Authors: May A Beydoun, Hind A Beydoun, Sharmin Hossain...

Microbial agents including periodontal pathogens have recently appeared as important actors in Alzheimer's disease (AD) pathology. We examined associations of clinical periodontal and bacterial parameters with incident all-cause and AD dementia as well as AD mortality among US middle-aged and older adults. Clinical [Attachment Loss (AL); probing pocket depth (PPD)] and bacterial [pathogen immunoglobulin G (IgG)] periodontal markers were investigated in relation to AD and all-cause dementia incidence and to AD mortality, using data from the third National Health and Nutrition Examination Surveys (NHANES III, 1988-1994) linked longitudinally with National Death Index and Medicare data through January 1, 2014, with up to 26 years of follow-up. Sex- and age-specific multivariable-adjusted Cox proportional hazards models were conducted. Among those ≥65 years, AD incidence and mortality were consistently associated with PPD, two factors and one cluster comprised of IgG titers against Porphyromonas gingivalis (P. gingivalis), Prevotella melaninogenica (P. melaninogenica) and Campylobacter rectus (C. rectus) among others. Specifically, AD incidence was linked to a composite of C. rectus and P. gingivalis titers (per SD, aHR = 1.22; 95% CI, 1.04-1.43, p = 0.012), while AD mortality risk was increased with another composite (per SD, aHR = 1.46; 95% CI, 1.09-1.96, p = 0.017) loading highly on IgG for P. gingivalis, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, C. rectus, Streptococcus intermedius, Capnocylophaga Ochracea, and P. melaninogenica. This study provides evidence for an association between periodontal pathogens and AD, which was stronger for older adults. Effectiveness of periodontal pathogen treatment on reducing sequelae of neurodegeneration should be tested in randomized controlled trials.

Topics: Aged; Alzheimer Disease; Campylobacter rectus; Dementia; Female; Health Surveys; Humans; Incidence; Male; Middle Aged; Periodontitis; Porphyromonas gingivalis; Prevotella melaninogenica; United States

PubMed: 32280099
DOI: 10.3233/JAD-200064

Authors: Cody Thomas, Harald Nothaft, Ruchi Yadav...

Ecotin, first described in Escherichia coli, is a potent inhibitor of a broad range of serine proteases including those typically released by the innate immune system such as neutrophil elastase (NE). Here we describe the identification of ecotin orthologs in various Campylobacter species, including Campylobacter rectus and Campylobacter showae residing in the oral cavity and implicated in the development and progression of periodontal disease in humans. To investigate the function of these ecotins in vitro, the orthologs from C. rectus and C. showae were recombinantly expressed and purified from E. coli. Using CmeA degradation/protection assays, fluorescence resonance energy transfer and NE activity assays, we found that ecotins from C. rectus and C. showae inhibit NE, factor Xa and trypsin, but not the Campylobacter jejuni serine protease HtrA or its ortholog in E. coli, DegP. To further evaluate ecotin function in vivo, an E. coli ecotin-deficient mutant was complemented with the C. rectus and C. showae homologs. Using a neutrophil killing assay, we demonstrate that the low survival rate of the E. coli ecotin-deficient mutant can be rescued upon expression of ecotins from C. rectus and C. showae. In addition, the C. rectus and C. showae ecotins partially compensate for loss of N-glycosylation and increased protease susceptibility in the related pathogen, Campylobacter jejuni, thus implicating a similar role for these proteins in the native host to cope with the protease-rich environment of the oral cavity.

Topics: Animals; Campylobacter; Campylobacter rectus; Cells, Cultured; Chickens; Escherichia coli Proteins; Humans; Neutrophils; Pancreatic Elastase; Periplasmic Proteins; Sequence Homology; Serine Proteinase Inhibitors; Trypsin Inhibitors

PubMed: 33378351
DOI: 10.1371/journal.pone.0244031

Authors: Amos Aranowicz, Stephanie L van den Brandt, Ksenija Slankamenac...

We present a rare case of destructive osteomyelitis of the sternum caused by and A previously healthy female patient in her 40s presented to the emergency department due to a spontaneous rupture of an abscess located to the chest wall. Imaging confirmed abscess formation with osteomyelitis of the sternum. Emergent surgical debridement was performed, blood and bone cultures were taken and the patient received antibiotic treatment. Cultures of the bone and deep tissue revealed infection with and , both being members of the oral flora and associated with chronic periodontitis. Receiving targeted antibiotic treatment, our patient made a quick recovery. After treatment of the osteomyelitis, our patient was referred to the dentist where chronic periodontitis could be confirmed. Invasive infections with and are rare. Investigation of a dental origin is crucial to prevent recurrent infections.

Topics: Abscess; Anti-Bacterial Agents; Campylobacter rectus; Chronic Periodontitis; Female; Firmicutes; Humans; Osteomyelitis; Peptostreptococcus

PubMed: 36137645
DOI: 10.1136/bcr-2022-250886

Authors: Ming Chen, Xiangquan Song, Miao Shi...

