In many laboratory visuo-motor decision tasks, subjects compensate for their own visuo-motor error, earning close to the maximum reward possible. To do so, they must combine information about the distribution of possible error with values associated with different movement outcomes. The optimal solution is a potentially difficult computation that presupposes knowledge of the probability density function (pdf) of visuo-motor error associated with each possible planned movement. It is unclear how the brain represents such pdfs or computes with them. In three experiments, we used a forced-choice method to reveal subjects' internal representations of their spatial visuo-motor error in a speeded reaching movement. Although subjects' objective distributions were unimodal, close to Gaussian, their estimated internal pdfs were typically multimodal and were better described as mixtures of a small number of distributions differing only in location and scale. Mixtures of a small number of uniform distributions outperformed other mixture distributions, including mixtures of Gaussians.

BACKGROUND

Ontologies and taxonomies have proven highly beneficial for biocuration. The Open Biomedical Ontology (OBO) Foundry alone lists over 90 ontologies mainly built with OBO-Edit. Creating and maintaining such ontologies is a labour-intensive, difficult, manual process. Automating parts of it is of great importance for the further development of ontologies and for biocuration.

RESULTS

We have developed the Dresden Ontology Generator for Directed Acyclic Graphs (DOG4DAG), a system which supports the creation and extension of OBO ontologies by semi-automatically generating terms, definitions and parent-child relations from text in PubMed, the web and PDF repositories. DOG4DAG is seamlessly integrated into OBO-Edit. It generates terms by identifying statistically significant noun phrases in text. For definitions and parent-child relations it employs pattern-based web searches. We systematically evaluate each generation step using manually validated benchmarks. The term generation leads to high-quality terms also found in manually created ontologies. Up to 78% of definitions are valid and up to 54% of child-ancestor relations can be retrieved. There is no other validated system that achieves comparable results. By combining the prediction of high-quality terms, definitions and parent-child relations with the ontology editor OBO-Edit we contribute a thoroughly validated tool for all OBO ontology engineers.

BACKGROUND

DOG4DAG is available within OBO-Edit 2.1 at http://www.oboedit.org.

BACKGROUND

Supplementary data are available at Bioinformatics online.

Doppler echocardiographic studies of transmitral flow have become a routine clinical tool for the assessment and characterization of ventricular diastolic (filling) function. We have previously derived a parametrized diastolic filling (PDF) formalism for the purpose of diastolic function assessment using Doppler echocardiography. The model accommodates the mechanical "suction" feature of early diastolic filling of the heart by using a simple harmonic oscillator (SHO) as a paradigm for the kinematics of filling. PDF model predictions of transmitral flow velocity have shown excellent agreement with human echocardiographic Doppler contours (temporal profiles) when a visual, transparency overlay method of model fit to clinical Doppler contour comparison was used. The determination of PDF model parameters from the clinical Doppler contour is equivalent to the solution of the "inverse problem" of diastole. Previously, this determination consisted of a manual, iterative method of graphical overlay, in which model predicted contours were visually compared with the echocardiography machine generated Doppler contour using transparencies. To automate the process of model parameter estimation (i.e., solution of the "inverse problem") for the early or "rapid filling" phase of diastole (known in cardiology as the E-wave of the clinical Doppler velocity profile [DVP]) we recorded the acoustic pulsed Doppler signal using the forward channel of a commercial echocardiography machine. The Doppler spectrogram for a particular E-wave was recreated using short-time Fourier transform processing. The maximum velocity envelope (MVE) was extracted from the spectrogram. The PDF model was fit to the E-wave MVE using a Levenberg-Marquardt (iterative) algorithm by the requirement that the mean-square error between the clinical data (MVE) and the model be minimized. Because the model is linear, all of the PDF parameters for the Doppler E-wave can be uniquely determined. We show that: (1) solution of the "inverse problem of diastole" is possible; (2) clinical Doppler E-wave contours can be accurately reproduced and quantified using the PDF formalism and its parameters; and (3) our proposed, automated method of PDF parameter determination for the E-wave is robust.

