SEARCH · PubMed Health

Results for “Type IV Secretion Systems”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

15 recordsLinked to original sources

PubMed2026

Unveiling a missing component of the atypical type IV secretion system required for natural transformation of Helicobacter pylori.

Exchange of genetic information by natural transformation shapes bacterial evolution. In Helicobacter pylori it is thought to drive its unusually high recombination rate, which has a crucial role in the evolution of virulence and the propagation of antibiotics resistance genes. While in most cases uptake of the incoming DNA into the periplasm is mediated by type IV pili, in H. pylori this initial step of natural transformation requires ComB, a unique competence-specific type IV secretion system (T4SS). The mechanisms by which ComB mediates DNA uptake are still poorly understood, since T4SS are usually involved in an opposite process of DNA export. Here, we identify a gene (hp1421) that is absolutely required for uptake of the transforming DNA into the periplasm, although distant from the comB operons. We show that hp1421 codes for a hexameric ATPase from the VirB11 family. HP1421 is present in the cytoplasm and interacts with ComB4, another ATPase of the T4SS inner membrane subcomplex. The structural modelling and functional analysis of HP1421 and its interaction with ComB4 indicate that HP1421 is a missing component of the ComB inner-membrane subcomplex that we propose to name ComB11. Phylogenetic analyses show that comB11 is a H. pylori core gene and suggest that the competence-dedicated ComB T4SS was a recent acquisition within Helicobacteraceae. Hence, co-option of the T4SS for DNA transformation requires nearly all the proteins that were previously essential for DNA conjugation.

Helicobacter pylori↗

PubMed2026

Unveiling a missing component of the atypical type IV secretion system required for natural transformation of Helicobacter pylori.

Journal Article↗

PubMed2026

Genomic analysis of Neisseria gonorrhoeae strains from disseminated, urogenital, and rectal infections reveals differences in genes for iron acquisition and type IV secretion.

Neisseria gonorrhoeae, an obligate human pathogen, causes the sexually transmitted infection gonorrhea. Delayed treatment or immunodeficiencies can result in a higher risk of disseminated gonococcal infection (DGI), where the infection spreads to normally sterile anatomic sites, including the bloodstream. The gonococcus produces TonB-dependent transporters (TdTs) to sequester metals from host nutritional immunity proteins. These transporters are critical for survival and are important virulence factors. We characterized genes encoding iron-regulated TdTs in the genomes of strains from disseminated (n = 47), urogenital (n = 86), and rectal (n = 12) infections. We found that gonococcal strains isolated from DGI infections were more likely to express a functional hemoglobin-iron utilization operon (hpuAB wild type and phase on [32%, n = 15/47]), to harbor nonsense mutations in tdfF (57%, n = 27/47), and were predicted to express low levels of fetA (43%, n = 20/47) when compared to strains from urogenital or rectal infections. In contrast, gonococcal strains from localized urogenital infections were associated with a higher frequency of functional tdfF genes (66%, n = 57/86) and high fetA expression (30%, n = 26/86). Additionally, strains from rectal infections were more frequently found to have high fetA expression (33%, n = 4/12) and a functional tdfF (75%, n = 9/12). Furthermore, we identified associations between the presence and absence of tdfF and the gonococcal genetic island, which encodes a type IV secretion system. These findings inform our evolving understanding of the molecular mechanisms underlying disseminated gonococcal infections.IMPORTANCEGonorrhea is an emerging, global health threat, with over 100 million new cases each year. Delayed treatment, immunosuppressive medications, and immunodeficiencies can contribute to the spread of infection to the blood, presenting as a serious disseminated manifestation. With rising antimicrobial resistance and no licensed preventative vaccine, untreatable gonorrhea is a possibility in the near future. TonB-dependent transporters are highly conserved and vital for metal acquisition and survival, making them promising targets for therapeutic or preventative strategies. Associated surface-exposed lipoproteins display greater sequence variation but contribute to metal acquisition. We analyzed the genes encoding TonB-dependent transporters and associated lipoproteins from strains associated with distinct disease manifestations. We conclude that gonococci isolated from disseminated, urogenital, and rectal sites demonstrate different phase and allelic variations in genes encoding iron transport systems and the gonococcal genetic island.

