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Journal: Resistance profiling and molecular characterization of Staphylococcus aureus isolated from goats in Korea. (Pubmed Central) - Dec 15, 2020
However, all S. aureus isolates were sensitive to linezolid, rifampin, and vancomycin...In addition, ST72 MRSA-SCCmec IV isolates carried at least six staphylococcal leukotoxin- and enterotoxin-encoding genes (lukED, seg, sei, sem, sen, seo, and seq)...There is a possibility of transmission of MRSA from goat to human or contamination of food products. Therefore, regular microbiological investigation in goats, farms, and slaughterhouses is critical to determine the existence of virulent and multi-drug resistant (MDR) S. aureus and to implement preventive strategies.
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Journal: Recombinant protein subunit vaccine reduces puerperal metritis incidence and modulates the genital tract microbiome. (Pubmed Central) - Nov 26, 2020
The objective of this study was to evaluate the efficacy of 3 vaccine formulations containing proteins (FimH, leukotoxin, and pyolysin), inactivated whole cells (Escherichia coli, Fusobacterium necrophorum, and Trueperella pyogenes), or both, in the prevention of postpartum uterine diseases...In general, vaccination decreased the total vaginal bacterial load and decreased the vaginal load of F. necrophorum by 9 d in milk. Vaccination reduced the prevalence of puerperal metritis in the first lactation of dairy cows, leading to less metritic disease and improved reproduction.
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Journal: Cranberry Proanthocyanidins Neutralize the Effects of Aggregatibacter actinomycetemcomitans Leukotoxin. (Pubmed Central) - Nov 19, 2020
In summary, the present study showed that cranberry PACs reduced LtxA gene expression in A. actinomycetemcomitans and neutralized the cytolytic and pro-inflammatory responses of human macrophages treated with LtxA. Given these properties, cranberry PACs may represent promising molecules for prevention and treatment of the aggressive form of periodontitis caused by A. actinomycetemcomitans.
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Journal: Aggregatibacter actinomycetemcomitans leukotoxin: From mechanism to targeted anti-toxin therapeutics. (Pubmed Central) - Nov 12, 2020
Because of this correlation, much work over the past 30 years has been focused on understanding the mechanisms by which LtxA interacts with and kills host cells. In this article, we review those findings, highlight the remaining open questions, and demonstrate how knowledge of these mechanisms, particularly the toxin's interactions with lymphocyte function-associated antigen-1 (LFA-1) and cholesterol, enables the design of targeted anti-LtxA strategies to prevent/treat disease.
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Journal: Emergence of cfr-Mediated Linezolid Resistance in Staphylococcusaureus Isolated from Pig Carcasses. (Pubmed Central) - Nov 6, 2020
Staphylococcal enterotoxin and leukotoxin-encoding genes, alone or in combination, were detected in 68% of LR isolates...Collectively, toxigenic and LR S. aureus strains pose a crisis for public health. This study is the first to describe the mechanism of linezolid resistance in S. aureus isolated from food animal products in Korea.
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Journal: Effect of apo-lactoferrin on leukotoxin and outer membrane vesicles of Mannheimia haemolytica A2. (Pubmed Central) - Sep 24, 2020
In contrast, holo-BLf (with iron) did not have this effect, possibly due to differences in the tertiary structure between these proteins. In summary, apo-BLf affected the levels of several M. haemolytica virulence factors and could be evaluated for use in animals as an adjuvant in the treatment of ovine mannheimiosis.
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Review, Journal: Aggregatibacter actinomycetemcomitans (Aa) Under the Radar: Myths and Misunderstandings of Aa and Its Role in Aggressive Periodontitis. (Pubmed Central) - Sep 17, 2020
In this manner Aa can transfer to a protected but vulnerable domain (pocket or sulcus) where its community activism is most useful. Aa's "strategy" includes obtaining housing, food, and transportation at no cost to its partners challenging the economic theory that "there ain't no such thing as a free lunch." This "strategy" illustrates how co-evolution can promote Aa's survival, on one hand, and overgrowth of community members, on the other, which can result in local host dysbiosis and susceptibility to infection.
