Differential Virulence of Aggregatibacter actinomycetemcomitans Serotypes Explained by Exoproteome Heterogeneity

Fu, Yanyan; Maaß, Sandra; Cavallo, Francis M.; Jong, Anne de; Raangs, Erwin; Westra, Johanna; Buist, Girbe; Becher, Dörte; Dijl, Jan Maarten van

doi:10.1128/spectrum.03298-22

Cited by 4 publications

(6 citation statements)

References 98 publications

(125 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a robust immunoregulator of the alveolar bone homeostasis and the periodontal immune system, Aa plays a role in the most aggressive types of periodontitis [15]. The serotypes of Aa are defined based on the antigenicity of the O‐polysaccharide component of the LPS, with a, b, and c, as the most frequent serotypes in adult individuals [12].…”

Section: Aggregatibacter Actinomycetemcomitans (Aa)mentioning

confidence: 99%

“…The disease's symptoms generally manifest as mild memory problems and progress to cognitive deficits, dysfunction in challenging daily tasks, and other cognitive issues. The yet-unknown pathophysiology of AD can be elucidated by high peptide levels caused by an imbalance between its production and clearance, which leads to the beta-amyloid peptide (Aβ) [12] accumulation or Amyloid-cascade [13,14]. Anatomopathologically, AD is characterized by two quintessential lesions.…”

Section: Importance Pathophysiology Etiology and Epidemiologymentioning

confidence: 99%

“…Cognitive disorders and AD are associated with poor dental conditions as late-life markers of the cumulative impacts of oral inflammatory pathologic diseases such as periodontitis [64]. AD is pathologically characterized by senile plaques comprising amyloid-β [12] and NFTs formed by P-tau [22,60,65]. Research suggests spirochetes can be isolated as a source of Aβ from the brain tissue of patients with AD [65].…”

Section: T Denticola and Admentioning

confidence: 99%

“…Anatomopathologically, AD is characterized by two quintessential lesions. The first type is senile plaques as extracellular lesions made up of a nucleus of Aβ accumulation, and the second includes intraneuronal neurofibrillary tangles (NFTs), which are made of hyperphosphorylated tau protein (P‐tau) [12].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The role of periodontitis‐associated bacteria in Alzheimer's disease: A narrative review

et al. 2023

View full text Add to dashboard Cite

Alzheimer's disease causes memory loss and dementia in older adults through a neurodegenerative mechanism. Despite the pathophysiological clarification of this cognitive disorder, novel molecular and cellular pathways should be identified to determine its exact mechanism. Alzheimer's disease (AD) is pathologically characterized by senile plaques comprising beta‐amyloid and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau as a microtubule‐associated protein with a key role in the pathogenesis of AD. Periodontitis through inflammatory pathways is a risk factor for deteriorating cognitive impairment in AD patients. Poor oral hygiene coupled with immunocompromised status in older adults causes periodontal diseases and chronic inflammations through an oral bacterial imbalance. Toxic bacterial products, including bacteria themselves, can reach the central nervous system through the bloodstream and evoke inflammatory responses. The present review was conducted to investigate relationships between AD and periodontitis‐involved bacteria as a risk factor.

show abstract

Section: Aggregatibacter Actinomycetemcomitans (Aa)mentioning

confidence: 99%

Section: Importance Pathophysiology Etiology and Epidemiologymentioning

confidence: 99%

Section: T Denticola and Admentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The role of periodontitis‐associated bacteria in Alzheimer's disease: A narrative review

et al. 2023

View full text Add to dashboard Cite

show abstract

“…In B. subtilis , HtrA and its cross-regulated paralog HtrB counteract secretion stress ( 4 , 5 , 7 ). In bacterial pathogens, HtrA-like proteases are crucial for survival in host organisms, which makes them interesting targets for treatment ( 11 – 13 ). In humans, HtrA family proteases are implicated in pathological conditions, such as cancer and Parkinson’s or Alzheimer’s disease ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Enhancing bacterial fitness and recombinant enzyme yield by engineering the quality control protease HtrA of Bacillus subtilis

Öktem,

Núñez-Nepomuceno,

Ferrero-Bordera

et al. 2023

Microbiol Spectr

Self Cite

View full text Add to dashboard Cite

Bacillus subtilis is a Gram-positive bacterium that is well-known for its high secretory capacity. Although secretion of homologous proteins is extremely efficient, secretion of heterologous proteins imposes what is known as “secretion stress” on the cells. This is not desirable in an industrial setting, because the bacterial secretion stress responses can adversely affect product yields. So far, the main approach to reduce such counterproductive secretion stress responses has been to remove components of the CssR-CssS two-component regulatory system, including the CssR-CssS-regulated quality control proteases HtrA and/or HtrB. However, there are several examples indicating that a complete loss of these proteases does not correlate with improved protein secretion or a reduced secretion stress response. In this study, an alternative approach to limit the effects of secretion stress by modulating the protease activity of HtrA rather than completely removing this protease was investigated. Indeed, expression of the proteolytically inactive HtrA led to a generally improved fitness of the bacteria when producing the heterologous α-amylase AmyQ. Moreover, compared to control strains, the strain expressing the mutant HtrA provided higher AmyQ yields, which correlated with superior α-amylase enzymatic activity in shake flasks and fermenter-scale cultivations. Proteome analysis of the engineered strains revealed critical differences in stress responses and metabolism. Altogether, our present findings show how proteolytically inactive HtrA can be employed to achieve improved bacterial fitness and higher enzyme yields. IMPORTANCE In the expanding market of recombinant proteins, microbial cell factories such as Bacillus subtilis are key players. Microbial cell factories experience secretion stress during high-level production of secreted proteins, which can negatively impact product yield and cell viability. The CssRS two-component system and CssRS-regulated quality control proteases HtrA and HtrB play critical roles in the secretion stress response. HtrA has a presumptive dual function in protein quality control by exerting both chaperone-like and protease activities. However, its potential role as a chaperone has not been explored in B. subtilis . Here, we describe for the first time the beneficial effects of proteolytically inactive HtrA on α-amylase yields and overall bacterial fitness.

show abstract

Understanding protein secretion stress in Bacillus subtilis for biotechnological applications

Öktem

View full text Add to dashboard Cite

The biopharmaceuLcal market is growing faster than ever with two producLon systems compeLng for market dominance: mammalian cells and microorganisms. In recent years, based on the rise of anLbody-based therapies, new biotherapeuLc approvals have favored mammalian hosts. However, extensive research has elevated our understanding of microbes to new levels and emerging therapeuLc molecules facilitate their use, and so the quesLon has to be asked: is it Lme microbes fight back? This review aims to answer this Lmely quesLon by cross-comparing four microbial producLon hosts and examining the innovaLons made to both their secreLon and post-translaLonal modificaLon capabiliLes. Furthermore, the impact of tools such as omics and systems biology, as well as alternaLve producLon systems and emerging biotherapeuLcs are discussed.

show abstract

Differential Virulence of Aggregatibacter actinomycetemcomitans Serotypes Explained by Exoproteome Heterogeneity

Cited by 4 publications

References 98 publications

The role of periodontitis‐associated bacteria in Alzheimer's disease: A narrative review

The role of periodontitis‐associated bacteria in Alzheimer's disease: A narrative review

Enhancing bacterial fitness and recombinant enzyme yield by engineering the quality control protease HtrA of Bacillus subtilis

Understanding protein secretion stress in Bacillus subtilis for biotechnological applications

Contact Info

Product

Resources

About