymorphic SNPs we designed assays for 920 of the putative SNPs. These SNPs were then genotyped through a panel of cattle DNA pools using chip-based MALDI-TOF mass spectrometry. Of the SNPs tested, 29% were found to be polymorphic with a minor allele frequency >10%. A subset of the SNPs was genotyped through animal resources in order to look for association with age of puberty, facial eczema resistance or meat yield. Three SNPs were nominally associated with resistance to the disease facial eczema (P < 0.01). CONCLUSION: We have identified 15,353 putative SNPs in or close to bovine genes and 2,868 of these SNPs were predicted to be non-synonymous. Approximately 29% of the non-synonymous SNPs were polymorphic and common with a minor allele frequency >10%. Of the SNPs detected in this study, 99% have not been previously reported. These novel SNPs will be useful for association studies or gene mapping.

Recovering motifs from biased genomes: application of signal correction.

A significant problem in biological motif analysis arises when the background symbol distribution is biased (e.g. high/low GC content in the case of DNA sequences). This can lead to overestimation of the amount of information encoded in a motif. A motif can be depicted as a signal using information theory (IT). We apply two concepts from IT, distortion and patterned interference (a type of noise), to model genomic and codon bias respectively. This modeling approach allows us to correct a raw signal to recover signals that are weakened by compositional bias. The corrected signal is more likely to be discriminated from a biased background by a macromolecule. We apply this correction technique to recover ribosome-binding site (RBS) signals from available sequenced and annotated prokaryotic genomes having diverse compositional biases. We observed that linear correction was sufficient for recovering signals even at the extremes of these biases. Further comparative genomics studies were made possible upon correction of these signals. We find that the average Euclidian distance between RBS signal frequency matrices of different genomes can be significantly reduced by using the correction technique. Within this reduced average distance, we can find examples of class-specific RBS signals. Our results have implications for motif-based prediction, particularly with regards to the estimation of reliable inter-genomic model parameters.

Peptide deformylase inhibitors as potent antimycobacterial agents.

Peptide deformylase (PDF) catalyzes the hydrolytic removal of the N-terminal formyl group from nascent proteins. This is an essential step in bacterial protein synthesis, making PDF an attractive target for antibacterial drug development. Essentiality of the def gene, encoding PDF from Mycobacterium tuberculosis, was demonstrated through genetic knockout experiments with Mycobacterium bovis BCG. PDF from M. tuberculosis strain H37Rv was cloned, expressed, and purified as an N-terminal histidine-tagged recombinant protein in Escherichia coli. A novel class of PDF inhibitors (PDF-I), the N-alkyl urea hydroxamic acids, were synthesized and evaluated for their activities against the M. tuberculosis PDF enzyme as well as their antimycobacterial effects. Several compounds from the new class had 50% inhibitory concentration (IC50) values of <100 nM. Some of the PDF-I displayed antibacterial activity against M. tuberculosis, including MDR strains with MIC90 values of <1 microM. Pharmacokinetic studies of potential leads showed that the compounds were orally bioavailable. Spontaneous resistance towards these inhibitors arose at a frequency of < or =5 x 10(-7) in M. bovis BCG. DNA sequence analysis of several spontaneous PDF-I-resistant mutants revealed that half of the mutants had acquired point mutations in their formyl methyltransferase gene (fmt), which formylated Met-tRNA. The results from this study validate M. tuberculosis PDF as a drug target and suggest that this class of compounds have the potential to be developed as novel antimycobacterial agents.