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Biomarker, Journal: Mechanisms by Which Small RNAs Affect Bacterial Activity. (Pubmed Central) - Jul 25, 2020
Furthermore, in clinical isolates, these associated RNAs could be explored not only as potential biomarkers for oral disease monitoring but also as alternative types of regulators for drug design. Thus, this emerging subspecialty of bacterial regulatory RNAs could reshape our understanding of bacterial gene regulation from their key roles of endogenous regulatory RNAs to their activities in pathologic processes.
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Journal: Unbiased identification of immunogenic Staphylococcus aureus leukotoxin B-cell epitopes. (Pubmed Central) - Jul 9, 2020
Thus, using a gene fragment, phage-display based pipeline, we have identified and validated immunogenic B-cell epitopes that are cross-reactive between members of the pore-forming leukocidin family. This approach could be harnessed to identify novel epitopes for a much needed Sa-protective subunit vaccine.
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Journal: Exposure to Aggregatibacter Actinomycetemcomitans before Symptom Onset and the Risk of Evolving to Rheumatoid Arthritis. (Pubmed Central) - Jun 28, 2020
IgM, IgG and IgA antibodies to Aa leukotoxin A (LtxA) were detected by ELISA in plasma from a cohort of Swedish adults at different stages of RA development, from before onset of symptoms to established disease...We found no association between anti-LtxA IgG/IgA antibodies and RA at any stage of disease development. The data support a temporal association between anti-LtxA IgM antibodies and the development of RA, suggesting that a subset of RA patients may have been exposed to Aa around the time of transition from being asymptomatic to become a patient with RA.
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Journal: Aggregatibacter actinomycetemcomitans leukotoxin causes activation of LFA-1. (Pubmed Central) - May 20, 2020
LtxA has a strong affinity for the cytosolic domains of both the α and β subunits (K = 15 nM and 4.2 nM, respectively) and a significantly lower affinity for the cytoplasmic domains of other integrin α , α and β subunits (K = 400, 180 and 230 nM, respectively), used as controls. Peptide fragments of α and β show that LtxA binds membrane-proximal domain of α , intermediate domain of β .
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Journal: Aggregatibacter actinomycetemcomitans colonization and persistence in a primate model. (Pubmed Central) - Apr 14, 2020
Variants in A. actinomycetemcomitans leukotoxin (ltx) were created, labeled, inoculated, and compared with their progenitor strain for in vivo colonization...Growth of attached A. actinomycetemcomitans in vivo was enhanced by lactate availability due to consorting species. These associations provide A. actinomycetemcomitans with the constituents required for its colonization and survival in the complex and competitive oral environment.
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Journal: Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB). (Pubmed Central) - Mar 18, 2020
Being central to its pathogenesis, S. aureus thwarts the host defense by secreting a myriad of virulence factors, including bicomponent, pore-forming leukotoxins...While the neutralization of LukAB alone was not sufficient to fully suppress leukotoxicity in supernatants of S. aureus USA300 isolates, a combination of antibodies against LukAB, α-toxin, and Panton-Valentine leukocidin completely neutralized the cytotoxicity of these strains. These data strongly support the inclusion of LukAB toxoids in a multivalent toxoid vaccine for the prevention of S. aureus disease.
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Journal: Rapid Purification of Endotoxin-Free RTX Toxins. (Pubmed Central) - Mar 18, 2020
Cytolytic leukotoxins of the repeat in toxin (RTX) family are large proteins excreted by gram-negative bacterial pathogens through the type 1 secretion system (T1SS)...Extensive on-column rinsing with 8 M urea buffer removes residual detergent and the eluted highly active RTX protein preparations then contain only trace amounts of LPS. The procedure is exemplified using four prototypic RTX cytolysins, the Bordetella pertussis CyaA and the hemolysins of Escherichia coli (HlyA), Kingella kingae (RtxA), and Actinobacillus pleuropneumoniae (ApxIA).
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Protein toxin sorting on the bacterial cell membrane (121C, Pennsylvania Convention Center) - Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_9552;
We have previously observed that the leukotoxin (LtxA) produced by Aggregatibacter actinomycetemcomitans associates with the surface of OMVs in a much higher concentration than on the OM...Our results demonstrate that the LPS structures in the two OMV populations is distinct. Together, these results demonstrate a mechanism by which a bacterial protein (toxin) is sorted to specific secreted vesicles due to variations in the toxin’s membrane affinity.
