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Journal: Prevalence of the oral pathogen Filifactor alocis and its FtxA toxin related to clinical parameters and presence of Aggregatibacter actinomycetemcomitans. (Pubmed Central) - Feb 6, 2025
The Gram-positive organism Filifactor alocis is implicated in multiple oral diseases including periodontitis, and approximately 50% of known strains encode and produce a recently identified repeat-in-toxin (RTX) protein, FtxA, partly homologous to the Aggregatibacter actinomycetemcomitans leukotoxin...Moreover, among the individuals carrying A. actinomycetemcomitans, a majority also exhibited an ftxA-positive F. alocis, supporting the notion of the synergistic behavior of these two species. This emphasizes that F. alocis and its ftxA are involved in the pathogenesis of periodontitis and may have ecological roles, with diagnostic and prognostic implications for the disease.
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Journal: Whole genome sequencing revealed high proportions of ST152 MRSA among clinical Staphylococcus aureus isolates from ten hospitals in Ghana. (Pubmed Central) - Dec 19, 2024
Virulence genes for enterotoxins, biofilms, toxic-shock-syndrome toxins, hemolysins, and leukotoxins were also detected...Our findings highlight the predominance of pandemic clones, particularly ST152, and the notable transition of ST152 MSSA to ST152 MRSA over the past decade. The findings from this study supports AMR surveillance efforts in Ghana and emphasize the importance of implementing genomic surveillance using WGS to comprehensively monitor the rise and spread of multi-drug-resitant organisms such as MRSA in the country.
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Review, Journal: The Oral Microbiota, Microbial Metabolites, and Immuno-Inflammatory Mechanisms in Cardiovascular Disease. (Pubmed Central) - Nov 27, 2024
The potential mechanisms by which the oral microbiota can influence CVD development include oral and systemic inflammation, immune responses, cytokine release, translocation of oral bacteria into the bloodstream, and the impact of microbial-related products such as microbial metabolites (e.g., short-chain fatty acids [SCFAs], trimethylamine oxide [TMAO], hydrogen sulfide [H2S], nitric oxide [NO]) and specific toxins (e.g., lipopolysaccharide [LPS], leukotoxin [LtxA])...Integrated multi-omics methodologies, along with large-scale longitudinal population studies and intervention studies, will facilitate a deeper understanding of the metabolic and functional roles of the oral microbiome in cardiovascular health. This fundamental knowledge will support the development of targeted interventions and effective therapies to prevent or reduce the progression from cardiovascular risk to clinical CVD events.
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Clinical, Journal: Effectiveness of an experimental subunit ovine Mannheimia haemolytica respiratory vaccine in reducing pneumonia in lambs. (Pubmed Central) - Sep 2, 2024
The effectiveness of an experimental subunit Mannheimia haemolytica leukotoxin A (LtxA) and transferrin binding protein B (TbpB) vaccine was evaluated in lambs for reduction of clinical disease in an experimental challenge study and in a controlled randomized field trial in a large commercial sheep operation...Although vaccination with the experimental subunit M. haemolytica vaccine induced high LtxA and TbpB antibodies, it did not reduce clinical disease in lambs following an experimental challenge study or in a controlled randomized field trial in a commercial sheep operation. Further research is required to identify additional protective antigens for a safe and effective ovine respiratory vaccine to reduce pneumonia losses in commercial sheep flocks.
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Journal: Effective degradation of various bacterial toxins using ozone ultrafine bubble water. (Pubmed Central) - Jul 10, 2024
This study revealed that OUFBW treatment abolished the toxicity of pneumolysin, a pneumococcal pore-forming toxin, and leukotoxin, a toxin that causes leukocyte injury...Additionally, OUFBW exerted bactericidal activity against Staphylococcus aureus, including an antibiotic-resistant strain, without displaying significant toxicity toward human neutrophils or erythrocytes. These results suggest that OUFBW not only sterilizes bacteria but also degrades bacterial toxins.
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Journal: Presence and Immunoreactivity of Aggregatibacter actinomycetemcomitans in Rheumatoid Arthritis. (Pubmed Central) - May 24, 2024
The primary aim of the present study is to examine the correlation between the presence of Aggregatibacter actinomycetemcomitans (Aa) in the oral cavity and serum antibodies against the leukotoxin (LtxA) produced by this bacterium...We conclude that a systemic immune response to Aa LtxA does not fully reflect the prevalence of Aa in saliva. In addition, the association between RA-associated parameters and the presence of Aa was negligible in the present RA cohort.
