Virulence Components Research Articles

The assessment of several extraction methods, purification, and characterization of Pseudomonas aeruginosa lipopolysaccharide (LPS) and studying its biological activity

Many Gram-negative bacteria have LPS, a virulent component, on their outer membranes. LPS, a surface structural component protects the outside layer while intoxicating host cells. Research linked LPS to antibiotic tolerance and biofilm formation. LPS induces pathophysiological effects, LPS is pyrogenic, it causes endotoxin shock and induces the clinical manifestations of infections. Therefore, several methods for isolating and purifying LPS have been developed. Extraction, purification, characterization and yields of Lipopolysaccharide (LPS) were obtained from P. aeruginosa through various methods to determine the pyrogenic effect of extracted LPS (ELPS) in rabbits. The study included the extraction of LPS from P. aeruginosa using manual methods including the modified hot (phenol-water) method, the methanol/ chloroform extraction method and an LPS extraction kit. The extracted LPS was detected and characterized by SDS-PAGE with silver staining and purified with HPLC. The protein and nucleic acid content of Extracted LPS were detected using SDS-PAGE with Coomassie blue staining and gel electrophoresis respectively. The study also determined the pyrogenic effect of extracted LPS (ELPS) in rabbits. Extracted LPS, demonstrated a typical ladder pattern upon silver staining and no contaminating protein was observed by coomassie blue staining and contamination of nucleic acid. In contrast, the extracted LPS without the enzymatic treatments revealed lighter protein and nucleic acid contamination bands. The elevated body temperature of rabbits following intraperitoneal administration of purified LPSs confirmed the functional activity of extracted LPSs. It was concluded from the study that the LPS extracted with manual methods and with an extraction kit showed high purity and yield compared to standard LPS. The modified hot (phenol-water) method showed the highest yield among all three methods. Rabbit pyrogencity testing of extracted LPS demonstrated the endotoxin's biological activity and pyrogenic nature.

Helicobacter pylori CagA mediated mitophagy to attenuate the NLRP3 inflammasome activation and enhance the survival of infected cells

Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease.

Xanthone Inhibitors of Unfolded Protein Response Isolated from Calophyllum caledonicum.

The unfolded protein response (UPR) is a key component of fungal virulence. The prenylated xanthone γ-mangostin isolated from Garcinia mangostana (Clusiaceae) fruit pericarp, has recently been described to inhibit this fungal adaptative pathway. Considering that Calophyllum caledonicum (Calophyllaceae) is known for its high prenylated xanthone content, its stem bark extract was fractionated using a bioassay-guided procedure based on the cell-based anti-UPR assay. Four previously undescribed xanthone derivatives were isolated, caledonixanthones N-Q (3, 4, 8, and 12), among which compounds 3 and 8 showed promising anti-UPR activities with IC50 values of 11.7 ± 0.9 and 7.9 ± 0.3 μM, respectively.

Cryo-EM structure of Influenza A virus NS1 and antiviral protein kinase PKR complex

Influenza A virus is the cause of a widespread human disease with high morbidity and mortality rates. The influenza virus encodes non-structural protein 1 (NS1), an exceedingly multifunctional virulence component. NS1 plays essential roles in viral replication and evasion of the cellular innate immune system. Protein kinase RNA-activated also known as protein kinase R (PKR) phosphorylates translation initiation factor eIF-2α on serine 51 to inhibit protein synthesis in virus-infected mammalian cells. Consequently, PKR activation inhibits mRNA translation, which results in the assert of both viral protein synthesis and cellular and possibly apoptosis in response to virus infection. Host signaling pathways are important in the replication of influenza virus, but the mechanisms involved remain to be characterized. Herein, the structure of NS1 and PKR complex was determined using Cryo-EM. We found the N91, E94, and G95 residues of PKR bind directly with N188, D125, and K126, respectively, of NS1. Furthermore, the study shows that PKR peptide offers a potential treatment for Influenza A virus infections.

