Leukothera (leukotoxin) / Actinobac Biomed - LARVOL DELTA

Antibodies to Periodontal Bacteria Are Associated with Systemic Lupus Erythematosus and Autoantibody Positivity. (PubMed, Int J Mol Sci) - "Serum IgG antibodies against P. gingivalis, A. actinomycetemcomitans leukotoxin A (LtxA), and two control bacteria (Capnocytophaga ochracea and Escherichia coli) were quantified in 223 patients with SLE and 301 healthy controls...Elevated levels of antibodies against P. gingivalis and A. actinomycetemcomitans in patients with SLE suggest a role for these bacteria, or periodontitis, in the immunopathogenesis of SLE. An additive interaction with smoking was observed for P. gingivalis, and A. actinomycetemcomitans exposure was associated with anti-DSNA antibody positivity, supporting a link between these bacteria and SLE."

Journal • Dental Disorders • Immunology • Inflammatory Arthritis • Lupus • Periodontitis • Systemic Lupus Erythematosus

Identification of genes that differentiate Mannheimia haemolytica genotypes 1 and 2 using a pangenome approach. (PubMed, PLoS One) - "Genotype differentiating genes included genotype-associated variants of a TonB-dependent siderophore receptor homolog, transferrin binding protein B, leukotoxin A, and IgA1 proteases...Genotype 2 genomes were significantly larger in size and contained more predicted protein coding genes than genotype 1 genomes. These results expand our knowledge of what differentiates the genotypes 1 and 2 of M. haemolytica and provides information that can be used as the basis for laboratory investigations of corresponding phenotypic differences."

Journal • Respiratory Diseases

THE LINOLEIC ACID-DERIVED LEUKOTOXIN 9,10-DIHOME DRIVES IMMUNOSUPPRESSION IN PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE (AASLD 2025) - "Taken together, these findings indicate that increased circulating levels of the leukotoxin 9,10-DiHOME weakens immune-cell defensive responses, thus enhancing the susceptibility of AD patients to bacterial infection and precipitating ACLF. These data also position sEH as an actionable drug target in this condition."

Clinical • Fibrosis • Hepatology • Immunology • Infectious Disease • Liver Failure • MERTK

A modified-live Mannheimia haemolytica expressing Mycoplasma bovis EFTu and Hsp70 induced systemic and mucosal antibody responses in American bison but failed to fully protect against Mycoplasma bovis challenge. (PubMed, Vet Microbiol) - "haemolytica) vaccine strains, serotypes 1 and 6, secreting inactive leukotoxin fused to truncated M. bovis Elongation Factor Thermal unstable (EFTu) and Heat shock protein (Hsp) 70 (EFTu-Hsp70-ΔlktCAV4) were evaluated for efficacy in bison...Despite this, fewer M. bovis positive tissue swabs were collected from animals administered the M. haemolytica EFTu-Hsp70-ΔlktCAV4. These results demonstrate that modified-live M. haemolytica vaccine strains expressing M. bovis antigens failed to provide full protection against M. bovis infection in bison."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Comparison of Total IgG and Neutralizing Antibody Responses to a Novel Trivalent Recombinant Mannheimia haemolytica Vaccine Containing Serotype 6. (PubMed, Microb Pathog) - "While leukotoxin (LKT) is a common vaccine target, serotype-1 specific antigen (SSA-1) is often overlooked...Challenge studies further corroborated the stimulation of nAbs. The trivalent vaccine effectively stimulated both total IgG and nAb responses against all three serotypes in mice, suggesting its potential for broad protection against M. haemolytica."

Journal • Review • Infectious Disease

Core genome multilocus sequence typing (cgMLST) indicates herd specificity of Fusobacterium necrophorum ssp. necrophorum isolated from dairy cattle interdigital phlegmon outbreaks in Finland. (PubMed, Vet Microbiol) - "All isolates harboured virulence genes for leukotoxin and haemolysin but were devoid of adhesin...necrophorum in IP cows from Finnish dairy cattle herds. Therefore, the cause of IP outbreaks in Finland remains unknown and merits further research."

Journal

Contribution of Leukocidin ED to the Pathogenesis of Staphylococcus aureus Endophthalmitis. (PubMed, Invest Ophthalmol Vis Sci) - "LukED does not seem to be essential for the pathogenesis of experimental S. aureus endophthalmitis. However, other leukotoxins are expressed in vivo, which may compensate for the effects of LukED during infection."

Journal • Infectious Disease • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology

Design of a multi-epitope vaccine against Staphylococcus Aureus lukotoxin ED using in silico approaches. (PubMed, Sci Rep) - "B cell and helper T lymphocyte (HTL) epitopes of leukotoxin ED (LukED) were predicted using computational tools...We have designed vaccine against S. aureus LukED that targets epitope-rich regions, which helps maintain a native-like conformation. This work lays the groundwork for further experimental studies to evaluate the vaccine's neutralizing effects."

