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PeerJ 2024The respiratory pathogen nontypeable (NTHi) is the most common cause of exacerbation of chronic obstructive pulmonary disease (COPD), of which an excessive inflammatory...
The respiratory pathogen nontypeable (NTHi) is the most common cause of exacerbation of chronic obstructive pulmonary disease (COPD), of which an excessive inflammatory response is a hallmark. With the limited success of current medicines there is an urgent need for the development of novel therapeutics that are both safe and effective. In this study, we explored the regulatory potential of pomegranate-derived peptides Pug-1, Pug-2, Pug-3, and Pug-4 on NTHi-induced inflammation. Our results clearly showed that to varying degrees the Pug peptides inhibited NTHi-induced production of IL-1, a pivotal cytokine in COPD, and showed that these effects were not related to cytotoxicity. Pug-4 peptide exhibited the most potent inhibitory activity. This was demonstrated in all studied cell types including murine (RAW264.7) and human (differentiated THP-1) macrophages as well as human lung epithelial cells (A549). Substantial reduction by Pug-4 of TNF-, NO and PGE in NTHi-infected A549 cells was also observed. In addition, Pug-4 strongly inhibited the expression of nuclear-NF-B p65 protein and the NF-B target genes (determined by IL-1, TNF-, iNOS and COX-2 mRNA expression) in NTHi-infected A549 cells. Pug-4 suppressed the expression of NLRP3 and pro-IL-1 proteins and inhibited NTHi-mediated cleavage of caspase-1 and mature IL-1. These results demonstrated that Pug-4 inhibited NTHi-induced inflammation through the NF-B signaling and NLRP3 inflammasome activation. Our findings herein highlight the significant anti-inflammatory activity of Pug-4, a newly identified peptide from pomegranate, against NTHi-induced inflammation. We therefore strongly suggest the potential of the Pug-4 peptide as an anti-inflammatory medicine candidate for treatment of NTHi-mediated inflammation.
Topics: Animals; Humans; Mice; Anti-Inflammatory Agents; Haemophilus influenzae; Inflammasomes; Inflammation; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Pomegranate; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha; Phytochemicals
PubMed: 38406294
DOI: 10.7717/peerj.16938 -
Frontiers in Cellular and Infection... 2024The association between periodontitis (PD) and Parkinson's disease (PK) is discussed due to the inflammatory component of neurodegenerative processes. PK severity and...
UNLABELLED
The association between periodontitis (PD) and Parkinson's disease (PK) is discussed due to the inflammatory component of neurodegenerative processes. PK severity and affected areas were determined using the following neuropsychological tests: Unified Parkinson's Disease Rating Score (UPDRS) and Hoehn and Yahr; non-motoric symptoms by Non-Motor Symptoms Scale (NMSS), and cognitive involvement by Mini-Mental State Examination (MMSE). Neuroinflammation and the resulting Glucose-6-Phosphatase-Dehydrogenase (G6PD) dysfunction are part of the pathophysiology of PK. This study aimed to evaluate these associations in periodontal inflammation. Clinical data and saliva-, serum-, and RNA-biobank samples of 50 well-characterized diametric patients with PK and five age- and sex-matched neurologically healthy participants were analyzed for G6PD function, periodontal pathogens (, and , monocyte chemoattractant protein (MCP) 1, and interleukin (IL) 1-beta. Regression analysis was used to identify associations between clinical and behavioral data, and t-tests were used to compare health and disease. Compared with PK, no pathogens and lower inflammatory markers (p < 0.001) were detectible in healthy saliva and serum, PK-severity/UPDRS interrelated with the occurrence of in serum as well as IL1-beta levels in serum and saliva (p = 0.006, 0.019, 0.034), Hoehn and Yahr correlated with , , RNA IL1-beta regulation, serum, and saliva IL1-beta levels, with p-values of 0.038, 0.011, 0.008, <0.001, and 0.010, while MMSE was associated with , , serum MCP 1 levels, RNA IL1-beta regulation and G6PD serum activity (p = 0.036, 0.003, 0.045, <0.001, and 0.021). Cognitive and motor skills seem to be important as representative tests are associated with periodontal pathogens and oral/general inflammation, wherein G6PD-saliva dysfunction might be involved.
