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Expert Review of Anti-infective Therapy 2016The HACEK group of bacteria - Haemophilus parainfluenzae, Aggregatibacter spp. (A. actinomycetemcomitans, A. aphrophilus, A. paraphrophilus, and A. segnis),... (Review)
Review
The HACEK group of bacteria - Haemophilus parainfluenzae, Aggregatibacter spp. (A. actinomycetemcomitans, A. aphrophilus, A. paraphrophilus, and A. segnis), Cardiobacterium spp. (C. hominis, C. valvarum), Eikenella corrodens, and Kingella spp. (K. kingae, K. denitrificans) - are fastidious gram-negative bacteria, part of the normal microbiota of oral and upper respiratory tract in humans. Although their pathogenicity is limited, they are responsible for 1-3% of all infective endocarditis. HACEK endocarditis mostly affect patients with underlying heart disease or prosthetic valves, and are characterized by an insidious course, with a mean diagnosis delay of 1 month (Haemophilus spp.) to 3 months (Aggregatibacter and Cardiobacterium spp.). The advent of continuously monitored blood culture systems with enriched media has erased the need for extended incubation for the diagnosis of HACEK endocarditis. Medical treatment relies on third-generation cephalosporin, with a favorable outcome in 80-90% of cases, with or without cardiac surgery.
Topics: Cephalosporins; Endocarditis, Bacterial; Gram-Negative Bacteria; Humans; Risk Factors
PubMed: 26953488
DOI: 10.1586/14787210.2016.1164032 -
Microbiology Spectrum Oct 2022Pneumonia is the leading cause of death in children; the pathogens are often difficult to diagnose. In this study, the performance of metagenomic next-generation...
Pneumonia is the leading cause of death in children; the pathogens are often difficult to diagnose. In this study, the performance of metagenomic next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) samples from 112 children with confirmed pneumonia has been evaluated. mNGS performed a significantly higher positive detection rate (91.07%, 95% confidence interval [CI] 83.80% to 95.40%) and coincidence rate against the final diagnosis (72.32%, 95% CI 62.93% to 80.15%) than that of conventional methods (70.54%, 95% CI 61.06% to 78.58% and 56.25%, 95% CI 46.57% to 65.50%, respectively) ( < 0.01 and < 0.05, respectively). Bacteria, viruses, and their mixed infections were common in children with pneumonia. Streptococcus pneumoniae was the most common bacterial pathogen in children with pneumonia, while Haemophilus parainfluenzae and Haemophilus influenzae seemed more likely to cause nonsevere pneumonia in children. In contrast, human cytomegalovirus (CMV) infection and the simultaneous bacterial infections could cause severe pneumonia, especially in children with underlying diseases. After adjustments of antibiotics based on mNGS and conventional methods, the conditions improved in 109 (97.32%) children. mNGS of BALF samples has shown great advantages in diagnosing the pathogenic etiology of pneumonia in children, especially when considering the limited volumes of BALF and the previous use of empirical antibiotics, contributing to the timely adjustment of antibiotic treatments, which can potentially improve the prognosis and decrease the mortality. Our study indicates high efficiency of mNGS using BALF for the detection of causative pathogens that cause pneumonia in children. mNGS can be a potential diagnostic tool to supplement conventional methods for children's pneumonia.
Topics: Child; Humans; Bronchoalveolar Lavage Fluid; Sensitivity and Specificity; Metagenomics; High-Throughput Nucleotide Sequencing; Pneumonia; Bacteria; Anti-Bacterial Agents
PubMed: 36169415
DOI: 10.1128/spectrum.01488-22 -
Nucleic Acids Research Sep 2023CRISPR-Cas systems act as the adaptive immune systems of bacteria and archaea, targeting and destroying invading foreign mobile genetic elements (MGEs) such as phages....
CRISPR-Cas systems act as the adaptive immune systems of bacteria and archaea, targeting and destroying invading foreign mobile genetic elements (MGEs) such as phages. MGEs have also evolved anti-CRISPR (Acr) proteins to inactivate the CRISPR-Cas systems. Recently, AcrIIC4, identified from Haemophilus parainfluenzae phage, has been reported to inhibit the endonuclease activity of Cas9 from Neisseria meningitidis (NmeCas9), but the inhibition mechanism is not clear. Here, we biochemically and structurally investigated the anti-CRISPR activity of AcrIIC4. AcrIIC4 folds into a helix bundle composed of three helices, which associates with the REC lobe of NmeCas9 and sgRNA. The REC2 domain of NmeCas9 is locked by AcrIIC4, perturbing the conformational dynamics required for the target DNA binding and cleavage. Furthermore, mutation of the key residues in the AcrIIC4-NmeCas9 and AcrIIC4-sgRNA interfaces largely abolishes the inhibitory effects of AcrIIC4. Our study offers new insights into the mechanism of AcrIIC4-mediated suppression of NmeCas9 and provides guidelines for the design of regulatory tools for Cas9-based gene editing applications.