Journal • TLR1

Mannheimia haemolytica isogenic capsular and LPS-sialylation gene deletion mutants are attenuated in a calf lung challenge model. (PubMed, Microbiol Spectr) - "The reduced clinical signs, pneumonic lung lesions, and bacterial recovery in the lungs of the calves challenged with either the Δcap or the ΔneuA M. haemolytica mutant strains indicated that these mutations were significantly less virulent than the parent strain.IMPORTANCEWhile Mannheimia haemolytica leukotoxin is well recognized as a major virulence factor, the roles of other possible virulence factors, such as capsule and sialic acid (sialylation of LPS) in M. haemolytica, have not been investigated in animal models. This study revealed that the abolishment of capsule (Δcap) or LPS sialylation (ΔneuA) significantly reduced the virulence of each mutant in calf lung challenges. These results demonstrate that both M. haemolytica capsule and sialylated LPS are important virulence factors that play a key role in the evasion of host defenses."

Journal • Hematological Disorders • Infectious Disease • Pneumonia • Respiratory Diseases

Immunogenicity and protective efficacy of seven candidate vaccines boosted with recombinant proteins, whole-cell bacterins of three serotypes of Mannheimia haemolytica, and an emulsion-type adjuvant. (PubMed, Front Vet Sci) - "Recombinant leukotoxin (lkt) and S1-specific antigen (SSA-1) proteins were produced and used in the development of both vaccines and in-house ELISA...The trivalent S6 vaccine with Montanide™ ISA 206 shows promise for improved protection against diverse M. haemolytica strains. Further research, including challenge studies in target animals, is needed to confirm these findings and evaluate field efficacy."

Journal • Infectious Disease • Respiratory Diseases

CO-CARRIERSHIP OF HERPES SIMPLEXVIRUS AND AGGREGATIBACTER ACTINOMYCETEMCOMITANS LEUKOTOXIN ASSOCIATED WITH DECLINING HIPPOCAMPAL VOLUMES IN HEALTHY ELDERLY ADULTS (ADPD 2025) - "Concurrent carriership of HSV -1 and the A. actinomycetemcomitans Ltxa may be associated with 5-year hippocampal atrophy among 75 -year-olds."

Clinical • Herpes Simplex • Inflammation

Polyunsaturated Fatty Acid Imbalance-A Contributor to SARS CoV-2 Disease Severity. (PubMed, J Nutr Metab) - "Therapeutic treatment of SARS CoV-2 patients with ω-3 PUFA significantly increased 18-HEPE (SPM precursor) and EPA-derived diols (11,12- and 14,15-diHETE), while toxic 9,10- and 12,13-diHOMEs (leukotoxin and iosleukotoxin, respectively) decreased. Unbalanced dietary intake of ω-6/ω-3 PUFAs contributed to SARS CoV-2 disease severity by decreasing ω-3-dependent SPM resolution of inflammation and increasing membrane-associated ferroptotic AA peroxidation."

Journal • Review • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Prevalence of the oral pathogen Filifactor alocis and its FtxA toxin related to clinical parameters and presence of Aggregatibacter actinomycetemcomitans. (PubMed, Front Cell Infect Microbiol) - "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."

Journal • Dental Disorders • Infectious Disease • Periodontitis

Development of high-performance inducible and secretory expression vector and host system for enhanced recombinant protein production. (PubMed, Sci Rep) - "Using the pKS81 plasmid, we successfully achieved high yields of prokaryotic (staphylococcal leukotoxin E) and eukaryotic (human annexin A2 protein tagged with mouse IgG1) recombinant proteins, up to 900 mg/L. Our newly established inducible and secretory expression system provides for efficient production and easy purification of LPS-free recombinant proteins, making it valuable for biomedical research and industrial applications."

Journal • Infectious Disease • ANXA2

Complete genome sequence of a penicillin-resistant Fusobacterium necrophorum subsp. funduliforme isolate from a tonsillitis patient. (PubMed, Microbiol Resour Announc) - "funduliforme isolate, AJ79, from a tonsillitis patient. The AJ79 genome consists of a chromosome (2,440,359 bp) and plasmid (9,887 bp), providing insights into the genetic basis of penicillin resistance in F. necrophorum and its implications for treating tonsillitis."

Journal • Infectious Disease • Otorhinolaryngology

The Oral Microbiota, Microbial Metabolites, and Immuno-Inflammatory Mechanisms in Cardiovascular Disease. (PubMed, Int J Mol Sci) - "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."