Humans↗

PubMed2025

Characterization of gut microbiota signatures in Indian preterm infants with necrotizing enterocolitis: a shotgun metagenomic approach.

INTRODUCTION: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease that primarily affects preterm infants. Predisposing risk factors for NEC include prematurity, formula feeding, anemia, and sepsis. To date, no studies have investigated the gut microbiota of preterm infants with NEC in India. METHOD: In the current study, shotgun metagenomic sequencing was performed on fecal samples from premature infants with NEC and healthy preterm infants (n = 24). Sequencing was conducted using the NovaSeq X Plus platform, generating 2 × 150 bp paired-end reads. The infants were matched based on gestational age and postnatal age. RESULT: The median time to NEC diagnosis was 9 days (range: 1-30 days). Taxonomic analysis revealed a high prevalence of Enterobacteriaceae at the family level, with the genera Klebsiella and Escherichia particularly prominent in neonates with NEC. No statistically significant differences in alpha or beta diversity were observed between stool samples from infants with and without NEC. Linear regression analysis demonstrated that Enterobacteriaceae were significantly more abundant in stool samples from infants with NEC than without NEC (q < 0.05). Differential abundance analysis using Linear Discriminant Analysis Effect Size (LEfSe) identified Klebsiella pneumoniae and Escherichia coli as enriched in the gut microbiota of preterm infants with NEC. Functional analysis revealed an increase in genes associated with lipopolysaccharide (LPS) O-antigen, the type IV secretion system (T4SS), the L-rhamnose pathway, quorum sensing, and iron transporters, including ABC transporters, in stool samples from infants with NEC. CONCLUSION: The high prevalence of Enterobacteriaceae and enrichment of LPS O-antigen and T4SS genes may be associated with NEC in Indian preterm infants.

Humans↗

PubMed2026

Occurrence of blaOXA-72 in a clinical isolate of carbapenem-resistant Acinetobacter pittii ST206 in Japan.

The development of carbapenem resistance in Acinetobacter spp., which are recognized as significant opportunistic pathogens, is of critical importance as it poses challenges to therapy and the control of healthcare-associated infections in clinical settings. This study investigated the genetic characteristics of a carbapenem-resistant A. pittii clinical isolate from a university hospital using whole-genome sequencing. The A. pittii strain SU8507, which was detected in the abdominal drainage fluid of a patient, exhibited resistance to imipenem (MIC: 128 μg/mL) and meropenem (MIC: 64 μg/mL) and produced positive results by the CIMTris method. A. pittii SU8507, belonging to ST206, harbored the blaOXA-72 and new variants of intrinsic blaOXA-213-like gene blaOXA-1222, which lacks an upstream insertion sequence element, and blaADC-1-like gene blaADC-343. The blaOXA-72 gene, flanked by XerC/XerD-like recombination sites, was located on a plasmid pSU8507, sized at 10,913 bp, carrying 13 predicted protein-coding genes. Complete pSU8507 containing mobA, repB, and the yoeB-yefM toxin-antitoxin genes, showed 98.9% nucleotide sequence identity and 75% coverage with plasmid pA2702 of the A. baylyi strain A2702, but a low BLAST MAX score. SU8507 harbored virulence genes involved in biofilm formation, types II and VI secretion systems, type IV pilus system, and serum resistance. This study describes the first isolation of an OXA-72-producing, carbapenem-resistant A. pittii clinical isolate in Japan. Given that the isolation rate of carbapenem-resistant Acinetobacter spp. Remains low in Japan, it is crucial to expand the scope of rapid, accurate carbapenemase detection to include not only A. baumannii, but also non-baumannii Acinetobacter spp.

Humans↗

PubMed2025

Type IV Pili-Associated Secretion of a Biofilm Matrix Protein From Clostridium perfringens That Forms Intermolecular Isopeptide Bonds.