Divergence measures provide a means to measure the pairwise dissimilarity between "objects," e.g., vectors and probability density functions (pdfs). Kullback-Leibler (KL) divergence and the square loss (SL) function are two examples of commonly used dissimilarity measures which along with others belong to the family of Bregman divergences (BD). In this paper, we present a novel divergence dubbed the Total Bregman divergence (TBD), which is intrinsically robust to outliers, a very desirable property in many applications. Further, we derive the TBD center, called the t-center (using the l(1)-norm), for a population of positive definite matrices in closed form and show that it is invariant to transformation from the special linear group. This t-center, which is also robust to outliers, is then used in tensor interpolation as well as in an active contour based piecewise constant segmentation of a diffusion tensor magnetic resonance image (DT-MRI). Additionally, we derive the piecewise smooth active contour model for segmentation of DT-MRI using the TBD and present several comparative results on real data.

In early 2006, the National Institute for Occupational Safety and Health created a field research team whose mission is to visit a variety of facilities engaged in the production, handling, or use of engineered nanomaterials (ENMs) and to conduct initial emission and exposure assessments to identify candidate sites for further study. To conduct the assessments, the team developed the Nanoparticle Emission Assessment Technique (NEAT), which has been used at numerous facilities to sample multiple engineered nanomaterials. Data collected at four facilities, which volunteered to serve as test sites, indicate that specific tasks can release ENMs to the workplace atmosphere and that traditional controls such as ventilation can be used to limit exposure. Metrics such as particle number concentration (adjusted for background), airborne mass concentration, and qualitative transmission electron microscopy were used to determine the presence, nature, and magnitude of emissions and whether engineered nanomaterials migrated to the workers' breathing zone. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a PDF file containing information on facilities, a description of processes/tasks, existing controls, and sampling strategy, and a PDF file containing TEM images according to facility and task.].

In the probability density function (PDF) approach to neural network modeling, a common simplifying assumption is that the arrival times of elementary postsynaptic events are governed by a Poisson process. This assumption ignores temporal correlations in the input that sometimes have important physiological consequences. We extend PDF methods to models with synaptic event times governed by any modulated renewal process. We focus on the integrate-and-fire neuron with instantaneous synaptic kinetics and a random elementary excitatory postsynaptic potential (EPSP), A. Between presynaptic events, the membrane voltage, v, decays exponentially toward rest, while s, the time since the last synaptic input event, evolves with unit velocity. When a synaptic event arrives, v jumps by A, and s is reset to zero. If v crosses the threshold voltage, an action potential occurs, and v is reset to v(reset). The probability per unit time of a synaptic event at time t, given the elapsed time s since the last event, h(s, t), depends on specifics of the renewal process. We study how regularity of the train of synaptic input events affects output spike rate, PDF and coefficient of variation (CV) of the interspike interval, and the autocorrelation function of the output spike train. In the limit of a deterministic, clocklike train of input events, the PDF of the interspike interval converges to a sum of delta functions, with coefficients determined by the PDF for A. The limiting autocorrelation function of the output spike train is a sum of delta functions whose coefficients fall under a damped oscillatory envelope. When the EPSP CV, sigma A/mu A, is equal to 0.45, a CV for the intersynaptic event interval, sigma T/mu T = 0.35, is functionally equivalent to a deterministic periodic train of synaptic input events (CV = 0) with respect to spike statistics. We discuss the relevance to neural network simulations.

We used real-time imaging to detect cAMP levels in neurons of intact fly brains to study the mechanisms of circadian pacemaker synchronization by the neuropeptide pigment dispersing factor (PDF) in Drosophila. PDF receptor (PDF-R) is expressed by both M (sLNv) and E (LNd) pacemaker subclasses and is coupled to G(sα) in both cases. We previously reported that PDF-R in M pacemakers elevates cAMP levels by activating the ortholog of mammalian adenylate cyclase 3 (AC3) but that AC3 disruptions had no effect on E pacemaker sensitivity to PDF. Here, we show that PDF-R in E pacemakers activates a different AC isoform, AC78C, an ortholog of mammalian AC8. Knockdown of AC78C by transgenic RNAi substantially reduces, but does not completely abrogate, PDF responses in these E pacemakers. The knockdown effect is intact when restricted to mature stages, suggesting a physiological and not a development role for AC78C in E pacemakers. The AC78C phenotype is rescued by the overexpression of AC78C but not by overexpression of the rutabaga AC. AC78C overexpression does not disrupt PDF responses in these E pacemakers, and neither AC78C knockdown nor its overexpression disrupted locomotor rhythms. Finally, knockdown of 2 AKAPs, nervy and AKAP200, partially reduces LNd PDF responses. These findings begin to identify the components of E pacemaker PDF-R signalosomes and indicate that they are distinct from PDF-R signalosomes in M pacemakers: we propose they contain AC78C and at least 1 other AC.