Pneumonia caused by is very rare. Herein, we describe the treatment course and experiences of a patient with pneumonia caused by . A 64-year-old woman with intermittent hemoptysis and part lung necrosis indicated by radiography was admitted to our hospital on March 15, 2021. After admission, a CT (Computer tomography)-guided percutaneous lung biopsy was identified as positive by bacterial culture and metagenomic sequencing. The hemoptysis resolved, and the lesions in the right lower lung were gradually absorbed after treatment with anti- drugs. In cases of pneumonia which unresolved by initial therapy and associated with more severe oral hygiene problems, the possibility of infection with oral pathogens (eg, ) should be considered. This case suggests that bacterial culture and metagenomic sequencing of the diseased tissue, particularly anaerobic culture, helps to clarify the etiological diagnosis.

PubMed: 37809773
DOI: 10.1016/j.heliyon.2023.e20014

Authors: Casey Hughes Lago, Dana Blackburn, Meghan Kinder Pavlicek...

is a gram-negative, anaerobic bacterium strongly associated with periodontitis. It also causes various extraoral infections and is linked to adverse pregnancy outcomes in humans and murine models. and related oral have been termed "emerging species" because infections by these organisms are likely underreported. Previously, no comparative methods have been used to analyze more than single strains and until recently, very few genomes have been publicly available. More sequenced genomes and comparative analyses are needed to study the genomic features and pathogenicity of this species. We sequenced eight new strains and used comparative methods to identify regions of interest. An emphasis was put on the type III flagellar secretion system (T3SS), type IV secretion system (T4SS), and type VI secretion system (T6SS) because these protein complexes are important for pathogenesis in other species. RAST, BV-BRC, and other bioinformatics tools were used to assemble, annotate, and compare these regions in the genomes. The pan-genome of consists of 2670 genes with core and accessory genomes of 1429 and 1241 genes, respectively. All isolates analyzed in this study have T3SS and T6SS hallmark proteins, while five of the isolates are missing a T4SS system. Twenty-one prophage clusters were identified across the panel of isolates, including four that appear intact. Overall, significant genomic islands were found, suggesting regions in the genomes that underwent horizontal gene transfer. Additionally, the high frequency of CRISPR arrays and other repetitive elements has led to genome rearrangements across the strains, including in areas adjacent to secretion system gene clusters. This study describes the substantial diversity present among isolates and highlights tools/assays that have been developed to permit functional genomic studies. Additionally, we have expanded the studies on T4SS since we have two new genomes to report. We also demonstrate that unlike , does not demonstrate evidence of intact T6SS except for the strain CAM. The only strain of sequenced has neither T4SS or T6SS.

PubMed: 39211246
DOI: 10.1101/2024.07.26.605372

Authors: Yuki Munekata, Saki Yamamoto, Shun Kato...

We report a fatal subdural empyema caused by in a 66-year-old female who developed acute onset of confusion, dysarthria, and paresis in her left extremities. A CT scan showed hypodensity in a crescentic formation with a mild mid-line shift. She had a bruise on her forehead caused by a fall several days before admission, which initially raised subdural hematoma (SDH) diagnosis, and a burr hole procedure was planned. However, her condition deteriorated on the admission night, and she died before dawn. An autopsy revealed that she had subdural empyema (SDE) caused by and . Both microorganisms are oral microorganisms that rarely cause extra-oral infection. In our case, head trauma caused a skull bone fracture, and sinus infection might have expanded to the subdural space causing SDE. CT/MRI findings were not typical for either SDH or SDE. Early recognition of subdural empyema and prompt initiation of treatment with antibiotics and surgical drainage is essential for cases of SDE. We present our case and a review of four reported cases.

PubMed: 37415644
DOI: 10.4322/acr.2023.433

Comparative Study

Authors: H Nitta, S C Holt, J L Ebersole...

Campylobacter rectus is a putative periodontopathogen which expresses a proteinaceous surface layer (S-layer) external to the outer membrane. S-layers are considered to play a protective role for the microorganism in hostile environments. The S-layer proteins from six different C. rectus strains (five human isolates and a nonhuman primate [NHP] isolate) were isolated, purified, and characterized. The S-layer proteins of these strains varied in molecular mass (ca. 150 to 166 kDa) as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. They all reacted with monospecific rabbit antiserum to the purified S-layer of C. rectus 314, but a quantitative enzyme-linked immunosorbent assay demonstrated a strong antigenic relationship among the five human strains, while the NHP strain, 6250, showed weaker reactivity. Amino acid composition analysis showed that the S-layers of four C. rectus strains contained large proportions of acidic amino acids (13 to 27%) and that >34% of the amino acid residues were hydrophobic. Amino acid sequence analysis of six S-layer proteins revealed that the first 15 amino-terminal amino acids were identical and showed seven residues of identity with the amino-terminal sequence of the Campylobacter fetus S-layer protein SapA1. CNBr peptide profiles of the S-layer proteins from C. rectus 314, ATCC 33238, and 6250 confirmed that the S-layer proteins from the human strains were similar to each other and somewhat different from that of the NHP isolate (strain 6250). However, the S-layer proteins from the two human isolates do show some structural heterogeneity. For example, there was a 17-kDa fragment unique to the C. rectus 314 S-layer. The amino-terminal sequence of this peptide had homology with the C. rectus 51-kDa porin and was composed of nearly 50% hydrophobic residues. Thus, the S-layer protein from C. rectus has structural heterogeneity among different human strains and immunoheterogeneity with the NHP strain.