Clostridium perfringens is a gram-positive, anaerobic, spore-forming bacterial pathogen of humans and animals. C. perfringens also produces type IV pili (T4P) and has two complete sets of T4P-associated genes, one of which has been shown to produce surface pili needed for cell adherence. One hypothesis about the second set of T4P genes is that they comprise a type II secretion system (TTSS) like those found in gram-negative bacteria, but for gram-positive bacteria, the TTSS would aid transit across the thick peptidoglycan (PG) layer. The secretome of mutants lacking type IV pilins was examined, and a single protein, BsaC (CPE0517), was identified as being dependent on pilin PilA3 for secretion. The bsaC gene is in an operon with genes encoding a SipW signal peptidase and two putative biofilm matrix proteins, BsaA and BsaB, both of which have remote homology to Bacillus subtilis biofilm protein TasA. Since BsaA forms long oligomers that are secreted, we analyzed BsaA monomer interactions with de novo modeling. These models projected that the monomers formed isopeptide bonds as part of a donor strand exchange process. Mutations in residues predicted to form the isopeptide bonds led to the loss of oligomerization, supporting an exchange and lock mechanism, and isopeptide bonds were detected by mass spectrometry methods. Phylogenetic analysis showed the BsaA family of proteins is widespread among bacteria and archaea, but only a subset is predicted to form isopeptide bonds.

Fimbriae, Bacterial↗

PubMed1979

Collagen synthesis by bovine aortic endothelial cells in culture.

Endothelial cells isolated from bovine aorta synthesize and secrete type III procollagen in culture. The procollagen, which represents the major collagenous protein in culture medium, was specifically precipitated by antibodies to bovine type III procollagen and was purified by diethyl-aminoethylcellulose chromatography. Unequivocal identification of the pepsin-treated collagen was made by direct comparison with type III collagen isolated by pepsin digestion of bovine skin, utilizing peptide cleavage patterns generated by vertebrate collagenase, CNBr, and mast cell protease. The type III collagen was hydroxylated to a high degree, having a hydroxyproline/proline ratio of 1.5:1.0. Pulse-chase studies indicated that the procollagen was not processed to procollagen intermediates or to collagen. Pepsin treatment of cell layers, followed by salt fractionation at acidic and neutral pH, produced several components which were sensitive to bacterial collagenase and which comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with alpha A, alpha B, and type IV collagen chains purified from human placenta by similar techniques. Bovine aortic endothelial cells also secreted fibronectin and a bacterial collagenase-insensitive glycoprotein which, after reduction, had a molecular weight of 135,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (using procollagen molecular weight standards) and which was not precipitable by antibodies to cold-insoluble globulin or to alpha 2-macroglobulin. Collagen biosynthesis by these cells provides an interesting model system for studying the polarity of protein secretion and the attachment of cells to an extracellular matrix. The presence of type III collagen in the subendothelium and the specific interaction of this protein with fibronectin and platelets suggest the involvement of this collagen in thrombus formation following endothelial cell injury.

Animals↗

PubMed1979

Intrapulmonary clotting and fibrinolysis during abdominal aortic aneurysm surgery.