Hypotheses previously used (Blair, 1932) in deriving formulae for stimulation by direct currents are applied to other forms of electrical stimuli. This consists in considering solutions of the equation See PDF for Structure. where p is assumed to represent the local excitatory process, V is the voltage of the stimulus and K and k are constants. The solutions are discussed in regard to condenser discharges, linearly rising currents, exponentially rising currents, and alternating currents. New experimental work with alternating currents of frequencies above 400 per second on the sciatic gastrocnemius of the frog is related to the formulae.

The Dragon Exploration System for Toxicants and Fertility (DESTAF) is a publicly available resource which enables researchers to efficiently explore both known and potentially novel information and associations in the field of reproductive toxicology. To create DESTAF we used data from the literature (including over 10500 PubMed abstracts), several publicly available biomedical repositories, and specialized, curated dictionaries. DESTAF has an interface designed to facilitate rapid assessment of the key associations between relevant concepts, allowing for a more in-depth exploration of information based on different gene/protein-, enzyme/metabolite-, toxin/chemical-, disease- or anatomically centric perspectives. As a special feature, DESTAF allows for the creation and initial testing of potentially new association hypotheses that suggest links between biological entities identified through the database. DESTAF, along with a PDF manual, can be found at http://cbrc.kaust.edu.sa/destaf. It is free to academic and non-commercial users and will be updated quarterly.

Based on experimental work and clinical small studies, histidine-tryptophan-ketoglutarate (HTK) solution was found to be suitable not only for heart and kidney preservation but also for liver preservation. We decided, therefore, to use this preservation solution for clinical liver preservation in a prospective multi-centre trial. Enrolment to the study was from 1996 to 1999 in four European centres, and the results of 214 patients with HTK-preserved organs were analysed. Analysis showed a primary dysfunction (PDF) rate of 8.8%, with a primary non-function (PNF) rate of 2.3% and initial poor function (IPF) in 6.5%. Patient survival rate at 1 year was 83% and 1-year graft survival rate was 80%. In a univariate and a multivariate analysis PDF, early surgical complications and tendentiously severe infections (septicaemia, pneumonia, cholangitis) were identified as independent risk factors for graft and patient survival. Preservation with HTK can be regarded as an established alternative to preservation with University of Wisconsin (UW) solution when preservation times are short. Definitive assessment of the efficacy of preservation solutions requires further prospective randomised clinical trials that compare HTK and UW.

A peptide-cleaving catalyst selective for peptide deformylase (PDF) was obtained from a library containing about 15 000 catalyst candidates. The catalyst cleaved the polypeptide backbone of PDF at Gln(152)-Arg(153). Docking simulations suggested multiple modes of interactions in the complex formed between the catalyst and PDF.

OBJECTIVE

Pharmacokinetic (PK) interindividual variability in amikacin has been shown to be wide in neonates. This study evaluated the evolution of this variability with gestational age (GA) at birth in relation to renal maturation.

METHODS

Population PK values of amikacin were studied in 131 newborns (postnatal age 1 day, GA 24-41 weeks) divided into 16 groups, defined by GA, from 24 to 41 weeks (with a mean of 8.2 infants per group). PK variables were Kel/Vol, Ks/Vs, Cl/Vol. Cls/ where: Kel = Kslope x GA + Kintercept, Cl = Clslope x GA + Clintercept, and Vol = Vs x body weight. Ki and Cli were held as constants. The nonparametric distribution of the probability density function (PDF) was obtained, as were mean, median, and SD values of each PK variable for each GA group.