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Review, Journal: Therapeutic Applications of Aggregatibacter actinomycetemcomitans Leukotoxin. (Pubmed Central) - May 24, 2024
In addition to serving as an important virulence factor for the bacterium, because of its exquisite specificity and rapid activity, LtxA is also being investigated as a therapeutic agent that may be used to treat diseases such as hematological malignancies and autoimmune/inflammatory diseases. It is our hope that this review will inspire an increased intensity of research related to LtxA and its effect on Aggressive Periodontitis, the disease that led to its initial discovery.
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Journal, Gram negative: Toxin-triggered liposomes for the controlled release of antibiotics to treat infections associated with the gram-negative bacterium, Aggregatibacter actinomycetemcomitans. (Pubmed Central) - May 9, 2024
In the current study, we developed a toxin-triggered liposomal antibiotic delivery system, in which the drug release is enabled by the leukotoxin (LtxA) produced by the Gram-negative pathogen, Aggregatibacter actinomycetemcomitans...Finally, we showed that antibiotic release occurs selectively in the presence of an LtxA-producing strain of A. actinomycetemcomitans but not in the presence of a non-LtxA-expressing strain. Together, these results demonstrate that the designed liposomal vehicle enables toxin-triggered delivery of antibiotics to LtxA-producing strains of A. actinomycetemcomitans.
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Journal, Heterogeneity: Heterogeneity of Size and Toxin Distribution in Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles. (Pubmed Central) - Mar 31, 2024
The strains of A. actinomycetemcomitans most closely associated with disease produce more of a secreted leukotoxin (LtxA) than isolates from healthy carriers, suggesting a key role for this toxin in disease progression...Our results indicate that surface-associated DNA drives the selective sorting of LtxA into large OMVs. This study provides valuable insights into the observed heterogeneity of A. actinomycetemcomitans vesicles and emphasizes the importance of understanding these variations in the context of bacterial pathogenesis.
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Preclinical, Journal: Staphylococcus aureus Panton-Valentine Leukocidin worsens acute implant-associated osteomyelitis in humanized BRGSF mice. (Pubmed Central) - Mar 20, 2024
Immune evasion of S. aureus relies on various mechanisms to survive within the bone niche, including the secretion of leukotoxins such as Panton-Valentine leukocidin (PVL)...Expectedly, a smaller fraction of human myeloid cells were apoptotic in the ?pvl-infected huBRGSF animals. Taken together, our study highlights the pivotal role of PVL during acute implant-associated osteomyelitis in humanized mice.
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Functional Neutrophil Phenotypes in Murine Models of Acute Lung Injury (San Diego Convention Center, Area I (Hall H, Ground Level)) - Mar 17, 2024 - Abstract #ATS2024ATS_9124;
The suppressed phenotype in severe and late ALI depends on soluble thermostable factors in the bronchoalveolar microenvironment. Future studies will aim to identify these factors and better characterize the functional and transcriptomic states of different neutrophil phenotypes during ALI.
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Targeted delivery of antibiotics to treat infections associated with Gram-negative bacteria using a toxin-triggered liposomal system (Hybrid; Gravier C Ballroom (New Orleans Marriott Warehouse Arts District)) - Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_12277;
In this study, we developed a toxin-triggered liposomal antibiotic delivery system, in which the drug release is achieved through binding by leukotoxin (LtxA), a toxin produced by the Gram-negative pathogen, Aggregatibacter actinomycetemcomitans...Finally, we showed that antibiotic release occurs selectively in the presence of an LtxA-producing strain of A. actinomycetemcomitans but not in the presence of a non-LtxA-expressing strain. Together, these results demonstrate that our developed liposomal vehicle enables toxin-triggered delivery of antibiotics to LtxA-producing strains of A. actinomycetemcomitans .
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Journal: Genomic characteristics of cfr and fexA carrying Staphylococcus aureus isolated from pig carcasses in Korea. (Pubmed Central) - Feb 21, 2024
Moreover, the strains carried enterotoxin gene clusters, including the hemolysin, leukotoxin, and protease genes, which are associated with humans or livestock...Strains carrying the plasmid replicon repUS5 displayed high sequence similarity (99%) to the previously reported strain pSA737 in human clinical samples in the United States. The results illustrate the need for continuous monitoring of the prevalence and transmission of linezolid-resistant S. aureus isolated from animals and their products.