A colorimetric and SERS dual-mode aptasensor for the detection of Shiga toxin type II based on Mn/Fe-MIL(53)@AuNSs

Shiga toxin type II (Stx2), the major virulence component of enterohemorrhagic Escherichia coli, is strongly associated with the life-threatening hemolytic uremic syndrome thus posing a substantial risk to food safety and human health. In this work, a dual-mode aptasensor with colorimetric and surface-enhanced Raman scattering was developed for Stx2 specific detection based on noble metal nanoparticles and Raman reporter loaded metal-organic framework (Mn/Fe-MIL(53)@AuNSs-MBA). The Mn/Fe-MIL(53)@AuNSs could catalyze the H2O2-mediated oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB), thereby enabling visual detection. Meanwhile, the SERS signal from MBA can be enhanced by the decorated AuNSs. Under optimal conditions, a linear range of 0.05–500 ng/mL with limit of detection (LOD) of 26 pg/mL was achieved in colorimetric mode and a linear range of 5–1000 ng/mL with LOD of 0.82 ng/mL in SERS mode, in which the dual-mode results complement each other, widening the linear range, increasing the accuracy and reliability of the detection. The method was further applied to the detection of Stx2 in milk with average recovery of 101.1 %, demonstrating its superior potential for bacterial toxin monitoring.

Molecular Characteristics of Virulence Genes in Carbapenem-Resistant and Carbapenem-Sensitive Klebsiella Pneumoniae in Relation to Different Capsule Serotypes in Ningbo, China.

Klebsiella pneumoniae (KP) is a common nosocomial pathogen. Capsules are an important component of KP's virulence, among which the K1, K2, K5, K20, K54, and K57 serotypes are predominant and exhibit varying degrees of virulence. The capsule and virulence genes of 150 carbapenem-resistant Klebsiella pneumoniae (CRKP) and 213 carbapenem-sensitive Klebsiella pneumoniae (CSKP) isolates were examined by polymerase chain reaction (PCR). The isolates were tested for hypermucoviscosity by string tests. Phylogenetic relationships between KP isolates were analyzed using multilocus sequence typing (MLST) and a Galleria mellonella infection model confirmed the differences in virulence. A total of 111 of 363 isolates of KP were detected, the highest detected serotypes were K1, K5, and K2, and CSKP was detected more frequently than CRKP. There was a greater prevalence of K1 and K2 serotypes in CSKP, while in CRKP, K5 serotypes were more prevalent. K1 isolates had the highest detection rates for hypermucoviscosity Klebsiella pneumoniae (hmKP) and hypervirulent Klebsiella pneumoniae (hvKP), and carried the most virulence genes. K54 isolates had the lowest detection rate of hmKP while K5 isolates had the lowest detection rate of hvKP and carried the fewest virulence genes. MLST results for serotypes K1, K20, and K57 showed significant homogeneity, while those for serotypes K2, K5, and K54 showed diversity. The Galleria mellonella infection model showed that the K1 serotype was the most virulent and the K54 serotype was the weakest. CSKP isolates were detected more frequently than CRKP isolates for capsular serotype detection. K1 isolates had the most virulence gene and strongest virulence, K5 isolates carried the fewest virulence genes, and K54 isolates had the weakest virulence. Furthermore, significant homogeneity was observed among K1, K20, and K57 isolates.

Surface modification of medical grade biomaterials by using a low-temperature-processed dual functional Ag-TiO2 coating for preventing biofilm formation.

Biofilm development in medical devices is considered the major virulence component that leads to increased mortality and morbidity among patients. Removing a biofilm once formed is challenging and frequently results in persistent infections. Many current antibiofilm coating strategies involve harsh conditions causing damage to the surface of the medical devices. To address the issue of bacterial attachment in medical devices, we propose a novel antibacterial surface modification approach. In this paper, we developed a novel low-temperature based solution-processed approach to deposit silver nanoparticles (Ag NPs) inside a titanium oxide (TiO2) matrix to obtain a Ag-TiO2 nanoparticle coating. The low temperature (120 °C)-based UV annealed drop cast method is novel and ensures no surface damage to the medical devices. Various medical-grade biomaterials were then coated using Ag-TiO2 to modify the surface of the materials. Several studies were performed to observe the antibacterial and antibiofilm properties of Ag-TiO2-coated medical devices and biomaterials. Moreover, the Ag-TiO2 NPs did not show any skin irritation in rats and showed biocompatibility in the chicken egg model. This study indicates that Ag-TiO2 coating has promising potential for healthcare applications to combat microbial infection and biofilm formation.

Occidiofungin inhibition of Candida biofilm formation on silicone elastomer surface.