CLINICAL TRIAL REGISTRATION
https://www.bfarm.de/DE/Das-BfArM/Aufgaben/Deutsches-Register-Klinischer-Studien/_node.html, identifier DRKS00005388.
Topics: Humans; Aggregatibacter actinomycetemcomitans; Fusobacterium nucleatum; Inflammation; Parkinson Disease; Periodontitis; Porphyromonas gingivalis; Prevotella intermedia; RNA; Glucosephosphate Dehydrogenase
PubMed: 38404290
DOI: 10.3389/fcimb.2024.1298546 -
BMC Veterinary Research Feb 2024Sheep and goat production in Ethiopia is hindered by numerous substandard production systems and various diseases. Respiratory disease complexes (RDC) pose a significant...
BACKGROUND
Sheep and goat production in Ethiopia is hindered by numerous substandard production systems and various diseases. Respiratory disease complexes (RDC) pose a significant threat to the productivity of these animals. Pneumonia is a common manifestation of respiratory disease complexes and often necessitates a prolonged course of antibiotic treatment. This study aimed to optimize and propose the ideal duration of therapy for pneumonia in sheep and goats.
METHODS
The study was conducted from February to June 2021 at the Veterinary Teaching Hospital of the College of Veterinary Medicine and Agriculture, Addis Ababa University. The study recruited 54 sheep and goats presented to the hospital for treatment with a confirmed RDC as determined based on clinical signs and bacteriological methods. The animals were randomly allocated to 5 groups each group receiving 10% oxytetracycline (Phenxyl, Phenix, Belgum) intramuscularly for a duration of 3, 4, 5, 6 and 7 consecutive days. The treatment outcomes were assessed by recording vital signs (body temperature, respiratory rate, heart rate, coughing, and nasal discharges), performing lung ultrasonography (L-USG) as well as collection of nasal swabs for bacterial isolation and molecular identification before and after completion of the treatment. An ordered logistic regression model with random effects was employed to determine the optimal therapeutic duration, taking into account the cumulative scores of the outcome variables across the different groups.
RESULTS
Among the 54 sheep and goats treated with 10% oxytetracycline, a total of 74.07% (95% CI, 60.35-85.04) achieved complete recovery, as confirmed through clinical, ultrasound, and bacteriological methods. In Group 1 (G1), out of 12 sheep and goats, 8 (83.0%) recovered completely; in Group 2 (G2), out of 11 animals, 9 (82.0%) recovered completely; in Group 3 (G3), out of 11 animals, 10 (93.0%) recovered completely; in Group 4 (G4), out of 9 animals, 9 (100.0%) recovered completely; and in Group 5 (G5), out of 11 animals, 10 (91.0%) recovered completely. Bacteriological examination of nasal swabs indicated involvement of M. hemolytica in 27 (50.00%) and P. multocida in 13 (24.07%) of pneumonic animals. Detection of specific marker genes confirmed only five of the presumptive M. hemolytica isolates, whilst no isolates tested positive for P. multocida. Post-treatment samples collected from recovered animals did not yield any M. hemolytica nor P. multocida. Based on results from clinical signs, L-USG, and bacterial infection variables, the group of sheep and goats treated for seven consecutive days (G5) showed the highest recovery score compared to the other groups, and there was a statistically significant difference (coefficient (β) = - 2.296, p = 0.021) in variable score between G5 and G1. These findings suggest that the administration of 10% oxytetracycline for a full course of seven consecutive days resulted in symptomatic and clinical recovery rates from respiratory disease in sheep and goats.