Topics: CRISPR-Cas Systems; CRISPR-Associated Protein 9; RNA, Guide, CRISPR-Cas Systems; Gene Editing; Bacteria; Bacteriophages
PubMed: 37587688
DOI: 10.1093/nar/gkad669 -
Inflammatory Bowel Diseases Mar 2022The first-in-class treatment PF-06480605 targets the tumor necrosis factor-like ligand 1A (TL1A) molecule in humans. Results from the phase 2a TUSCANY trial highlighted...
BACKGROUND
The first-in-class treatment PF-06480605 targets the tumor necrosis factor-like ligand 1A (TL1A) molecule in humans. Results from the phase 2a TUSCANY trial highlighted the safety and efficacy of PF-06480605 in ulcerative colitis. Preclinical and in vitro models have identified a role for TL1A in both innate and adaptive immune responses, but the mechanisms underlying the efficacy of anti-TL1A treatment in inflammatory bowel disease (IBD) are not known.
METHODS
Here, we provide analysis of tissue transcriptomic, peripheral blood proteomic, and fecal metagenomic data from the recently completed phase 2a TUSCANY trial and demonstrate endoscopic improvement post-treatment with PF-06480605 in participants with ulcerative colitis.
RESULTS
Our results revealed robust TL1A target engagement in colonic tissue and a distinct colonic transcriptional response reflecting a reduction in inflammatory T helper 17 cell, macrophage, and fibrosis pathways in patients with endoscopic improvement. Proteomic analysis of peripheral blood revealed a corresponding decrease in inflammatory T-cell cytokines. Finally, microbiome analysis showed significant changes in IBD-associated pathobionts, Streptococcus salivarius, S. parasanguinis, and Haemophilus parainfluenzae post-therapy.
CONCLUSIONS
The ability of PF-06480605 to engage and inhibit colonic TL1A, targeting inflammatory T cell and fibrosis pathways, provides the first-in-human mechanistic data to guide anti-TL1A therapy for the treatment of IBD.
Topics: Colitis, Ulcerative; Fibrosis; Humans; Inflammation; Ligands; Necrosis; Proteomics; Tumor Necrosis Factor Ligand Superfamily Member 15
PubMed: 34427649
DOI: 10.1093/ibd/izab193 -
Gut Pathogens May 2022Over the past decade, the development of next-generation sequencing for human microbiota has led to remarkable discoveries. The characterization of gastric microbiota... (Review)
Review
Over the past decade, the development of next-generation sequencing for human microbiota has led to remarkable discoveries. The characterization of gastric microbiota has enabled the examination of genera associated with several diseases, including gastritis, precancerous lesions, and gastric cancer. Helicobacter pylori (H. pylori) is well known to cause gastric dysbiosis by reducing diversity, because this bacterium is the predominant bacterium. However, as the diseases developed into more severe stages, such as atrophic gastritis, premalignant lesion, and gastric adenocarcinoma, the dominance of H. pylori began to be displaced by other bacteria, including Streptococcus, Prevotella, Achromobacter, Citrobacter, Clostridium, Rhodococcus, Lactobacillus, and Phyllobacterium. Moreover, a massive reduction in H. pylori in cancer sites was observed as compared with noncancer tissue in the same individual. In addition, several cases of H. pylori-negative gastritis were found. Among these individuals, there was an enrichment of Paludibacter, Dialister, Streptococcus, Haemophilus parainfluenzae, and Treponema. These remarkable findings suggest the major role of gastric microbiota in the development of gastroduodenal diseases and led us to the hypothesis that H. pylori might not be the only gastric pathogen. The gastric microbiota point of view of disease development should lead to a more comprehensive consideration of this relationship.
PubMed: 35606878
DOI: 10.1186/s13099-022-00494-0 -
Cureus Jun 2023Infective endocarditis (IE) is a potentially fatal disease that is primarily caused by and . The HACEK group of bacteria ( , , , ) account for only 1-3% of reported IE...