Biofilms are the leading cause of clinically acquired fungal infections and contribute to significantly high morbidity and mortality in immunocompromised and hospitalized patients. Candida biofilms exhibit increased resistance to currently available antifungal agents that contribute to persistent reoccurring infections and are driving efforts to identify novel fungicidal compounds. The natural product, occidiofungin, is an antifungal compound with demonstrated activity against hyphal morphogenesis in polymorphic Candida species. In this study, we use an in vitro static biofilm model to demonstrate the efficacy of occidiofungin against C. albicans and C. tropicalis at all stages of biofilm development, including inhibiting cell dispersal. Consistent with prior findings, we demonstrate that actin organization is altered following occidiofungin exposure to include loss of F-actin cables and accumulation of actin aggregates. Altogether, our results provide strong evidence of the antibiofilm activity of occidiofungin toward Candida biofilms and support its potential as a therapeutic for Candida infections. IMPORTANCE Candida are opportunistic fungal pathogens with medical relevance given their association with superficial to life-threatening infections. An important component of Candida virulence is the ability to form a biofilm. These structures are highly resistant to antifungal therapies and are often the cause of treatment failure. In this work, we evaluated the efficacy of the antifungal compound, occidiofungin, against Candida biofilms developed on a silicone surface. We demonstrate that occidiofungin eliminated cells at all stages of biofilm formation in a dose-dependent manner. Consistent with our understanding of occidiofungin bioactivity, we noted alterations to actin organization and cell morphology following antifungal exposure. Given the challenges associated with the treatment of biofilm-associated infections, occidiofungin exhibits potential as a therapeutic antifungal agent in the future.

Molecular docking and molecular dynamics studies of natural products unravel potential inhibitors against OmpA of Acinetobacter baumannii

Emerging antimicrobial resistance has highlighted the need to design more effective antibiotics to treat deadly bacterial infections. Acinetobacter baumannii’s outer membrane protein A (OmpA) is a critical virulence component involved in biofilm formation, immunomodulation, and antibiotic resistance, which characterizes it as a potential therapeutic target. The present study aimed to screen the natural product database (>1,00,000) to identify the potential inhibitor against OmpA. Molecular docking studies revealed that 10 compounds had good docking scores (≤ −7 kcal/mol) compared to the reported inhibitor epiestriol (-3.079). Further, these 10 compounds were subjected to ADME analysis and MMGBSA analysis. Based on MMGBSA results, we selected 5 compounds [NP-1 (MolPort-039-337-117), NP-5(MolPort-019-932-973), NP-6 (MolPort-005-948-336), NP-8(MolPort-042-673-978) and NP-9(MolPort-042-673-766)] with high binding affinity. Molecular dynamics simulation found that NP-5, NP-8, and NP-9 were stable after analysing their RMSD, RMSF, the radius of gyration, and hydrogen interactions of complexes. Our study revealed that NP-5, NP-8, and NP-9 bind perfectly with OmpA and can act as its potential inhibitors. The results of this study imply that the identified inhibitors have the potential for further investigation. Communicated by Ramaswamy H. Sarma

In vitro effects of deferoxamine on antibiotic susceptibility in Gram-negative bacteria.

Iron is a vital element for the growth of bacteria. Bacteria use several strategies to scavenge iron, such as siderophores, which are thought to be important virulence components. The mammalian host uses various iron-binding substances to make iron unavailable for bacterial uptake. Deferoxamine (DFO) is a semi-synthetic iron chelator that has been licensed for medical use. Iron chelators like DFO may provide an alternative therapeutic technique for treating Gram-negative bacteria infections, which frequently display multidrug resistance. We assumed that iron deprivation or interactions with the cell membrane caused by DFO or increased siderophore synthesis may cause the inhibition or inactivation of proteins and enzymes necessary for critical processes in bacteria. Additionally, we proposed that these bacterial alterations might be the origin of synergistic interactions between DFO and several antibiotics. To test this hypothesis, we used disc diffusion, broth microdilution and checkerboard synergy testing methods on combinations of DFO with ceftriaxone, cefepime, meropenem, amikacin, levofloxacin, and tigecycline, respectively, in a total of 55 isolates (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Proteus mirabilis strains - 11 isolates for each genus). No synergistic or antagonistic interactions were observed between DFO and the tested antibiotics in the E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii isolates, while the addition of DFO significantly increased the inhibition zone diameters of cefepime, amikacin, meropenem, tigecycline, and levofloxacin in P. mirabilis isolates. According to the checkerboard synergy results, a synergistic interaction was found between DFO and tigecycline, cefepime and amikacin for P. mirabilis isolates. Among the investigated bacteria, a synergy between antibiotics and DFO was only discovered against P. mirabilis. We do not believe that this entirely disproves our hypothesis, though. The production of siderophores triggered by the increased metabolic activity of actively proliferating bacteria at the infection site may provide better results. Therefore, expanding these investigations and developing infection models through animal testing would be advantageous.