Intravascular clotting and fibrinolysis (C and F) are events which often accompany major surgical trauma. Their role in inducing cardiopulmonary failure is debated and prompted this study of 13 patients undergoing elective AAA. Following intubation, anesthesia and pressure breathing fibrinolytic activity (FA) in arterial blood exceeded that in mixed venous blood (p < 0.001) indicating pulmonary secretion of proteolytic activity. Fibrinogen, plasminogen and fibrin degradation products (FDPs) were normal. During surgery, fibrinogen and plasminogen fell (p < 0.001) while nonplasmin mediated FA and FDPs rose (p < .001). Despite heparinization (5000 U IV) aortic clamping (avg 56 min) led to evidence of C and F within the lungs. Arterial fibrinogen was 33.2 mg/ml lower than mixed venous blood (p < 0.01) and plasminogen was 0.47 Sherry units lower (p < 0.001). Soluble fibrin monomer appeared in arterial blood (p < 0.01). At the same time nonplasmin mediated FA was consumed within the lungs (p < 0.01) and FDPs were produced (44.6 microg/ml higher in arterial blood, p < 0.001). Similar changes were noted after aortic declamping. The transient 5.3 ml/cm H(2)0 fall in dynamic compliance was unrelated to C and F. Pulmonary vascular resistance and arterial pressure were unchanged. During wound closure intrapulmonary C and F ceased. Postoperatively (6 h), the physiologic shunt of 15.1% was similar to tbe preoperative value of 13.3%. All C and F factors returned to normal except FDPs which remained elevated. An average of 0.2 U blood was given prior to aortic clamping and 3.1 U during clamping. Neither the volume nor the type of blood (7 patients received washed RBCs) influenced pulmonary C and F. The results show that pressure breathing will alter pulmonary metabolism from clearance to secretion of fibrinolytic activity. Surgery leads to systemic C and F while intrapulmonary C and F is triggered by aortic clamping despite IV heparin. Delayed functional consequences of C and F are possible. Immediate postoperative effects are not apparent.

Aorta, Abdominal↗

PubMed2025

Comparative genomics of carbapenem-resistant Acinetobacter baumannii isolated from pediatric patients in a tertiary care hospital.

Acinetobacter baumannii is a short gram-negative bacillus, notable for its intrinsic multidrug resistance and genomic plasticity, which facilitates the acquisition of additional resistance genes via mobile genetic elements. Due to its increasing carbapenem resistance, the World Health Organization has classified it as a critical priority pathogen. This study performed a comparative genomic analysis of 20 carbapenem-resistant A. baumannii clinical strains isolated from the Hospital Infantil de México Federico Gómez (CRAB-HIMFG), alongside 11 genomes from other Mexican strains. The pangenome was determined to be open, and core genome single-nucleotide polymorphism-based analysis grouped the CRAB-HIMFG strains within CC758/IC5 and CC92/IC2. A novel sequence type (ST) in the MLST-Pasteur scheme was identified, related to STPas156, and in the MLST-Oxford scheme, associated with STOxf758 and STOxf1054. Virulence and resistance genes comprised 0.61% to 2.23% of the pangenome. Oxacillinase genes and efflux pumps primarily mediated carbapenem resistance, while virulence genes included those encoding biofilm and type IV pili. Capsule typing revealed a correlation with established international clones, IC2 and IC5. Plasmids exhibited high diversity, harboring maintenance modules and toxin-antitoxin systems, with the dissemination of resistance genes linked to insertion sequences. Biofilm formation and twitching motility were not always expressed, as they depend on additional environmental factors. Our study shows that comparative genomics is an essential tool to analyze clinically and epidemiologically significant genomes, providing critical insights into gene distribution, genomic architecture, and horizontal gene transfer mechanisms in microbial populations.IMPORTANCEIn recent years, a reported increase in the mortality rate associated with infections caused by A. baumannii, along with a rise in carbapenem resistance, poses a serious clinical challenge. The WHO considered this microorganism critical for research into alternative therapies and epidemiological surveillance. Despite advances in bioinformatics, genomic studies have yet to fully elucidate the structural rearrangements and secretion systems of A. baumannii. This knowledge gap hinders our understanding of its remarkable genomic plasticity and its ability to acquire and spread resistance and virulence genes through horizontal gene transfer.

Acinetobacter baumannii↗

PubMed2025

An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE.

