Kinematics of intracellular chlamydiae provide evidence for contact-dependent development.
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ABSTRACT:
SUBMITTER: Wilson DP
PROVIDER: S-EPMC2737980 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chlamydiae are obligate intracellular bacteria comprising important human pathogens and symbionts of protists. Molecular evidence indicates a tremendous diversity of chlamydiae particularly in marine environments, yet our current knowledge is based mainly on terrestrial representatives. Here we provide first insights into the biology of marine chlamydiae representing three divergent clades. Our analysis of single-cell amplified genomes revealed hallmarks of the chlamydial lifestyle, supporting the ancient origin of their characteristic developmental cycle and major virulence mechanisms. Surprisingly, these chlamydial genomes encode a complete flagellar apparatus, a previously unreported feature. We show that flagella are an ancient trait that was subject to differential gene loss among extant chlamydiae. Together with a chemotaxis system, these marine chlamydiae are likely motile, with flagella potentially playing a role during host cell infection. This study broadens our view on chlamydial biology and indicates a largely underestimated potential to adapt to different hosts and environments.
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Project description:This study was to investigate the in vivo tibiofemoral cartilage contact locations before and after anterior cruciate ligament (ACL) reconstruction at 6 and 36 months. Ten patients with unilateral ACL injury were included. A step-up motion was analyzed using a combined magnetic resonance modeling and dual fluoroscopic imaging techniques. The preoperative (i.e. ACL deficient and healthy contralateral) and postoperative cartilage contact locations at 6 and 36 months were analyzed. Similar patterns of the cartilage contact locations during the step-up motion were found for the preoperative and postoperative knee states as compared to the preoperative healthy contralateral side. At the end of step-up motion, the medial contact locations at postoperative 36 months were more anterior when compared to the preoperative healthy contralateral (p=0.02) and 6 months postoperative knee states (p=0.01). The changes of the cartilage contact locations at 36 months after ACL reconstruction compared to the healthy contralateral side were strongly correlated with the changes at 6 months postoperatively. This study showed that the tibiofemoral cartilage contact locations of the knee changes with time after ACL reconstruction, implying an ongoing recovery process within the 36 months after the surgery. There could be an association between the short-term (6 months) and longer-term (36 months) contact kinematics after ACL reconstruction. Future studies need to investigate the intrinsic relationship between knee kinematics at different times after ACL reconstruction.
| S-EPMC5074869 | biostudies-literature
Project description:MicroRNAs (miRs) are a large class of small regulatory RNAs that function as nodes of signaling networks. This implicates that miRs expression has to be finely tuned, as observed during cell cycle progression. Here, using an expression profiling approach, we provide evidence that the CDK inhibitor p27Kip1 regulates miRs expression following cell cycle exit. By using wild type and p27KO cells harvested in different phases of the cell cycle we identified several miRs regulated by p27Kip1 during the G1 to S phase transition. Among these miRs, we identified miR-223 as a miR specifically upregulated by p27Kip1 in G1 arrested cells. Our data demonstrate that p27Kip1 regulated the expression of miR-223, via two distinct mechanisms. p27Kip1 directly stabilized mature miR-223 expression, acting as a RNA binding protein and it controlled E2F1 expression that, in turn, regulated miR-223 promoter activity. The resulting elevated miR-223 levels ultimately participated to arresting cell cycle progression following contact inhibition. Importantly, this mechanism of growth control was conserved in human cells and deranged in breast cancers. Here, we identify a novel and conserved function of p27Kip1 that, by modulating miR-223 expression, contributes to proper regulation of cell cycle exit following contact inhibition. Thus we propose a new role for miR-223 in the regulation of breast cancer progression.
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Project description:ATP/ADP translocases catalyze the highly specific transport of ATP across a membrane in an exchange mode with ADP. Such unique transport proteins are employed by plant plastids and have among the prokaryotes so far only been identified in few obligate intracellular bacteria belonging to the Chlamydiales and the Rickettsiales. In this study, 12 phylogenetically diverse bacterial endosymbionts of free-living amoebae and paramecia were screened for the presence of genes encoding ATP/ADP transport proteins. The occurrence of ATP/ADP translocase genes was found to be restricted to endosymbionts related to rickettsiae and chlamydiae. We showed that the ATP/ADP transport protein of the Parachlamydia-related endosymbiont of Acanthamoeba sp. strain UWE25, a recently identified relative of the important human pathogens Chlamydia trachomatis and Chlamydophila pneumoniae, is functional when expressed in the heterologous host Escherichia coli and demonstrated the presence of transcripts during the chlamydial developmental cycle. These findings indicate that the interaction between Parachlamydia-related endosymbionts and their amoeba hosts concerns energy parasitism similar to the interaction between pathogenic chlamydiae and their human host cells. Phylogenetic analysis of all known ATP/ADP translocases indicated that the genes encoding ATP/ADP translocases originated from a chlamydial ancestor and were, after an ancient gene duplication, transferred horizontally to rickettsiae and plants.