Discernment of Acinetobacter Species in World Scenario

The morphology of Acinetobacter species is Gram-negative, nonmotile, nonfermenting, Strictly aerobic, Oxidase negative, and Catalase positive. It usually results from an infectious agent and is nonpathogenic in healthy people. A. baumannii can survive, for a long time and spread quickly in a hospital setting. Acinetobacter baumannii can cause many infections, the most common of which are bloodstream infections and nosocomial pneumonia in severe patients. These infections have a high mortality rate & the global emergence of antibiotic-resistant strains from multiple classes has- reduced the number of drugs that still have activity against this pathogen. The lack of A. baumannii isolates that produce carbapenemase in addition to having a minimal inhibitory concentration of imipenem greater than carbapenem resistance. The overview of the prevalence of Acinetobacter in the Indian scenario and world scenario. Comparision between carbapenem resistance and multidrug resistance. According to the studies, carbapenem resistance is rapidly increasing. Infection with Acinetobacter is linked to high mortality and morbidity. According to our review, patients who have an infection with A. baumannii may be at an increased risk of dying. However, due to the confounding factors of illness severity, inappropriate impractical antimicrobial treatment, and small sample size, cautious interpretations are necessary. We covered the main factor that make A. baumannii such a prevalent nosocomial pathogen in this review, including such as its virulence components, desiccation resistance, and carbapenem resistance mechanisms. With the emergence of extended resistance to even more recent antibiotics, Acinetobacter species are rapidly proliferating. They can develop resistance much more quickly than other gram-negative organisms.

Detection of exopolysaccharides (algD, pelF, and pslD) genes in burn wound Pseudomonas aeruginosa isolates

Abstract Background: Pseudomonas aeruginosa biofilm is an essential component of virulence that plays a significant role in antimicrobial resistance and chronic burn wound infections. Objective: This study aimed to investigate the biofilm formation capacity of P. aeruginosa isolated from chronic burn wound from January to May 2022 by biochemical and molecular techniques. Materials and Methods: Quantification of biofilm was performed based on tube method for local isolates of P. aeruginosa after growing on brain heart Broth. The genes encoding exopolysaccharides (algD, pelF, and pslD) were targeted by using conventional polymerase chain reaction (PCR). Results: The results showed that 92.6% of isolates were biofilm former, interestingly 68% of isolates were considered as strong former comparing with other biofilm categories. Gel electrophoresis result of PCR products presented clear bands for algD and psID genes with percentages (96%) and (3.7%) respectively. However, there was no PCR product for pelf gene among all isolates. Conclusion: The prevalence of algD, the large operon necessary for alginate production, was high among P. aeruginosa biofilm producer in this study and it can be an essential agent in the pathogenicity of P. aeruginosa burn wound infections comparing with other biofilm genes (pelF and pslD) of exopolysaccharide structure.

Pseudomonas aeruginosa; Virulence Factors and Host Defense Mechanisms

As an opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa) can cause both acute and chronic infections. Variable virulence components and antibiotic resistance markers in the bacterium's genome constitute the bacterium's pathogenic profile and provide the bacterium with outstanding metabolic adaptability to many conditions. The interactions of P. aeruginosa with the host are poorly understood, complicating the treatment of its infections and the development of vaccines against them. Despite decades of scientific research focusing specifically on this challenge, vaccines to prevent these dangerous infections still do not exist. The major virulence factors of P. aeruginosa and host immune responses against the bacteria are discussed in this review.