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Journal: Aggregatibacter actinomycetemcomitans LtxA Hijacks Endocytic Trafficking Pathways in Human Lymphocytes. (Pubmed Central) - Jan 26, 2020
Leukotoxin (LtxA), from oral pathogen Aggregatibacter actinomycetemcomitans, is a secreted membrane-damaging protein...Toxin trafficking via the degradative endocytic pathway may culminate in the delivery of the protein to lysosomes or its accumulation in Rab11A-dependent recycling endosomes. The ability of LtxA to form pores at acidic pH may result in permeabilization of the endosomal and lysosomal membranes.
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Journal: Virulence factors produced by Staphylococcus aureus biofilms have a moonlighting function contributing to biofilm integrity. (Pubmed Central) - Jan 23, 2020
Our analyses revealed the expression of many pathogenicity factors within S. aureus biofilms as indicated by a high abundance of capsule biosynthesis proteins along with various secreted virulence factors, including hemolysins, leukotoxins, and lipases as a part of the ECM...In consequence, this leads to strong cell aggregation and biofilm stabilization. Collectively, our study identified a new molecular mechanism during S. aureus biofilm formation and thus significantly widens the understanding of biofilm-associated S. aureus infections - an essential prerequisite for the development of novel antimicrobial therapies.
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Journal: Proteomic Analysis of Novel Components of Nemopilema nomurai Jellyfish Venom: Deciphering the Mode of Action. (Pubmed Central) - Jan 23, 2020
The identified toxins are phospholipase A2, phospholipase D Li Sic Tox beta IDI, a serine protease, putative Kunitz-type serine protease inhibitor, disintegrin and metalloproteinase, hemolysin, leukotoxin, three finger toxin MALT0044C, allergens, venom prothrombin activator trocarin D, tripeptide Gsp 9.1, and along with other toxin proteins...Here is the first report demonstrating the methodical overview of NnV proteomics research, providing significant information to understand the mechanism of NnV envenomation. Our proteomics findings can provide a platform for novel protein discovery and development of practical ways to deal with jellyfish stings on human beings.
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Journal: Periodontal sources of citrullinated antigens and TLR agonists related to RA. (Pubmed Central) - Oct 16, 2019
Frequently, the oral pathogens P. gingivalis and A. actinomycetemcomitans directly and indirectly participate in synovitis in RA, providing topical citrullination: P. gingivalis via PPAD and A. actinomycetemcomitans via leukotoxin A-mediated ROS-independent NET formation...However, the role of swallowed PD-derived sludge for the induction of oral tolerance remains to be established. We hypothesize (I) PD-driven endotoxemia may increase the host responsiveness to autoantigens via TLR4 activation and (II) this participates in development and propagation of RA (III) circulating PD-derived bacterial DNA is taken up by phagocytes, activates TLR9, and thus increases the responsiveness to autoantigens.
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Journal: Receptor-based Peptides for Inhibition of RTX Leukotoxin (LtxA) Activity. (Pubmed Central) - Sep 18, 2019
Further investigations into the mechanism by which these peptides inhibit LtxA binding to LFA-1 reveal a correlation between toxin-peptide affinity and LtxA-mediated cytotoxicity, leading to a diminished association between LtxA and LFA-1 on the cell membrane. Our results demonstrate the possibility of using target-based peptides to inhibit LtxA activity, and we expect that a similar approach could be used to hinder the activity of other RTX toxins.
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Journal: Mannheimia haemolytica in bovine respiratory disease: immunogens, potential immunogens, and vaccines. (Pubmed Central) - Sep 12, 2019
...Studies have focused on the capsule, lipopolysaccharide, various adhesins, extracellular enzymes, outer membrane proteins, and leukotoxin (LKT) resulting in a strong database for understanding immune responses to the bacterium and production of more efficacious vaccines...Studies of potential vaccines have led current commercial vaccines, which are composed primarily of culture supernatant, bacterin-toxoid, or live mutant bacteria. Several of those can be augmented experimentally by addition of recombinant LKT or outer membrane proteins.