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Preclinical, Journal: Identification, Biochemical Characterization, and In Vivo Detection of a Zn-Metalloprotease with Collagenase Activity from Mannheimia haemolytica A2. (Pubmed Central) - Jan 31, 2024
haemolytica can secrete several virulence factors, such as leukotoxin, lipopolysaccharide, and proteases, that can be targeted to treat infections...Finally, the antibodies were used to perform immunohistochemical tests on postmortem lung samples from sheep with suggestive histology data of pneumonic mannheimiosis. Taken together, our results strongly suggest that the 110-Mh metalloprotease participates as a virulence mechanism that promotes damage to host tissues.
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Journal: Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica. (Pubmed Central) - Oct 4, 2023
In an effort to develop a vaccine candidate targeting a primary bacterial agent contributing to BRD, we produced a tripartite antigen consisting of segments of the virulence factor Leukotoxin A (LktA) and lipoprotein PlpE from Mannheimia haemolytica, fused to a cholera toxin mucosal adjuvant (CTB)...Moreover, the antigen remained stable at room temperature with limited deterioration for up to one year when stored as lyophilized plant material. This study demonstrated that a recombinant antigen expressed in plant tissue elicited both humoral and mucosal immune responses when fed to mice, and warrants evaluation in cattle.
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Journal: Outer-Membrane Vesicles of Fusobacterium necrophorum: A Proteomic, Lipidomic, and Functional Characterization. (Pubmed Central) - Aug 26, 2023
The OMPs and toxins were among the proteins with the highest intensity identified, including the 43-kDa-OMP-, OmpA-, and OmpH-family proteins, the cell-surface protein, the FadA adhesin protein, the leukotoxin-LktA-family filamentous adhesin, the N-terminal domain of hemagglutinin, and the OMP transport protein and assembly factor...The lactate-dehydrogenase-cytotoxicity assays showed that the OMVs had a high degree of cytotoxicity against a bovine B-lymphocyte cell line (BL-3 cells). Thus, our data suggest the need for further studies to evaluate the ability of OMVs to induce immune responses and assess their vaccine potential in vivo.
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Journal: The role of NLRP3 in regulating gingival epithelial cell responses evoked by Aggregatibacter actinomycetemcomitans. (Pubmed Central) - Aug 11, 2023
actinomycetemcomitans) has myriads of virulence factors among which leukotoxin provides A. actinomycetemcomitans with the advantage to thrive in the surrounding hostile environment and evade host immune defences...Of the 37 proteins, 23 of these inflammation-related proteins released by NLRP3-deficient cells differed significantly compared to Cas9 cells after infection. This suggests that NLRP3 has a broad effect on the inflammatory response in gingival epithelial cells.
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Review, Journal: A genetic regulatory see-saw of biofilm and virulence in MRSA pathogenesis. (Pubmed Central) - Jul 12, 2023
The up- and downregulation of adhesion genes involved in biofilm formation and genes responsible for synthesizing virulence factors during different stages of infection act as a genetic regulatory see-saw in the pathogenesis of MRSA. This review provides insight into the evolution and pathogenesis of MRSA infections with a focus on genetic regulation of biofilm formation and virulence factors secretion.
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Journal: Pathogenic potential and antimicrobial resistance of Staphylococcus pseudintermedius isolated from human and animals. (Pubmed Central) - Apr 18, 2023
All isolates tested had the exfoliating toxin gene and the leukotoxin determining genes, but only the human strains had enterotoxin genes...The considerable genetic diversity of strains from a limited geographical area indicates the processes of change taking place within this species. Thus, careful observation of the ongoing process of variation is necessary, as they may lead to the selection of S. pseudintermedius, which will pose a significant threat to humans.
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Journal: Comparative protection of small ruminants against Mannheimia haemolytica infection by inactivated bacterin and toxoid vaccines. (Pubmed Central) - Mar 1, 2023
The evaluation was based on antibody responses to vaccination in sheep and goats for both bacteria and leukotoxin...This study highlighted the effectiveness of adding a bacterial toxoid in the vaccine as a promising solution for preventing mannheimiosis in small ruminants. Because of the worldwide distribution of M. haemolytica infection, general prophylaxis based on a combined inactivated vaccine could greatly benefit.