Overexpression of Pasteurella multocida OmpA induces transcriptional changes and its possible implications for the macrophage polarization

Pasteurella multocida (P. multocida) is a highly infectious, zoonotic pathogen. Outer membrane protein A (OmpA) is an important virulence component of the outer membrane of P. multocida. OmpA mediates bacterial biofilm formation, eukaryotic cell infection, and immunomodulation. It is unclear how OmpA affects the host immune response. We estimated the role of OmpA in the pathogenesis of P. multocida by investigating the effect of OmpA on the immune cell transcriptome. Changes in the transcriptome of rat alveolar macrophages (NR8383) upon overexpression of P. multocida OmpA were demonstrated. A model cell line for stable transcription of OmpA was constructed by infecting NR8383 cells with OmpA-expressing lentivirus. RNA was extracted from cells and sequenced on an Illumina HiSeq platform. Key gene analysis of genes in the RNA-seq dataset were performed using various bioinformatics methods, such as gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, and Protein–Protein Interaction Analysis. Our findings revealed 1340 differentially expressed genes. Immune-related pathways that were significantly altered in rat alveolar macrophages under the effect of OmpA included focal adhesion, extracellular matrix and vascular endothelial growth factor signaling pathways, antigen processing and presentation, nucleotide oligomerization domain-like receptor and Toll-like receptor signaling pathways, and cytokine-cytokine receptor interaction. The key genes screened were Vegfa, Igf2r, Fabp5, P2rx1, C5ar1, Nedd4l, Gas6, Cxcl1, Pf4, Pdgfb, Thbs1, Col7a1, Vwf, Ccl9, and Arg1. Data of associated pathways and altered gene expression indicated that OmpA might cause the conversion of rat alveolar macrophages to M2-like. The related pathways and key genes can serve as a reference for OmpA of P. multitocida and host interaction mechanism studies.

Antimicrobial Sensitivity of Salmonella Species in Children - A Single-Centered Study

Background: Salmonellae are gram-negative, facultative anaerobic bacteria. Typhoid fever has a non-specific and varied appearance in its early stages. A high-grade fever (>38oC) is the most common presenting sign. Salmonella pathogenicity is primarily determined bythe virulence components it possesses, such as Salmonella pathogenicity islands (SPIs), virulence plasmids, pili, and enterotoxins.The most common drug used was cefixime (66.6%), then ciprofloxacin, and according to a comparable study conducted in Pakistan (33.3%). Cefixime and ceftriaxone had a sensitivity of 60.9% and 65.8%, respectively. In 50.1% of S.typhi isolates, ciprofloxacin sensitivity was observed. Aim: To determine the frequency of the most common salmonella specie and its drug sensitivity in children. Methodology:This descriptive study was conducted in the Department of Pediatrics Bacha Khan Medical Complex Swabi from April 2022 to October 2022 in children with suspected enteric fever. Blood culture reports of suspected patients were sent to the laboratory and reports were followed, before reports arrived patients were started on antibiotics. The sensitivity of drugs was measured by calculating frequency and percentages. Results: This study was conducted on 63 children having blood culture reports presented to us with suspected enteric fever including 25 females and 38 males with a mean age of 6.4±27 years. The most common organism in the blood culture of children presented with enteric fever was salmonella typhi (95.2%). Salmonella paratyphoid species shows 100% sensitivity to co-triaxle, co-trimoxazole and amikacin while 50.8% to azithromycin. Salmonella paratyphi A with 100% sensitivity to amikacin, ampicillin, azithromycin, cefepime, cefoperazone, cefotaxime, co-amoxiclav and colistin. While salmonella typhi were found to be 95.2% with drugs sensitivity amikacin, colistin, fosfomycin, co-trimoxazole, and ertapenem (100%) and ciprofloxacin (73%). Practical implication: by knowing the most common organism and its drug’s sensitivity and resistance, the resistance to antibiotics will be reduced, and targeted antibiotics will be used. Conclusion: Salmonella typhiwas the most common pathogen detected in blood culture (95.2%) with 100%drug sensitivity to amikacin, colistin, fosfomycin, co-trimoxazole, and ertapenem. Keywords: Salmonellatyphi, sensitivity, blood culture, children, enteric fever

Virulence variability and genetic diversity in Blumeria graminis f. sp. hordei in southeastern and southwestern China.