Topics: Animals; Ethiopia; Goat Diseases; Goats; Hospitals, Animal; Hospitals, Teaching; Oxytetracycline; Pasteurella multocida; Pneumonia, Bacterial; Sheep; Sheep Diseases
PubMed: 38395815
DOI: 10.1186/s12917-024-03917-z -
Pathogens (Basel, Switzerland) Jan 2024Infective endocarditis (IE), a disease of the endocardial surface of the heart, is usually of bacterial origin and disproportionally affects individuals with underlying... (Review)
Review
Infective endocarditis (IE), a disease of the endocardial surface of the heart, is usually of bacterial origin and disproportionally affects individuals with underlying structural heart disease. Although IE is typically associated with Gram-positive bacteria, a minority of cases are caused by a group of Gram-negative species referred to as the HACEK group. These species, classically associated with the oral cavity, consist of bacteria from the genera (excluding ), , , , and . , a bacterium of the Pasteurellaceae family, is classically associated with Aggressive Periodontitis and is also concomitant with the chronic form of the disease. Bacterial colonization of the oral cavity serves as a reservoir for infection at distal body sites via hematological spreading. adheres to and causes disease at multiple physiologic niches using a diverse array of bacterial cell surface structures, which include both fimbrial and nonfimbrial adhesins. The nonfimbrial adhesin EmaA (extracellular matrix binding protein adhesin A), which displays sequence heterogeneity dependent on the serotype of the bacterium, has been identified as a virulence determinant in the initiation of IE. In this chapter, we will discuss the known biochemical, molecular, and structural aspects of this protein, including its interactions with extracellular matrix components and how this multifunctional adhesin may contribute to the pathogenicity of A. actinomycetemcomitans.
PubMed: 38392837
DOI: 10.3390/pathogens13020099 -
Journal of Bacteriology Mar 2024is an important respiratory pathogen that can cause porcine contagious pleuropneumonia (PCP), resulting in significant economic losses in swine industry. Microorganisms...
is an important respiratory pathogen that can cause porcine contagious pleuropneumonia (PCP), resulting in significant economic losses in swine industry. Microorganisms are subjected to drastic changes in environmental osmolarity. In order to alleviate the drastic rise or fall of osmolarity, cells activate mechanosensitive channels MscL and MscS through tension changes. MscL not only regulates osmotic pressure but also has been reported to secrete protein and uptake aminoglycoside antibiotic. However, MscL and MscS, as the most common mechanosensitive channels, have not been characterized in . In this study, the osmotic shock assay showed that MscL increased sodium adaptation by regulating cell length. The results of MIC showed that deletion of decreased the sensitivity of to multiple antibiotics, while deletion of rendered hypersensitive to penicillin. Biofilm assay demonstrated that MscL contributed the biofilm formation but MscS did not. The results of animal assay showed that MscL and MscS did not affect virulence . In conclusion, MscL is essential for sodium hyperosmotic tolerance, biofilm formation, and resistance to chloramphenicol, erythromycin, penicillin, and oxacillin. On the other hand, MscS is only involved in oxacillin resistance.IMPORTANCEBacterial resistance to the external environment is a critical function that ensures the normal growth of bacteria. MscL and MscS play crucial roles in responding to changes in both external and internal environments. However, the function of MscL and MscS in has not yet been reported. Our study shows that MscL plays a significant role in osmotic adaptation, antibiotic resistance, and biofilm formation of , while MscS only plays a role in antibiotic resistance. Our findings provide new insights into the functional characteristics of MscL and MscS in . MscL and MscS play a role in antibiotic resistance and contribute to the development of antibiotics for .
Topics: Animals; Swine; Actinobacillus pleuropneumoniae; Anti-Bacterial Agents; Virulence; Oxacillin; Sodium; Swine Diseases
PubMed: 38391161
DOI: 10.1128/jb.00429-23 -
Alcohol (Fayetteville, N.Y.) Feb 2024Alcohol consumption is not uncommon among people with HIV (PWH) and may exacerbate HIV-induced intestinal damage, and further lead to dysbiosis and increased intestinal...
OBJECTIVES
Alcohol consumption is not uncommon among people with HIV (PWH) and may exacerbate HIV-induced intestinal damage, and further lead to dysbiosis and increased intestinal permeability. This study aimed to determine the changes in the faecal microbiota and its association with alcohol consumption in HIV-infected patients.
METHODS
A cross-sectional survey was conducted between November 2021 and May 2022, and 93 participants were recruited. To investigate the alterations of alcohol misuse on fecal microbiology in HIV-infected individuals, we performed 16s rDNA gene sequencing on fecal samples from the low to moderate drinking (n=21) and non-drinking (n=72) groups.