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Journal: Decreased oxidative stress and altered urinary oxylipidome by intravenous omega-3 fatty acid emulsion in a randomized controlled trial of older subjects hospitalized for COVID-19. (Pubmed Central) - Dec 13, 2022
The randomized controlled single-blind trial COVID-Omega-F showed that intravenous omega-3 polyunsaturated fatty acids (n-3 PUFA) shifted the plasma lipid signature of COVID-19 towards increased proresolving precursor levels and decreased leukotoxin diols, associated with a beneficial immunodulatory response...The oxidative stress marker 15-F-isoprostane was significantly lower in patients receiving n-3 PUFA treatment, who also exhibited significantly decreased erythrocyte oxidative stress compared with placebo-treated patients. These findings point to additional beneficial effects of intravenous n-3 PUFA emulsion treatment through a beneficial oxylipid profile and decreased oxidative stress in COVID-19.
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Review, Journal: Prognosis in substance abuse-related acute toxic leukoencephalopathy: A scoping review. (Pubmed Central) - Oct 28, 2022
These findings point to additional beneficial effects of intravenous n-3 PUFA emulsion treatment through a beneficial oxylipid profile and decreased oxidative stress in COVID-19. Substance abuse-related acute TL often has a poor prognosis, but partial or even full recovery is possible in a subgroup of individuals over months to years.
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Search the medical literature for papers on the effects of acrolein, 4hne, 13 hode, 9 hode, leukotoxin diol, 9 ona, 2 ag, oxidized cardiolipin, oxidized ldl, malondialdehyde, or oxlams (oxidized linoleic acid metabolities) (Twitter) - Oct 26, 2022
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Preclinical, Journal: Blockade of the Adenylate Cyclase Toxin Synergizes with Opsonizing Antibodies to Protect Mice against Bordetella pertussis. (Pubmed Central) - Sep 3, 2022
Despite mediating immune-evasive functions as a leukotoxin, ACT's potential role as a protective antigen is unclear...Using a murine infection model, we show that antibodies neutralizing ACT can contribute to protection against infection through synergistic interactions with antibodies recognizing current vaccine antigens. Our data can help guide the design of future vaccines, whereby the inclusion of ACT-based immunogens might increase protection against pertussis infection.
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Journal: Structural basis for non-canonical integrin engagement by Bordetella adenylate cyclase toxin. (Pubmed Central) - Aug 22, 2022
Integrins are ubiquitous cell-surface heterodimers that are exploited by pathogens and toxins, including leukotoxins that target β integrins on phagocytes...Furthermore, binding to αβ positions the essential ACT acylation sites, which are conserved among toxins exported by type I secretion systems, at the cell membrane. These findings reveal a structural mechanism for integrin-mediated attachment and explain antibody-mediated neutralization of ACT intoxication.
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Preclinical, Journal: Transcriptome change of Staphylococcus aureus in infected mouse liver. (Pubmed Central) - Jul 23, 2022
For example, hemolysins, but not leukotoxins and serine proteases, were highly upregulated at 6 h.p.i...Hypoxia response genes were upregulated at 24 and 48 h.p.i., and immune response genes were upregulated from 6 h.p.i. These findings suggest that gene expression of S. aureus in the host changes in response to changes in the host environment, such as the oxygenation status or immune system attacks during infection.
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Preclinical, Journal: Galacto-oligosaccharides alleviate lung inflammation by inhibiting NLRP3 inflammasome activation in vivo and in vitro. (Pubmed Central) - Jul 9, 2022
These findings suggest that gene expression of S. aureus in the host changes in response to changes in the host environment, such as the oxygenation status or immune system attacks during infection. GOS exert anti-inflammatory properties by inhibiting the NLRP3 inflammasome activation in vitro and in vivo, suggesting a potential role for GOS in the prevention of lung infections.
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Journal: Computational modeling and druggability assessment of Aggregatibacter actinomycetemcomitans leukotoxin. (Pubmed Central) - Jul 8, 2022
The resulting model was refined by energy minimization, validated by Molprobity and ProSA tools, and subsequently subjected to a cumulative 600ns of all-atom classical molecular dynamics simulation to evaluate its structural aspects. The druggability of the proposed model was assessed using Fpocket and FTMap tools, resulting in the identification of four putative cavities and fifteen binding hotspots that could be targeted by rational drug design tools to find new ligands to inhibit LtxA activity.
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