| S-EPMC321502 | biostudies-literature
Project description:Novel chlamydiae are newly recognized members of the phylum Chlamydiales that are only distantly related to the classic Chlamydiaceae, i.e., Chlamydia and Chlamydophila species. They also exhibit an obligate biphasic intracellular life cycle within eukaryote host cells. Some of these new chlamydiae are currently considered potential emerging human and/or animal pathogens. Parachlamydia acanthamoebae and Simkania negevensis are both emerging respiratory human pathogens, Waddlia chondrophila could be a novel abortigenic bovine agent, and Piscichlamydia salmonis has recently been identified as an agent of the gill epitheliocystis in the Atlantic salmon. Fritschea spp. and Rhabdochlamydia spp. seem to be confined to arthropods, but some evidence for human exposure exists. In this review, we first summarize the data supporting a pathogenic potential of the novel chlamydiae for humans and other vertebrates and the interactions that most of these chlamydiae have with free-living amoebae. We then review the diagnostic approaches to infections potentially due to the novel chlamydiae, especially focusing on the currently available PCR-based protocols, mammalian cell culture, the amoebal coculture system, and serology.
| S-EPMC1471994 | biostudies-literature
Project description:Gene transcription in bacteria is carried out by the multisubunit RNA polymerase (RNAP), which is composed of a catalytic core enzyme and a promoter-recognizing σ factor. The core enzyme comprises two α subunits, one β subunit, one β' subunit, and one ω subunit. The ω subunit plays critical roles in the assembly of the core enzyme and other cellular functions, including the regulation of bacterial growth, the stress response, and biofilm formation. However, the identity of an ω subunit for the obligate intracellular bacterium Chlamydia has not previously been determined. Here, we report the identification of the hypothetical protein CTL0286 as the probable chlamydial ω subunit based on sequence, synteny, and AlphaFold and AlphaFold-Multimer three-dimensional-structure predictions. Our findings indicate that CTL0286 functions as the missing ω subunit of chlamydial RNAP. Our extended analysis also indicates that all obligate intracellular bacteria have ω orthologs. IMPORTANCE Chlamydiae are obligate intracellular bacteria that replicate only inside eukaryotic cells. Previously, it has not been possible to identify a candidate gene encoding the chlamydial RNA polymerase ω subunit, and it has been hypothesized that the chlamydial RNA polymerase ω subunit was lost in the evolutionary process through which Chlamydiae reduced their genome size and proteome sizes to adapt to an obligate intracellular lifestyle. Here, we report the identification of the chlamydial RNA polymerase ω subunit, based on conserved sequence, conserved synteny, AlphaFold-predicted conserved three-dimensional structure, and AlfaFold-Multimer-predicted conserved interactions. Our identification of the previously elusive chlamydial RNA polymerase ω subunit sets the stage for investigation of its roles in regulation of gene expression during chlamydial growth, development, and stress responses, and sets the stage for preparation and study of the intact chlamydial RNA polymerase and its interactions with inhibitors.
| S-EPMC9973325 | biostudies-literature
Project description:The PVC superphylum is an amalgamation of species from the phyla Planctomycetes, Verrucomicrobia, and Chlamydiae, along with the Lentisphaerae, Poribacteria, and two other candidate divisions. The diverse species of this superphylum lack any significant marker that differentiates them from other bacteria. Recently, genome sequences for 37 species covering all of the main PVC groups of bacteria have become available. We have used these sequences to construct a phylogenetic tree based upon concatenated sequences for 16 proteins and identify molecular signatures in protein sequences that are specific for the species from these phyla or those providing molecular links among them. Of the useful molecular markers identified in the present work, six conserved signature indels (CSIs) in the proteins Cyt c oxidase, UvrD helicase, urease, and a helicase-domain containing protein are specific for the species from the Verrucomicrobia phylum; three other CSIs in an ABC transporter protein, cobyrinic acid ac-diamide synthase, and SpoVG protein are specific for the Planctomycetes species. Additionally, a 3 aa insert in the RpoB protein is uniquely present in all sequenced Chlamydiae, Verrucomicrobia, and Lentisphaerae species, providing evidence for the shared ancestry of the species from these three phyla. Lastly, we have also identified a conserved protein of unknown function that is exclusively found in all sequenced species from the phyla Chlamydiae, Verrucomicrobia, Lentisphaerae, and Planctomycetes suggesting a specific linkage among them. The absence of this protein in Poribacteria, which branches separately from other members of the PVC clade, indicates that it is not specifically related to the PVC clade of bacteria. The molecular markers described here in addition to clarifying the evolutionary relationships among the PVC clade of bacteria also provide novel tools for their identification and for genetic and biochemical studies on these organisms.
