Leukothera (leukotoxin) / Actinobac Biomed - LARVOL DELTA

Identification and phylogenetic analysis of Mannheimia haemolytica isolated from nasal samples of horses. (PubMed, Folia Microbiol (Praha)) - "The leukotoxin (lkt) gene was detected in only one (11.11%) Serotype 2 isolate...These findings indicate that M. haemolytica, including strains carrying virulence-associated markers, can be recovered from the upper respiratory tract of horses exhibiting respiratory disease. The exclusive recovery of M. haemolytica from clinically affected horses suggests a potential association with equine respiratory disease, although its causal role requires further investigation."

Journal • Anorexia • Infectious Disease • Pneumonia • Respiratory Diseases

Effect of a spore-based Mannheimia haemolytica vaccine on immune responses and respiratory microbiota in sheep. (PubMed, NPJ Vaccines) - "A chimeric protein (MhCP) containing neutralizing epitopes from leukotoxin A (NLKT) and outer membrane protein PlpE was expressed and adsorbed onto spores to produce Spore-MhCP, which was administered via two mucosal routes: intranasal and intragastric...From nasopharyngeal samples, 16S rRNA gene sequencing revealed 27 genera altered in the intranasal Spore-MhCP group, including a decrease in Mannheimia (days 14-35; p < 0.01). These findings indicate that intranasal Spore-MhCP enhances immunity and may reduce M. haemolytica proliferation in the upper respiratory tract, reducing lung infection risk."

Journal • Infectious Disease • Respiratory Diseases

Distribution and genetic diversity of Mannheimia species, including recently described taxa, in cattle in Japan. (PubMed, Infect Genet Evol) - "A newly developed PCR assay revealed that all isolates, except for one M. ruminalis isolate, one M. ruminalis-related isolate, and four M. bovis-related isolates, carried the lktA gene encoding leukotoxin, a major virulence factor...Notably, some isolates showing <98.65% 16S rRNA gene sequence similarity to known type strains may represent novel taxa, warranting taxonomic re-evaluation and phylogenetic reassessment within Mannheimia. Moreover, because many of these isolates harbor key virulence-associated genes linked to BRD, further studies are required to clarify the pathogenic potential of each species as opportunistic pathogens and their contribution to BRD."

Journal • Infectious Disease • Respiratory Diseases

Leukotoxin enhances nasopharyngeal colonization and shedding of Mannheimia haemolytica in bovine herpesvirus 1 infected calves. (PubMed, Res Vet Sci) - "These findings provide valuable insight into the nature of M. haemolytica infection in bovine hosts. They also indicate that leukotoxin expression may contribute to the competitive fitness M. haemolytica strains, potentially influencing their adaptation within the host."

Journal • Infectious Disease • Respiratory Diseases

Characterization of Virulence Factors, Biofilm Production, and Antimicrobial Resistance in Mastitis-Associated Staphylococcus aureus Strains by Phenotypic and Genotypic Methods. (PubMed, Foodborne Pathog Dis) - "Phenotypic analysis revealed hemolysin (55.55%) and coagulase production (36.11%), while molecular analysis revealed the presence of leukotoxin (luksF, 19.44%), hemolysin (hlb, 58.33%), coagulase (coa, 63.88%), and toxic shock syndrome toxin (tsst-1, 30.55%) genes...According to this study, S. aureus of mastitis origin harbors various virulence, antibiotic resistance, biofilm-forming, and efflux pump genes. Bovine mastitis-derived MDR S. aureus isolates can pose a significant public health risk and need urgent attention to formulate strategies for their control and preventing transfer to the human food chain."

Journal • Infectious Disease • Septic Shock

First genomic insights into multidrug-resistant Staphylococcus pseudintermedius from dogs in Vietnam. (PubMed, Comp Immunol Microbiol Infect Dis) - "Additionally, 20 virulence genes were identified, including those encoding intercellular adhesin, lipase, thermonuclease, adenosine synthase A, capsular polysaccharide synthesis, enterotoxins A and C, leukotoxins D and E, and lipoproteins involved in host cell entry and diacylglyceryl transferase...This study provides the first genomic insights into MDR S. pseudintermedius from dogs in Vietnam and highlights the emergence of novel genetic lineages. Continued surveillance is warranted to monitor the evolution and dissemination of these lineages."

Journal

The linoleic acid-derived leukotoxin 9,10-DiHOME drives immunosuppression in patients with acute-on-chronic liver failure. (PubMed, Hepatology) - "These findings indicate that increased levels of the leukotoxin 9,10-DiHOME weakens immune-cell defensive responses and position sEH as a potential drug target in ADC."

Journal • Fibrosis • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure • MERTK

Diversity and evolution of leukotoxin operons in Staphylococcus aureus. (PubMed, mSystems) - "In our study, we show that six leukotoxin operons in S. aureus are combined in different ways within each genome, which may contribute to the pathogen's ability to cause a myriad of diseases and colonize different tissue sites. Understanding the diversity and evolution of different leukotoxin genes will be critical to the development of anti-leukotoxin antibodies and immunization countermeasures that will effectively impede S. aureus infections."

Journal • Gastrointestinal Disorder • Infectious Disease • GLS2

Development and Evaluation of a P. multocida A-M. haemolytica A6-rLkt Combined Vaccine for Enhanced Control of Bovine Respiratory Disease Complex. (PubMed, Microb Pathog) - "This study aimed to develop and evaluate a novel combined vaccine that incorporates P. multocida A, M. haemolytica A6, and recombinant leukotoxin (rLkt), with the goal of enhancing immunogenicity and protective efficacy...The study highlights the effectiveness of the P. multocida - M. haemolytica - rLkt combined vaccine as a promising strategy for BRD control, emphasizing the advantages of multivalent vaccine designs in veterinary immunology. Future research should focus on large-scale trials to assess long-term efficacy and optimize vaccine delivery methods, ensuring enhanced protection and health outcomes in cattle populations."