Bacteria deploy a diverse arsenal of toxic effectors to antagonize competitors, profoundly influencing the composition of microbial communities. Previous studies have identified an interbacterial toxin predicted to exhibit proteolytic activity that is broadly distributed among gram-negative bacteria. However, the precise mechanism of intoxication remains unresolved. Here, we demonstrate that one such protease toxin from Escherichia coli, Cpe1, disrupts DNA replication and chromosome segregation by cleaving conserved sequences within the ATPase domain of type II DNA topoisomerases GyrB and ParE. This cleavage effectively inhibits topoisomerase-mediated relaxation of supercoiled DNA, resulting in impaired bacterial growth. Cpe1 belongs to the papain-like cysteine protease family and is associated with toxin delivery pathways, including the type VI secretion system and contact-dependent growth inhibition. The structure of Cpe1 in complex with its immunity protein reveals a neutralization mechanism involving competitive substrate binding rather than active site occlusion, distinguishing it from previously characterized effector-immunity pairs. Our findings unveil a unique mode of interbacterial intoxication and provide insights into how bacteria protect themselves from self-poisoning by protease toxins.

Escherichia coli↗

PubMed1978

Intracellular transport and packaging of prolactin: a quantitative electron microscope autoradiographic study of mammotrophs dissociated from rat pituitaries.

Dispersed pituitary cells prepared from estrogen-treated female rats were subjected to pulse labeling with [3H]leucine (5 min) followed by a chase incubation (up to 3 h) in order to study intracellular transport of PRL in mammotrophs. Sites of synthesis, rates of transport, and sites of packaging and storage of PRL were determined by quantitative electron microscopic autoradiography. Results of grain counts show that label is initially (end of pulse) distributed randomly over the rough endoplasmic reticulum (ER), but rapidly (5--15 min of chase) moves to the stacked Golgi cisternae where concentration into secretion granules takes place. The label moves successively from small (Type I) immature granules (15--55 min of chase) to large (Types II and III) polymorphic granules (55--115 min) in the Golgi region, to rounded or ovoid mature (Type IV) granules (55--185 min) usually found in the peripheral cytoplasm, indicating that these types of granules represent successive stages in granule concentration and assembly. Analysis of the relative grain density (percentage of total grains/percentage of total area) confirmed that there was progressive concentration (up to 20--150 times) along the transport route with the concentration lowest in the ER, higher in the Golgi, and highest in immature and mature secretion granules. These data indicate that synthesis of PRL occurs randomly in the ER, transport to the Golgi occurs rapidly (within 5--10 min), and is completed rapidly (90% within 15--20 min), and concentration into granules and aggregation of small granules into larger forms also occurs rapidly (by 15--20 min), but goes on over a prolonged period of time (up to 3 h). Use of dispersed cells has allowed a more precise determination of the location and kinetics of steps in the intracellular processing of PRL than has been possible previously using other systems.

Animals↗

PubMed1978

The role of macrophage activation in chronic inflammation.

The macrophage is the characteristic cell type in chronic inflammatory reactions, in the rheumatoid synovium, as in other sites. When macrophages are activated, considerable synthesis of enzymes and other proteins occurs. Macrophages can be activated by (i) products of activated lymphocytes, (ii) immune complexes and (iii) the complement cleavage product C3b. Among the many consequences of macrophage activation are (i) secretion of hydrolytic enzymes, (ii) cleavage of C3 into C3a, which is cytolytic, and C3b, (iii) production of tissue thromboplastin, a powerful procoagulant, and (iv) formation of polyamine oxidase, which in the presence of appropriate substrates generates factors that lyse or limit the proliferation of tumour cells, lymphocytes and micro-organisms. The relevance of these observations to the pathogenesis of chronic inflammatory reactions is discussed.

Animals↗

PubMed1979

Characterization of a type IV procollagen synthesized by human amniotic fluid cells in culture.