RESULTS

Amikacin elimination increased linearly with GA, showing that GA is a good covariate of renal elimination. Amikacin volume of distribution increased with body weight up to a GA of about 38 weeks and then decreased for highest GA values. However, the PDF for the individual GA groups showed a multimodal PK distribution. Kel, Vol, Vs, Cl, and Cl, standard deviations increased linearly with GA, showing differential renal maturation. The higher the GA, the more interindividual PK variability increased.

CONCLUSIONS

These results show that amikacin elimination and the volume of distribution are dependent upon GA, and that differential renal maturation in neonates is responsible for the wider PK interindividual variability with high GA. Dosage regimens of amikacin and other aminoglycosides should be revised in newborns with high GA. Bayesian adaptive control of therapeutics might be particularly indicated to obtain efficacy for each neonate as early as the first dose.

Pigment-dispersing factor (PDF) is well known as a circadian clock output factor, which drives daily activity rhythms in many insects. The role of its homologue, pigment-dispersing hormone (PDH), in the regulation of circadian and/or circatidal rhythmicity in crustaceans is, however, poorly understood. The intertidal isopod crustacean, Eurydice pulchra has well-defined circatidal (12.4-hour) activity rhythms. In this study we show that this runs parallel to a circadian (24-hour) cycle of chromatophore dispersion. As a first step in determining the potential role of PDH in these rhythms, we have identified a novel form of PDH expressed in this species. Because conventional homology cloning was unsuccessful, we employed immuno-identification and Edman microsequencing to determine the primary structure of this peptide. From this, cDNA cloning identified the nucleotide encoding sequence and thus facilitated description of PDH neurons by in situ hybridization and immunohistochemistry. We show them to be morphologically similar to those that co-ordinate circadian activity rhythms in insects. In animals expressing both tidal (activity) and circadian (chromatophore) rhythms, however, there was no evidence for a corresponding periodicity in the expression of pdh transcript, as determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in Eurydice heads. It is therefore suggested that any role for PDH in daily/tidal timing in Eurydice is not mediated at the transcriptional level, rather rhythms in neurohemal release may be important in such co-ordination.

The activities of six peptide deformylase (PDF) inhibitors against 107 respiratory tract pathogens were studied and compared to those of ciprofloxacin and amoxicillin-clavulanate. Against Streptococcus pneumoniae, BB-83698 and BB-83815 were the most active PDF inhibitors (MIC at which 90% of the organisms tested were inhibited [MIC(90)], 0.25 microg/ml). Five of the agents showed similar activity against Moraxella catarrhalis (MIC(90), 0.12 microg/ml). All PDF inhibitors were less active against Haemophilus influenzae; BB-3497 was the most active agent (MIC(90), 2 microg/ml). Five agents were studied against Chlamydia spp. and showed activity similar to that of ciprofloxacin (MIC, 0.5 to 4 microg/ml). This study demonstrates that PDF inhibitors have the potential to be developed for the treatment of respiratory tract infections.

Polypeptide deformylase (<em>PDF</em>) is an essential bacterial metalloenzyme responsible for the removal of the N-formyl group from the N-terminal methionine of nascent polypeptides. Inhibition of bacterial <em>PDF</em> enzymes by actinonin, a naturally occurring antibacterial agent, has been characterized using steady-state and transient kinetic methods. Slow binding of actinonin to these enzymes is observed under steady-state conditions. Progress curve analysis is consistent with a two-step binding mechanism, in which tightening of the initial encounter complex (EI) results in a final complex (EI*) with an extremely slow, but observable, off-rate (t(1/2) for inhibitor dissociation>>or=0.77 days). Stopped-flow measurement of <em>PDF</em> fluorescence confirms formation of EI and provides a direct measurement of the association rate. Rapid dilution studies establish that the potency of actinonin is enhanced by more than 2000-fold upon tightening of EI to form EI*, from K(i) = 530 nM (EI) to Ki*<or= 0.23 nM (EI*). In sharp contrast, the previously reported small molecule <em>PDF</em> inhibitor, SB-543668, is a competitive, readily reversible inhibitor (t(1/2) for dissociation = 2.8 s). In addition, we demonstrate that BB-3497 is also a time-dependent inhibitor of <em>PDF</em> with an extremely slow off-rate. The two-step inhibition model detailed herein for the inhibition of Staphylococcus aureus <em>PDF</em> by actinonin and BB-3497 is consistent with a recent report on the time-dependent inhibition of Escherichia coli <em>PDF</em> by a macrocyclic peptidomimetic inhibitor [Ngugen, K. T., et al. (2004) Bioorg. Chem. 32, 178-191]. This study substantially extends our understanding of <em>PDF</em> inhibition and may facilitate the development of novel antibiotics.