Journal • Inflammation • Respiratory Diseases

Exploratory Study of Virulence Factors and Protein-Protein Interaction Networks in Major Oral Pathogens. (PubMed, Contemp Clin Dent) - "gingivalis), leukotoxin (A...Functional clustering revealed adhesion, peptidoglycan biosynthesis, and immune modulation pathways. PPI networks provide system-level mechanistic insights into pathogen virulence, revealing conserved vulnerabilities and species-specific mechanisms."

Journal • Dental Disorders • Immune Modulation • Immunology • Inflammation • Periodontitis • THRA

Aggregatibacter actinomycetemcomitans virulence factors and systemic inflammation: linking periodontitis to rheumatoid arthritis. (PubMed, J Oral Microbiol) - "Aa produces various virulence factors, including leukotoxin A (LtxA), lipopolysaccharide (LPS), and cytolethal distending toxin (CDT), enabling tissue invasion, inflammation, as well as modulation and evasion of immune responses...This review summarizes current knowledge on Aa virulence mechanisms and their potential contribution to systemic inflammation and autoimmunity. We propose Aa OMVs as possible link between PD and RA and offer new perspectives on therapeutic targeting of both diseases."

Journal • Review • Dental Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Periodontitis • Rheumatoid Arthritis • Rheumatology

E-cigarette liquids alter the biogenesis and properties of Aggregatibacter actinomycetemcomitans outer membrane vesicles. (PubMed, Front Cell Infect Microbiol) - "Through the secretion of outer membrane vesicles (OMVs), this bacterium establishes complex host-pathogen interactions, transmitting virulence determinants such as leukotoxin A (LtxA) that influence host cell behavior...SDS-PAGE showed significant differences in the protein composition between OMVs produced by untreated or treated bacteria, but no changes in membrane fluidity were detected among the OMV groups. Together, these results demonstrate that E-liquids modulate OMV biogenesis and composition in A. actinomycetemcomitans, potentially influencing its virulence and pathogenicity."

Journal • Cardiovascular • Dental Disorders • Periodontitis

Immunomodulatory effects of oral microbiota in the pathogenesis of rheumatoid arthritis. (PubMed, Front Immunol) - "Specific virulence factors, including the peptidylarginine deiminase from Porphyromonas gingivalis and leukotoxin A from Aggregatibacter actinomycetemcomitans, promote excessive protein citrullination and anti-citrullinated protein antibody generation, thereby contributing to the loss of immune tolerance, particularly in genetically susceptible individuals...In this review, we explored the potential mechanisms underlying the imbalance of the oral microbiota and its contribution to the onset and progression of RA, focusing on microbially induced citrullination, host genetic susceptibility, and common inflammatory pathways, while also discussing the impact of comprehensive periodontal management and lifestyle interventions on RA outcomes. Overall, these insights underscore the role of the oral microbiome in RA pathogenesis and suggest that addressing microbial dysbiosis through integrated therapeutic strategies may complement conventional care."

Journal • Review • Dental Disorders • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Arthritis • Periodontitis • Rheumatoid Arthritis • Rheumatology

Fimbriae potentiate Aggregatibacter actinomycetemcomitans for periodontal disease. (PubMed, Curr Res Microb Sci) - "The combined evidence implies that fimbriae and key virulence factors, such as leukotoxin A, act cooperatively in pathogenesis, as fimbriae-mediated adhesion and persistence will enhance local toxin delivery, killing of immune cells and immune evasion. Together, these insights point to fimbriae as key targets for novel therapeutic and vaccination strategies aimed at controlling periodontal and related systemic diseases."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dental Disorders • Immunology • Inflammatory Arthritis • Periodontitis • Rheumatoid Arthritis • Rheumatology

Chrysin and Luteolin from Moroccan Propolis to Prevent Aggressive Periodontitis Caused by Aggregatibacter actinomycetemcomitans Leukotoxin: A Computer-Aided Drug Design Approach. (PubMed, Pharmaceuticals (Basel)) - " These results highlight the potential of chrysin as a versatile inhibitor capable of interacting with the four active sites. These findings are a strong foundation for further experimental confirmations."

Journal • Dental Disorders • Infectious Disease • Periodontitis

Protective efficacy of the recombinantly expressed C-terminal domain of Mannheimia haemolytica leukotoxin in mice and goats. (PubMed, J Vet Res) - "A single administration of cLktA conferred 80% and 100% survival against a M. haemolytica challenge. These findings show the C-terminal region of Mannheimia haemolytica LktA to be a highly immunogenic and protective antigen and suggest its potential as a candidate for subunit vaccine development."

Journal • Preclinical • Respiratory Diseases

The Pathogenicity Mechanisms of Staphylococcus aureus. (PubMed, Int J Mol Sci) - "The activity of these regulatory systems is pivotal in determining whether S. aureus initiates an invasive infection, characterized by toxin and enzyme production (e.g., hemolysin alpha -Hla, phenol soluble modulins -PSM, toxic shock syndrome -TSST-1, enterotoxins, Panton-Valentine leukotoxin- PVL). This is indicative of community-acquired S. aureus (CA-Sa, CA-MRSA, CA-MSSA), or a chronic infection, characterized by surface protein expression and biofilm formation, which is indicative of hospital-acquired or healthcare-acquired S. aureus (HA-Sa, HA-MRSA, HA-MSSA)."

Journal • Review • Dermatology • Infectious Disease • Septic Shock

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