Topics: Amino Acid Sequence; Amino Acids; Animals; Bacterial Outer Membrane Proteins; Bacterial Proteins; Campylobacter; Cyanogen Bromide; Humans; Membrane Glycoproteins; Molecular Sequence Data; Peptide Fragments; Species Specificity

PubMed: 9009300
DOI: 10.1128/iai.65.2.478-483.1997

Comparative Study Review

Authors: C Roy D Lancaster, Jörg Simon

The epsilon-proteobacteria form a subdivision of the Proteobacteria including the genera Wolinella, Campylobacter, Helicobacter, Sulfurospirillum, Arcobacter and Dehalospirillum. The majority of these bacteria are oxidase-positive microaerophiles indicating an electron transport chain with molecular oxygen as terminal electron acceptor. However, numerous members of the epsilon-proteobacteria also grow in the absence of oxygen. The common presence of menaquinone and fumarate reduction activity suggests anaerobic fumarate respiration which was demonstrated for the rumen bacterium Wolinella succinogenes as well as for Sulfurospirillum deleyianum, Campylobacter fetus, Campylobacter rectus and Dehalospirillum multivorans. To date, complete genome sequences of Helicobacter pylori and Campylobacter jejuni are available. These bacteria and W. succinogenes contain the genes frdC, A and B encoding highly similar heterotrimeric enzyme complexes belonging to the family of succinate:quinone oxidoreductases. The crystal structure of the W. succinogenes quinol:fumarate reductase complex (FrdCAB) was solved recently, thus providing a model of succinate:quinone oxidoreductases from epsilon-proteobacteria. Succinate:quinone oxidoreductases are being discussed as possible therapeutic targets in the treatment of several pathogenic epsilon-proteobacteria.

Topics: Citric Acid Cycle; Electron Transport; Electron Transport Complex II; Energy Metabolism; Fumarates; Models, Chemical; Models, Molecular; Multienzyme Complexes; Operon; Oxidation-Reduction; Oxidoreductases; Proteobacteria; Succinate Dehydrogenase; Succinic Acid; Wolinella

PubMed: 11803019
DOI: 10.1016/s0005-2728(01)00230-4

Authors: Ryoichi Matsumoto, Daisuke Himeji, Ritsuya Shiiba...

Campylobacter rectus is a campylobacterium considered to be a primary periodontal pathogen. Thus, C. rectus has rarely been isolated from extraoral specimens, especially in the thoracic region. We herein report a case of thoracic empyema in which Campylobacter infection was suspected after Gram staining of the pleural effusion, and C. rectus was isolated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fusobacterium nucleatum was also detected. Molecular identification was performed using polymerase chain reaction amplification and a sequencing analysis of the 16S rRNA gene. Estimation of the causative bacteria using Gram staining led to the proper culture and identification of the causative bacteria.

Topics: Campylobacter Infections; Campylobacter rectus; Empyema, Pleural; Humans; RNA, Ribosomal, 16S; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

PubMed: 34645758
DOI: 10.2169/internalmedicine.7704-21

Review

Authors: Charles M Cobb, Patricia J Kelly, Karen B Williams...

Significant evidence supports an association between periodontal pathogenic bacteria and preterm birth and preeclampsia. The virulence properties assigned to specific oral pathogenic bacteria, for example, , , , , and others, render them as potential collaborators in adverse outcomes of pregnancy. Several pathways have been suggested for this association: 1) hematogenous spread (bacteremia) of periodontal pathogens; 2) hematogenous spread of multiple mediators of inflammation that are generated by the host and/or fetal immune response to pathogenic bacteria; and 3) the possibility of oral microbial pathogen transmission, with subsequent colonization, in the vaginal microbiome resulting from sexual practices. As periodontal disease is, for the most part, preventable, the medical and dental public health communities can address intervention strategies to control oral inflammatory disease, lessen the systemic inflammatory burden, and ultimately reduce the potential for adverse pregnancy outcomes. This article reviews the oral, vaginal, and placental microbiomes, considers their potential impact on preterm labor, and the future research needed to confirm or refute this relationship.

PubMed: 28848365
DOI: 10.2147/IJWH.S142730