| S-EPMC3444138 | biostudies-literature
Project description:Analysis of polyethylene component wear and implant loosening in total knee arthroplasty (TKA) requires precise knowledge of in vivo articular motion and loading conditions. This study presents a simultaneous in vivo measurement of tibiofemoral articular contact forces and contact kinematics in three TKA patients. These measurements were accomplished via a dual fluoroscopic imaging system and instrumented tibial implants, during dynamic single leg lunge and chair rising-sitting. The measured forces and contact locations were also used to determine mediolateral distribution of axial contact forces. Contact kinematics data showed a medial pivot during flexion of the knee, for all patients in the study. Average axial forces were higher for lunge compared to chair rising-sitting (224% vs. 187% body weight). In this study, we measured peak anteroposterior and mediolateral forces averaging 13.3% BW during lunge and 18.5% BW during chair rising-sitting. Mediolateral distributions of axial contact force were both patient and activity specific. All patients showed equitable medial-lateral loading during lunge but greater loads at the lateral compartment during chair rising-sitting. The results of this study may enable more accurate reproduction of in vivo loads and articular motion patterns in wear simulators and finite element models. This in turn may help advance our understanding of factors limiting longevity of TKA implants, such as aseptic loosening and polyethylene component wear, and enable improved TKA designs.
| S-EPMC3177238 | biostudies-literature
Project description:BackgroundLateral meniscus transplantation is a proven treatment option for the meniscus-deficient knee, yet little is known about meniscal kinematics, strain, and tibiofemoral contact pressure changes after transplantation or the effect of altered root position in lateral meniscus transplantation.PurposeTo compare the native lateral meniscal kinematics, strain, and tibiofemoral contact pressures to a best-case scenario meniscus transplant with perfectly matched size and position and to determine how sensitive these factors are to subtle changes in shape and position by using a nonanatomic meniscus transplant position.Study designControlled laboratory study.MethodsThe lateral menisci of 8 cadaveric knees were circumferentially implanted with radiopaque spherical markers. They were mounted to a testing apparatus applying muscle and ground-reaction forces. The meniscus was evaluated at 0°, 30°, 90°, and 115° of knee flexion using Roentgen stereophotogrammetric analysis (RSA), with a pressure sensor affixed to the lateral tibial plateau. Measurements were recorded for 3 states: the native lateral meniscus, an anatomic autograft transplant, and a nonanatomic autograft transplant with an anteriorized posterior root position.ResultsAfter transplantation, there was less posterior displacement in both the anatomic and nonanatomic transplant states compared with the native meniscus, but this was not significant. The largest lateral translation in the native state was 2.38 ± 1.58 mm at the anterolateral region from 0° to 90°, which was increased to 3.28 ± 1.39 mm (P = .25) and 3.12 ± 1.18 mm (P = .30) in the anatomic and nonanatomic transplant states, respectively. Internal deformations of the transplant states were more constrained, suggesting less compliance. The native meniscus distributed load over 223 mm2, while both the anatomic (160 mm2) and nonanatomic (102 mm2) states concentrated pressure anteriorly to the tibial plateau centroid.ConclusionThis study is the first to characterize kinematics in the native lateral meniscus compared with a transplanted state utilizing RSA. Results demonstrate increased meniscal constraint and pressure concentrations even after an ideal size and position matched transplantation, which further increased with a nonanatomic posterior root position.Clinical relevanceThe results show that kinematics are similar in both transplanted states when compared with the native meniscus at various flexion angles. Because both transplanted states were more constrained with less deformation compared with the native state, this should allow for relatively safe postoperative range of motion. However, in the transplanted states, peak pressures were distributed over a smaller area and shifted anteriorly. This pattern was exacerbated in the nonanatomic state compared with anatomic. This could have detrimental effects with regard to articular cartilage degeneration, and ultimately result in a failed transplantation.
| S-EPMC5298409 | biostudies-literature
Project description:Though the rabbit is a common animal model in musculoskeletal research, there are very limited data reported on healthy rabbit biomechanics. Our objective was to quantify the normative hindlimb biomechanics (kinematics and kinetics) of six New Zealand White rabbits (three male, three female) during the stance phase of gait. We measured biomechanics by synchronously recording sagittal plane motion and ground contact pressure using a video camera and pressure-sensitive mat, respectively. Both foot angle (i.e., angle between foot and ground) and ankle angle curves were unimodal. The maximum ankle dorsiflexion angle was 66.4 ± 13.4° (mean ± standard deviation across rabbits) and occurred at 38% stance, while the maximum ankle plantarflexion angle was 137.2 ± 4.8° at toe-off (neutral ankle angle = 90 degrees). Minimum and maximum foot angles were 17.2 ± 6.3° at 10% stance and 123.3 ± 3.6° at toe-off, respectively. The maximum peak plantar pressure and plantar contact area were 21.7 ± 4.6% BW/cm2 and 7.4 ± 0.8 cm2 respectively. The maximum net vertical ground reaction force and vertical impulse, averaged across rabbits, were 44.0 ± 10.6% BW and 10.9 ± 3.7% BW∙s, respectively. Stance duration (0.40 ± 0.15 s) was statistically significantly correlated (p < 0.05) with vertical impulse (Spearman's ρ = 0.76), minimum foot angle (ρ = -0.58), plantar contact length (ρ = 0.52), maximum foot angle (ρ = 0.41), and minimum foot angle (ρ = -0.30). Our study confirmed that rabbits exhibit a digitigrade gait pattern during locomotion. Future studies can reference our data to quantify the extent to which clinical interventions affect rabbit biomechanics.
| S-EPMC9208372 | biostudies-literature