RESULTS
Comparison between groups using alpha and beta diversity showed that the diversity of stool microbiota in the low to moderate drinkinge group did not differ from that of the non-drinking group (all P>0.05). The Linear discriminant Analysis effect size (LEfSe) algorithm was to determine the bacterial taxa associated with alcohol consumption, and the results showed altered fecal bacterial composition in HIV-infected patients who consumed alcohol, with Coprobacillus, Pseudobutyrivibrio and Peptostreptococcaceae enriched, and Pasteurellaceae and Xanthomonadaceae were depleted. In addition, by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional microbiome features were also found to be altered in the low to moderate drinking group, showing a reduction in metabolic pathways (P=0.036) and cardiovascular disease pathway (P=0.006).
CONCLUSION
Low to moderate drinking will change the composition, metabolism and cardiovascular disease pathway of the gut microbiota of HIV-infected patients.
PubMed: 38387693
DOI: 10.1016/j.alcohol.2024.02.003 -
Microbiology Spectrum Apr 2024serogroup F can infect a number of animals. However, the pathogenicity and genomic features of this serogroup are still largely unknown. In the present study, the...
UNLABELLED
serogroup F can infect a number of animals. However, the pathogenicity and genomic features of this serogroup are still largely unknown. In the present study, the pathogenicity and genomic sequences of 19 rabbit-sourced serogroup F isolates were determined. The 19 isolates were highly pathogenic for rabbits causing severe pathologic lesions and high mortality in inoculated rabbits. Nevertheless, the pathologic lesions in rabbits caused by the 19 isolates were distinct from those caused by the previously reported high-virulent serogroup F strains J-4103 (rabbit), P-4218 (turkey), and C21724H3km7 (chicken). Moreover, the 19 isolates were avirulent to white feather broilers. The genomes of the 19 isolates were determined to understand the pathogenicity of these isolates. The finding of a number of functional genes in the 19 isolates by comparison with the low-virulent rabbit-sourced serogroup F strain s4 might contribute to the high virulence of these isolates. Notably, polymorphisms were determined in the lipopolysaccharide outer core biosynthetic genes and among the serogroup F strains of different hosts. However, the sequences of and from rabbit-sourced strains (except for SD11) were identical, which might be responsible for the host specific of the 19 isolates. The observations and findings in this study would be helpful for the understanding of the pathogenicity variation and host predilection of .
IMPORTANCE
The 19 rabbit-sourced serogroup F isolates showing high virulence to rabbits were avirulent to the broilers. Notably, polymorphisms were determined in the lipopolysaccharide outer core biosynthetic genes and among all serogroup F strains of different hosts. However, the sequences of and from rabbit-sourced strains (except for SD11) were identical, which might be responsible for the host specific of the 19 isolates.
Topics: Animals; Rabbits; Pasteurella multocida; Pasteurella Infections; Serogroup; Chickens; Lipopolysaccharides; Genomics
PubMed: 38385714
DOI: 10.1128/spectrum.03654-23 -
MSphere Mar 2024Iron acquisition is a key feature dictating the success of pathogen colonization and infection. Pathogens scavenging iron from the host must contend with other members...
UNLABELLED
Iron acquisition is a key feature dictating the success of pathogen colonization and infection. Pathogens scavenging iron from the host must contend with other members of the microbiome similarly competing for the limited pool of bioavailable iron, often in the form of heme. In this study, we identify a beneficial role for the heme-binding protein hemophilin (Hpl) produced by the non-pathogenic bacterium against its close relative, the opportunistic respiratory tract pathogen non-typeable (NTHi). Using a mouse model, we found that pre-exposure to significantly reduced NTHi colonization of the upper airway and impaired NTHi infection of the lungs in an Hpl-dependent manner. Further, treatment with recombinant Hpl was sufficient to decrease airway burdens of NTHi without exacerbating lung immunopathology or systemic inflammation. Instead, mucosal production of the neutrophil chemokine CXCL2, lung myeloperoxidase, and serum pro-inflammatory cytokines IL-6 and TNFα were lower in Hpl-treated mice. Mechanistically, suppressed NTHi growth and adherence to human respiratory tract epithelial cells through the expression of Hpl, and recombinant Hpl could recapitulate these effects. Together, these findings indicate that heme sequestration by non-pathogenic, Hpl-producing is protective against NTHi colonization and infection.