Infective endocarditis (IE) is a potentially fatal disease that is primarily caused by and . The HACEK group of bacteria ( , , , ) account for only 1-3% of reported IE cases. IE has long been known to cause glomerulonephritis. The most common histologic patterns seen are crescentic and diffuse proliferative glomerulonephritis. Notably, membranoproliferative glomerulonephritis (MPGN) is one of the less common patterns seen with IE. We present a rare case of MPGN associated with endocarditis. A 56-year-old male with no significant past medical history presented to a local hospital with complaints of fever, night sweats, dyspnea, diarrhea, and dark urine for about a month. He was found to have a hemoglobin of 4g/dL, requiring multiple transfusions. He also had bilateral pleural effusions and pulmonary edema. In the following days, he had worsening renal function and was transferred to our hospital for further workup. Initial labs showed anemia, thrombocytopenia, and leukocytosis. He had creatinine elevated at 5.28 mg/dL and a low estimated glomerular filtration rate (eGFR) of 12 mL/min/1.73m. Urinalysis showed proteinuria, urine hemoglobin, urine white blood cells (WBCs), and red blood cells (RBCs). Blood cultures revealed . Transesophageal echocardiogram (TEE) showed large vegetations with perforation of the mitral valve leaflet. Serology showed low complement levels. Renal biopsy displayed a membranoproliferative pattern of glomerulonephritis on light microscopy. The hepatitis panel was negative, as was the autoimmune workup. The patient was diagnosed with MPGN associated with endocarditis. His complex clinical course required mitral valve replacement and aortic valve repair. He completed the course of antibiotics, with improvement in renal and cardiac function.
PubMed: 37519594
DOI: 10.7759/cureus.41086 -
Frontiers in Cellular and Infection... 2022There is a bidirectional association between diabetes and periodontitis. However, the effect of diabetes on the periodontitis salivary microbiota has not been...
AIM
There is a bidirectional association between diabetes and periodontitis. However, the effect of diabetes on the periodontitis salivary microbiota has not been elucidated. The aim of this study was to determine the effect of the presence of diabetes on the microbiota among Chinese patients with periodontitis.
MATERIALS AND METHODS
Unstimulated whole saliva samples were collected from the periodontitis with diabetes group (TC), chronic periodontitis group (CP), and periodontally healthy and systemically healthy group (H) by spitting method. Bacterial genomic DNA was PCR-amplified at the V4 variable region of 16S rRNA gene. The library was constructed according to the obtained sequence results, and biological analysis and statistical analysis were carried out. Functional prediction of three groups of microbial communities was performed by the PICRUSt algorithm.
RESULTS
There was no significant difference in bacterial diversity between the TC and CP groups. Compared with the H group, the TC group and CP group presented a higher diversity of salivary flora. , , , , and dominated the H group. , , , , , , , , , , , and were significantly enriched in the TC and CP groups. Among them, and were the most abundant in the TC group. The PICRUSt results showed that many pathways related to cell motility and functional metabolism of the salivary microbial flora changed in the TC group and the CP group.
CONCLUSIONS
Diabetes was not the main factor causing the altered diversity of salivary microbiota in patients with periodontitis; however, the presence of diabetes altered the abundance of some microbiota in saliva.
Topics: China; Chronic Periodontitis; DNA, Bacterial; Diabetes Mellitus; Humans; Microbiota; Porphyromonas gingivalis; RNA, Ribosomal, 16S; Saliva
PubMed: 35979090
DOI: 10.3389/fcimb.2022.933833 -
BioRxiv : the Preprint Server For... Mar 2024( ) is a Gram-negative, pleomorphic rod, highly prevalent and abundant as a commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen....
( ) is a Gram-negative, pleomorphic rod, highly prevalent and abundant as a commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen. occupies multiple niches in the oral cavity, including the tongue dorsum, keratinized gingiva, and the supragingival plaque biofilm. As a member of the HACEK group, is also known to cause infective endocarditis. Additionally, case reports have identified as the causative agent of meningitis, septic arthritis, chronic osteomyelitis, septicemia, and a variety of other infectious diseases. Little is known about how interacts with its neighbors in the healthy biofilm nor about its mechanisms of pathogenesis as an extraoral opportunistic pathogen. To address these unknowns, we identified the essential genomes of two strains and the conditionally essential genes for their growth in biofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturated transposon library in two strains, the ATCC33392 type-strain ( 392) and a commensal oral isolate EL1 ( EL1), we show that the essential genome of 392 and EL1 is composed of 395 and 384 genes, respectively. The core essential genome, consisting of 341 essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains of . Additionally, RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential for 392 anaerobic biofilm survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology of in differing oxygen conditions, similar to its oral habitat. Further, the creation of this library presents a valuable tool for further investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.
PubMed: 38585970
DOI: 10.1101/2024.03.31.587483 -
Archives of Disease in Childhood Jul 1994
Topics: Child, Preschool; Culture Media; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Urinary Tract Infections
PubMed: 8067803
DOI: 10.1136/adc.71.1.95