Journal • Review • Atherosclerosis • Cardiovascular • Dental Disorders • Dyslipidemia • Gastrointestinal Disorder • Inflammation • Periodontitis

Whole genome sequencing revealed high proportions of ST152 MRSA among clinical Staphylococcus aureus isolates from ten hospitals in Ghana. (PubMed, mSphere) - "Other predominant resistance genes included tetK (46%), cat (42%), and dfrG (36%) encoding resistance for tetracyclines, phenicols, and diaminopyrimidine, respectively. 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."

Journal • Infectious Disease • Septic Shock

Impact of CCR5Δ32 on the risk of infection, Staphylococcus aureus carriage, and plasma concentrations of chemokines in Danish blood donors. (PubMed, EBioMedicine) - "Results from this CCR5Δ32 high-prevalent cohort do not support the idea that CCR5Δ32 affects the risk of S. aureus carriage or infection to any relevant degree, in this northern European context. CCL4 was the main chemokine affected by CCR5Δ32 and was observed in higher concentration among Δ32-carriers. This study cannot rule out that S. aureus is a previous driver of CCR5Δ32 selection."

Journal • Allergy • Human Immunodeficiency Virus • Immunology • Infectious Disease • CCL11 • CCL2 • CXCL10

Effectiveness of an experimental subunit ovine Mannheimia haemolytica respiratory vaccine in reducing pneumonia in lambs. (PubMed, Can Vet J) - "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."

Clinical • Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Virulence and host specificity of staphylococci from Staphylococcus intermedius group of pigeon origin with an emphasis on Staphylococcus intermedius. (PubMed, Microb Pathog) - "We proved that pigeon strains carried genes encoding for exfoliative toxin SIET and leukotoxin Luk-I...Moreover, only S. intermedius was not able to invade canine keratinocytes at all. These findings highlight the complex interplay between SIG bacteria, and their hosts, underscoring the need for further research to understand the mechanisms of host adaptation and pathogenicity within this group."

Journal

Distribution of virulence genes in clinical isolates of hospital-associated and community-associated methicillin-susceptible Staphylococcus aureus from Terengganu, Malaysia. (PubMed, Trop Biomed) - "The most frequent virulence genes detected were hla (78.9%, n=86) and hld (78.0%, n=85) encoding hemolysins, lukED (56.9%, n=62) encoding leukotoxin ED, followed by seb (26.6%, n=29) and sea (24.8%, n=27) encoding enterotoxins...However, there is no significant association between virulence genes among the different types of infection. The clinical MSSA isolates in Terengganu showed high prevalence and high diversity of virulence gene carriage."

Journal • Infectious Disease

Apo-Lactoferrin Inhibits the Proteolytic Activity of the 110 kDa Zn Metalloprotease Produced by Mannheimia haemolytica A2. (PubMed, Int J Mol Sci) - "haemolytica secretes leukotoxin, lipopolysaccharides, and proteases, which may be targeted to treat infections...Our results showed that apo-bLf inhibited the secretion and activity of the 110-Mh metalloprotease. Molecular docking and overlay assays showed that apo-bLf bound near the active site of the 110-Mh metalloprotease, which affected its enzymatic activity."

Journal • Infectious Disease • Respiratory Diseases

Aggregatibacter actinomycetemcomitans: From the Oral Cavity to the Heart Valves. (PubMed, Microorganisms) - "The presence of leukotoxin A (LtxA), which plays an important role in the pathogenicity of the bacterium, has been associated with both periodontitis and the etiology of rheumatoid arthritis (RA)...In addition, A. actinomycetemcomitans possesses many virulence factors that contribute to its potential to cause cancer. This article provides an overview of the virulence factors of A. actinomycetecomitans and its association with various systemic diseases, its oncogenic potential, and the treatment options for infections caused by A. actinomycetecomitans."

Journal • Review • Cardiovascular • Dental Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Oncology • Periodontitis • Rheumatoid Arthritis • Rheumatology • IL1B • TNFA

Identification of linear B cell epitopes on the leukotoxin protein of Fusobacterium necrophorum. (PubMed, Anaerobe) - "In summary, these results establish EP-3D7 as a conserved antigenic epitope of F. necrophorum leukotoxin. It could be valuable in the development of vaccines and diagnostic reagents for F. necrophorum epitopes."

Journal • Hepatology

Effect of toxins from different periodontitis-associated bacteria on human platelet function. (PubMed, Mol Oral Microbiol) - "Although weak, the investigated toxins differently influenced human platelet function. LtxA and C14 mediated inhibitory effects, whereas LPS contributed to a slight activation of platelets. Further analysis of specific cellular responses mediated by bacterial toxins may render novel targets and suggestions for the treatment of periodontitis."

Journal • Dental Disorders • Infectious Disease • Inflammation • Periodontitis • SELP