BACKGROUND

In this paper, we present a novel framework for inferring regulatory and sequence-level information from gene co-expression networks. The key idea of our methodology is the systematic integration of network inference and network topological analysis approaches for uncovering biological insights.

RESULTS

We determine the gene co-expression network of Bacillus subtilis using Affymetrix GeneChip time-series data and show how the inferred network topology can be linked to sequence-level information hard-wired in the organism's genome. We propose a systematic way for determining the correlation threshold at which two genes are assessed to be co-expressed using the clustering coefficient and we expand the scope of the gene co-expression network by proposing the slope ratio metric as a means for incorporating directionality on the edges. We show through specific examples for B. subtilis that by incorporating expression level information in addition to the temporal expression patterns, we can uncover sequence-level biological insights. In particular, we are able to identify a number of cases where (1) the co-expressed genes are part of a single transcriptional unit or operon and (2) the inferred directionality arises due to the presence of intra-operon transcription termination sites.

BACKGROUND

The software will be provided on request.

BACKGROUND

http://www.phys.psu.edu/~ralbert/pdf/gma_bioinf_supp.pdf

BACKGROUND

Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine.

RESULTS

We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA)-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework.

CONCLUSIONS

GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

A new method is presented for the generation of stochastic (random) sequences with an arbitrarily specified first-order probability distribution function (PDF) and an arbitrarily specified first-order auto-correlation function (ACF). A set of numbers with the desired PDF are first generated. These are then given a white (independent) ACF by double stochastic interchange. The desired ACF is then obtained by stochastically shuffling the series to minimize a sum of squares criterion between desired and actual ACFs. The technique is particularly useful for generating experimental stimuli for system identification, sequences for numerical stimulation, and test series for evaluating signal processing algorithms when colored (non-white) non-Gaussian data are required.

The tests presented in Tables I, II, and III show that only in the higher concentration cross reactions do take place, and that there is definite specificity of the two sorts of immune sera for the homologous antigens. Thus it is easy to differentiate the l- and d-antigens in dilutions 1:100 and upwards. The occurrence of cross reactions can readily be ascribed to the fact that the l- and d-acids present in the two antigens are identical in every respect but the position of the groups connected with the asymetric carbon atom. The i-antigen reacts with both sorts of immune sera as could be expected since it must consist of a mixture of equal parts of l- and d-antigen. The reactions of the i-antigen appear to be only slightly weaker than those of the homologous ones owing to the fact that the intensity of the reactions diminishes but slowly with increasing dilution of the antigens. It is also to be considered that small differences cannot be judged very accurately. Tests with two l- and four d-immune sera not recorded in the tables confirmed the results already discussed. Considering that ferments are known to be adapted ordinarily to one type of steric isomers it may be worth noting that antibodies were formed by the same species of animals for optical antipodes. From the results summarized in Tables IV,a and IV,b one sees that the l- and d-immune sera also differentiate clearly between the l- and d-acids when they are not diazotized and not combined with protein. The l-acid inhibits much more the precipitation of the l-antigen by the homologous immune serum than the d-acid and the converse effect occurs if the inhibiting action is tested on the precipitation of d-antigen by d-immune serum. The inactive phenyl (para-aminobenzoylamino) acetic acid behaved in such tests as a mixture of l- and d-acids, i.e., it acted markedly in both cases, more than the heterologous and less than the homologous acid. The experiments reported bring a definite proof for the view that the steric configuration of antigenic groups is one of the factors determining serological specificity. In the particular case under consideration the mere difference in the position of H and COOH as indicated in the following formulas sufficed to alter the reactivity. See PDF for Equation. The fact that steric isomers are acted upon selectively by immune sera may be supposed to play a significant part in the serological specificity of carbohydrates such as those discovered in bacterial antigens.