Fetal epithelioid cells, isolated from human amniotic fluid, synthesize and secrete a type IV-like procollagen characterized by a unique pattern of cyanogen bromide (CNBr)-produced peptides. The procollagen is disulfide-bonded and, after reduction, migrates on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a doublet between collagen beta components and pro-alpha 1(I) chains. No conversion of the procollagen to collagen or to procollagen intermediates is observed in cell culture. The procollagen was purified by salt fractionation and ion exchange chromatography; its amino acid composition resembles that of collagenous proteins extracted from basement membranes, with a high 3- and 4-hydroxyproline and hydroxylysine content and low levels of alanine and arginine. The major products obtained after limited proteolytic digestion of the protein retain interchain disulfide bonds and, after reduction, migrate on sodium dodecyl sulfate-polyacrylamide gel electrophoresis near intact pro-alpha 1(I) chains. The procollagen is secreted efficiently by amniotic fluid cells despite almost complete inhibition of peptidyl hydroxylation but, unlike type I procollagen, the secreted underhydroxylated chains lack interchain disulfide bonds. Since these cells also secrete fibronectin and elaborate an extensive extracellular matrix, the system should prove useful in the study of cell-matrix interactions.

Amino Acids↗

PubMed1976

Purification and characterization of a new family of polypeptide neurotoxins from the heteronemertine Cerebratulus lacteus (Leidy).

Mucus secreted from the integument of the marine heteronemertine Cerebratulus lacteus (Leidy) contains two major types of polypeptide neurotoxin: the A toxins (11,000 daltons) which are lethal to a variety of animal species including mammals, and the B toxins (6,000 daltons) which appear to be selectively toxic for crustaceans. Both types of toxin were readily obtained from live worms by stimulation and collection of mucus with 1% acetic acid followed by batch adsorption of the basic polypeptide fraction upon CM-cellulose. Separate A and B toxin fractions were obtained by gel chromatography. Four toxins were purified from the B toxin fraction by CM-cellulose gradient elution chromatography. Each consists of a single polypeptide chain with NH2-terminal alanine and three (B-I) or four (B-II, B-III, B-IV) intrachain disulfide bonds. All four B toxins contain large proportions of lysine and exhibit identical gel electrophoretic mobilities at neutral pH. The B toxins lack cysteine and reducing sugar moieties. Toxin B-I differs considerably from the others in its amino acid composition and its shorter chain length (49 instead of 53 or 54 residues). The other three toxins have similar compositions, but lack proline, methionine, and phenylalanine. All four polypeptides show crustacean-selective toxicities which vary over a 30-fold range; B-II possesses the highest toxicity. As a working hypothesis it is suggested that the Cerebratulus B toxins are isotoxins which act via a common receptor present in crustacean axon membranes.

Amino Acids↗

PubMed1979

Determinants in microbial colonization of the murine gastrointestinal tract: pH, temperature, and energy-yielding metabolism of Torulopsis pintolopesii.

Torulopsis pintolopesii is an indigenous yeast that colonizes the secreting epithelia in the stomachs of mice and rats. A wild-type strain of this microbe was isolated and identified. To attempt to learn characteristics of the yeast that are advantageous to it in colonizing its natural habitat in vivo, we examined some aspects of its nutrition and energy-yielding metabolism and some environmental conditions that influence its growth in vitro. The yeast appeared to be limited in the compounds it can utilize as carbon and nitrogen sources. It grew best at 37 degrees C and did not grow at 23 or 43 degrees C. It grew optimally at neutral pH but could grow aerobically at pH values as low as 2.0 and anaerobically at pH values as low as 3.4. As assessed by measurements of growth rates and yield coefficients, it grew better aerobically than anaerobically. When grown aerobically, it had a cyanide-sensitive system for taking up O(2) and tested positively for cytochrome c oxidase activity. A petite mutant strain isolated from the wild-type strain had a growth rate and yield coefficient when incubated aerobically that were essentially the same as those of the wild-type parent grown anaerobically. Likewise similar to the wild-type parent grown anaerobically, the petite strain, though incubated aerobically, did not take up O(2). Yeast-free mice associated with either the wild-type or the petite mutant strain were colonized at essentially the same rates and to similar final population levels by both strains. The yeast's capacity to respire may be of little advantage to it in its natural environment. By contrast, its abilities to grow best at 37 degrees C and to grow at low pH values are undoubtedly advantageous characteristics in this respect. The limitations in its carbon and nitrogen nutrition are difficult to evaluate as ecological factors in its colonization of the natural habitat.

Animals↗