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Journal: Proteomic analysis of the food spoiler Pseudomonas fluorescens ITEM 17298 reveals the antibiofilm activity of the pepsin-digested bovine lactoferrin. (Pubmed Central) - Sep 8, 2019
HLF caused a significant reduction in biofilm biomass; indeed, at 15 °C HLF repressed PleD, TycC and GbrS and induced the negative regulators of alginate biosynthesis; at both temperatures induced the cyclic-di-GMP-binding biofilm dispersal mediator (PROKKA_02061). In conclusion, in this work protein determinats of biofilm formation were revelead in ITEM 17298 under the low temperature; the synthesis of these latter were inhibited by HLF confirming its possible exploitation as antibiofilm agent for biotechnological applications in cold stored foods.
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Journal: A bovine CD18 signal peptide variant with increased binding activity to Mannheimia hemolytica leukotoxin. (Pubmed Central) - Sep 6, 2019
The results suggest that missense variants in the CD18 signal peptide affect Lkt binding, and animals carrying the C allele may be more susceptible to the effects of Lkt. The results also identify a potent class of non-antibiotic Lkt inhibitors that could potentially protect cattle from cytotoxic effects during acute lung infections.
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Journal: Catechin-Mediated Restructuring of a Bacterial Toxin Inhibits Activity. (Pubmed Central) - Aug 17, 2019
The results also identify a potent class of non-antibiotic Lkt inhibitors that could potentially protect cattle from cytotoxic effects during acute lung infections. Galloylated catechins modify protein toxin structure, inhibiting the toxin from binding to the requisite molecules on the host cell surface.
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Journal: Development of an aerosolized Mannheimia haemolytica experimental pneumonia model in clean-catch colostrum-deprived calves. (Pubmed Central) - Aug 9, 2019
...In an initial study, conventionally raised calves with higher levels of antibody against M. haemolytica leukotoxin developed acute respiratory distress and diffuse alveolar damage, but did not develop bronchopneumonia, following challenge with M. haemolytica serotype 1...Gross and histologic lesions included neutrophilic bronchopneumonia and fibrinous pleuritis, with oat cells (necrotic neutrophils with streaming nuclei), and areas of coagulative necrosis, which are similar to lesions in naturally occurring BRD. Thus, challenge with M. haemolytica serotype 1 and use of clean-catch colostrum-deprived calves with low or absent antibody titres allowed development of an effective aerosol challenge model that induced typical clinical disease and lesions.
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Journal: Leukotoxic activity of Fusobacterium necrophorum of cattle origin. (Pubmed Central) - Jul 26, 2019
...Among several virulence factors, leukotoxin (Lkt) is considered to be a major factor and a protective antigen...necrophorum strains appear to be much more variable. Use of BL3 cells in combination of lactic acid dehydrogenase assay appears to be a simple and valid assay to measure Lkt activity of F. necrophorum.
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Journal: Understanding the Virulence of Staphylococcus pseudintermedius: A Major Role of Pore-Forming Toxins. (Pubmed Central) - Jul 24, 2019
...In silico analysis found the presence of two PSMs (δ-toxin and PSMε) as well as Luk-I leukotoxin, the presence of which was confirmed by PCR in all clinical strains tested (n = 17)...The results suggest that the severity of S. pseudintermedius infections is, at least in part, explained by a combined action of Luk-I that specifically targets immune cells expressing the CXCR2 receptor, and PSMs that disrupt cell membranes whatever the cell types. The present study strengthens the key role of PSMs in virulence of the different species belonging to Staphylococcus genus.
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Journal, IO Biomarker: A Critical Role for HlgA in Staphylococcus aureus Pathogenesis Revealed by A Switch in the SaeRS Two-Component Regulatory System. (Pubmed Central) - Jul 19, 2019
Cytolytic pore-forming toxins including alpha hemolysin (Hla) and bicomponent leukotoxins play an important role in the pathogenesis of Staphylococcus aureus...The culture supernatant from Newman S. aureus could be neutralized by antisera against two vaccine candidates based on LukS and LukF subunits of Panton-Valentine leukocidin but not by an anti-Hla neutralizing antibody. These findings display the complex involvement of Sae and Agr systems in regulating the virulence of S. aureus and have important implications for vaccine and immunotherapeutics development for S. aureus disease in humans.
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