IMPORTANCE
The microbiome provides a critical layer of protection against infection with bacterial pathogens. This protection is accomplished through a variety of mechanisms, including interference with pathogen growth and adherence to host cells. In terms of immune defense, another way to prevent pathogens from establishing infections is by limiting the availability of nutrients, referred to as nutritional immunity. Restricting pathogen access to iron is a central component of this approach. Here, we uncovered an example where these two strategies intersect to impede infection with the respiratory tract bacterial pathogen . Specifically, we find that a non-pathogenic (commensal) bacterium closely related to called improves protection against by limiting the ability of this pathogen to access iron. These findings suggest that beneficial members of the microbiome improve protection against pathogen infection by effectively contributing to host nutritional immunity.
Topics: Humans; Haemophilus influenzae; Heme; Haemophilus Infections; Lung; Iron; Haemophilus
PubMed: 38380941
DOI: 10.1128/msphere.00006-24 -
The Journal of Antimicrobial... Apr 2024The emergence of macrolide and tetracycline resistance within Pasteurella multocida isolated from feedlot cattle and the dominance of ST394 in Australia was reported...
BACKGROUND
The emergence of macrolide and tetracycline resistance within Pasteurella multocida isolated from feedlot cattle and the dominance of ST394 in Australia was reported recently.
OBJECTIVES
To establish the genetic context of the resistance genes in P. multocida 17BRD-035, the ST394 reference genome, and conduct a molecular risk assessment of their ability to disperse laterally.
METHODS
A bioinformatic analysis of the P. multocida 17BRD-035 genome was conducted to determine if integrative conjugative elements (ICEs) carrying resistance genes, which hamper antibiotic treatment options locally, are in circulation in Australian feedlots.
RESULTS
A novel element, ICE-PmuST394, was characterized in P. multocida 17BRD-035. It was also identified in three other isolates (two ST394s and a ST125) in Australia and is likely present in a genome representing P. multocida ST79 from the USA. ICE-PmuST394 houses a resistance module carrying two variants of the blaROB gene, blaROB-1 and blaROB-13, and the macrolide esterase gene, estT. The resistance gene combination on ICE-PmuST394 confers resistance to ampicillin and tilmicosin, but not to tulathromycin and tildipirosin. Our analysis suggests that ICE-PmuST394 is circulating both by clonal expansion and horizontal transfer but is currently restricted to a single feedlot in Australia.
CONCLUSIONS
ICE-PmuST394 carries a limited number of unusual antimicrobial resistance genes but has hotspots that facilitate genomic recombination. The element is therefore amenable to hosting more resistance genes, and therefore its presence (or dispersal) should be regularly monitored. The element has a unique molecular marker, which could be exploited for genomic surveillance purposes locally and globally.
Topics: Animals; Cattle; Pasteurella multocida; Australia; Anti-Bacterial Agents; Macrolides
PubMed: 38380682
DOI: 10.1093/jac/dkae040 -
Virulence Dec 2024(APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that -producing...
(APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that -producing bovine neutrophil β-defensin-5 (B5) could resist the infection by the bovine intracellular pathogen . In this study, the roles of synthetic B5 in regulating mucosal innate immune response and protecting against extracellular APP infection were further investigated using a mouse model. Results showed that B5 promoted the production of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-β in macrophages as well as dendritic cells (DC) and enhanced DC maturation . Importantly, intranasal B5 was safe and conferred effective protection against APP via reducing the bacterial load in lungs and alleviating pulmonary inflammatory damage. Furthermore, in the early stage of APP infection, we found that intranasal B5 up-regulated the secretion of TNF-α, IL-1β, IL-17, and IL-22; enhanced the rapid recruitment of macrophages, neutrophils, and DC; and facilitated the generation of group 3 innate lymphoid cells in lungs. In addition, B5 activated signalling pathways associated with cellular response to IFN-β and activation of innate immune response in APP-challenged lungs. Collectively, B5 via the intranasal route can effectively ameliorate the immune suppression caused by early APP infection and provide protection against APP. The immunization strategy may be applied to animals or human respiratory bacterial infectious diseases. Our findings highlight the potential importance of B5, enhancing mucosal defence against intracellular bacteria like APP which causes early-phase immune suppression.
Topics: Humans; Swine; Animals; Cattle; Immunity, Innate; Actinobacillus pleuropneumoniae; Lymphocytes; Lung; Tumor Necrosis Factor-alpha; Immunosuppression Therapy
PubMed: 38378464
DOI: 10.1080/21505594.2024.2316459