We investigated the diurnal oscillation in abundance of the catalytic α subunit of the sodium/potassium pump (ATPα) in the brain of Drosophila melanogaster. This rhythm is bimodal and is particularly robust in the glia cells of the lamina, the first optic neuropil. We observed loss of ATPα cycling in lamina glia in behaviourally arrhythmic per(01) and tim(01) mutants and in flies overexpressing the pro-apoptotic gene hid in the PDF-positive clock neurons. Moreover, the rhythm of ATPα abundance was altered in cry(01) and Pdf(0) mutants, in flies with a weakened clock mechanism in retina photoreceptor cells and in those subject to downregulation of the neuropeptide ITP by RNAi. This complex, rhythmic regulation of the α subunit suggests that the sodium/potassium pump may be a key target of the circadian pacemaker to impose daily control on brain activities, such as rhythmic changes in neuronal plasticity, which are best observed in the visual system.

Following Mandelbrot's theory of fractals, the area-perimeter relation is used to investigate the geometry of satellite- and radar-determined cloud and rain areas between 1 and 1.2 x 10(6) square kilometers. The data are well fit by a formula in which the perimeter is given approximately by the square root of the area raised to the power D [See equation in the PDF], where D is interpreted as the fractal dimension of the perimeter. It is concluded that rain and cloud perimeters are fractals-they have no characteristic horizontal length scale between 1 and 1000 kilometers.

1. During paralysis, the brain of the mouse infected with poliomyelitis virus shows on test after mincing a decrease in anaerobic glycolysis with no significant change in oxygen utilization. The decrease in anaerobic glycolysis varies from 5 per cent to 50 per cent. 2. Sodium fluoride produces a greater inhibition of anaerobic glycolysis in normal than in poliomyelitic brain. 3. Dehydrogenase activity is higher for poliomyelitis-infected brain without added substrate. This difference from normal disappears when substrates are added. 4. The ratio of See PDF for Equation for the sliced motor cortex is higher than for sliced visual cortex of the dog and cat. 5. The oxygen consumption of the anterior horn of the sliced spinal cord of dog and cat is much less than that of the cerebral cortex. 6. The findings are in keeping with the view that, at a certain stage of the infection, the nerve cells may be reversibly injured but not yet destroyed by the virus.

GSK1322322 is the first in a new class of antibiotics that targets peptide deformylase (PDF), an essential bacterial enzyme required for protein maturation. This randomized, double-blind, placebo-controlled, eight-cohort phase I trial enrolled 62 healthy volunteers to assess safety, tolerability, and pharmacokinetic profiles of GSK1322322. GSK1322322 was administered as a single oral or intravenous (IV) dose, escalating from 500 to 3,000 mg or repeat IV doses escalating from 500 to 1,500 mg twice daily. Upon repeat IV administration, GSK1322322 exhibits linear pharmacokinetics over time upon repeat doses as shown by time-invariant pharmacokinetics. A dose-proportional increase in area under concentration-time curve was observed after single or repeat IV dosing, whereas clearance at steady state remained generally unchanged across doses. There was minimal accumulation of GSK1322322 after repeat IV twice-daily administration. After oral tablet doses of GSK1322322 1,000 and 1,500 mg, absolute bioavailability was 69% and 56%, respectively. GSK1322322 administration at single and repeat IV doses and at supratherapeutic single IV doses of 2,000 and 3,000 mg was associated with mild-to-moderate drug-related adverse events. On the basis of the pharmacokinetics and tolerability demonstrated in this study, GSK1322322 has the potential to become the first-in-class PDF inhibitor for clinical use.

Chlamydia trachomatis, an obligate intracellular bacterium, is a highly prevalent human pathogen. Hydroxamic-acid-based matrix metalloprotease inhibitors can effectively inhibit the pathogen both in vitro and in vivo, and have exhibited therapeutic potential. Here, we provide genome sequencing data indicating that peptide deformylase (PDF) is the sole target of the inhibitors in this organism. We further report molecular mechanisms that control chlamydial PDF (cPDF) expression and inhibition efficiency. In particular, we identify the σ⁶⁶-dependent promoter that controls cPDF gene expression and demonstrate that point mutations in this promoter lead to resistance by increasing cPDF transcription. Furthermore, we show that substitution of two amino acids near the active site of the enzyme alters enzyme kinetics and protein stability.