Powdery mildew is a key airborne foliar disease of barley in southeastern and southwestern China. Barley varieties usually partially or wholly lose resistance to the pathogen Blumeria graminis (DC.) f. sp. hordei (Bgh) three to five years after release due to the frequent acquirements of new virulences in the pathogen population. However, no Bgh virulence detection has been carried out in the recent decade, and thus no information is available on the present virulence components and major pathotypes in epidemic regions. Twenty-one near-isogenic lines (NILs) of Pallas were selected to detect Bgh virulence variation, with 97 pathotypes identified from the isolates collected from 2015 to 2019. The virulence complexities ranged from one to 12, with 1.5 isolates on average assigned per pathotype, suggesting a natural trait of high pathotype diversity and low virulence complexity (VC) in the Chinese Bgh populations. Eleven high virulence pathotypes were detected in the traditional barley-growing regions in Yunnan and Zhejiang. Six virulent pathotypes to resistance gene mlo-5 were detected only in the two traditional epidemic regions, with a virulence frequency (VF) of 4.8% (7/147). Compared to the results from a decade ago, VFs for resistance alleles Mla3, mlo-5, Mla6 + Mla14, Mla7 + Mlk, Mlg + MlCP, and Mla13 + MlRu3 + MlaRu4 increased from zero to 0.7 to 25.8%. Isolates from Yunnan and Zhejiang had similar virulence profiles, which differed from those identified in Tibet. In addition, genetic diversities differed in the isolate groups collected from Tibet, Yunnan, and Zhejiang.

An Insight into MptpB Inhibitors as a Key Strategy to Treat MDR and XDRTuberculosis.

Tuberculosis (TB) is a chronic, air-borne infectious disease caused by Mycobacterium tuberculosis (Mtb), which prominently affects the lungs and usually manifests in other organs. TB is preventable and curable but what makes it challenging is the emergence of resistance to the available treatment options. MDR-continued TB's expansion is one of the world's most pressing and difficult problems. Mtb revives via the reciprocity between Mycobacterium and host signalling pathways. Mtb secretes a virulence component called Mycobacterium tuberculosis protein tyrosine phosphatase (MptpB), which helps to survive against host macrophages. It indicates that targeting secreted virulence factors offers more benefits to circumvent the emergence of resistance. Many effective inhibitors of MptpA and MptpB have been discovered, providing a solid foundation for future research and development. Aside from possessing a structurally unique binding site in the Mtb enzyme, MptpB's minimal resemblance to other human phosphatases provides a broad platform for improving selectivity over host PTPs. We believe that addressing several parts of infection processes in the host and bacteria with combination therapy is the greatest way to reduce treatment burden and medication resistance. We have discussed the recent potent, selective, and efficacious MptpB inhibitors, such as natural and marine-based, isoxazole- linked carboxylic acid-based, oxamic acid-based, and lactone-based inhibitors, as potential strategies for treating TB.

High virulence is associated with pathogen spreadability in a songbird-bacterial system.

How directly transmitted pathogens benefit from harming hosts is key to understanding virulence evolution. It is recognized that pathogens benefit from high within-host loads, often associated with virulence. However, high virulence may also directly augment spread of a given amount of pathogen, here termed 'spreadability'. We used house finches and the conjunctival pathogen Mycoplasma gallisepticum to test whether two components of virulence-the severity of conjunctival inflammation and behavioural morbidity produced-predict pathogen spreadability. We applied ultraviolet powder around the conjunctiva of finches that were inoculated with pathogen treatments of distinct virulence and measured within-flock powder spread, our proxy for 'spreadability'. When compared to uninfected controls, birds infected with a high-virulence, but not low-virulence, pathogen strain, spread significantly more powder to flockmates. Relative to controls, high-virulence treatment birds both had more severe conjunctival inflammation-which potentially facilitated powder shedding-and longer bouts on feeders, which serve as fomites. However, food peck rates and displacements with flockmates were lowest in high-virulence treatment birds relative to controls, suggesting inflammatory rather than behavioural mechanisms likely drive augmented spreadability at high virulence. Our results suggest that inflammation associated with virulence can facilitate pathogen spread to conspecifics, potentially favouring virulence evolution in this system and others.

Resistência horizontal e vertical da bananeira ao nematoide cavernícola depende do nível de agressividade ou da virulência da população do nematoide

Abstract The burrowing nematode Radopholus similis is among the most damaging pathogens. Resistant plants are one of the most promising approaches for nematode control, and knowledge of resistance and aggressiveness components is essential to understand resistance genetics and developing new cultivars. Therefore, this study aimed to assess the degree of resistance of eight banana accessions to populations of R. similis to verify differences in the reproduction capacity between nematode populations and to study the horizontal/vertical resistance and aggressiveness/ virulence components of Musa spp. and R. similis pathosystem. The accessions 4249-05, 4279-06, Yangambi Km5, 0323-03, 0337-02, 1304-06, Borneo and Grande Naine were inoculated with one of three R. similis populations from the Brazilian states of Pernambuco, Distrito Federal, and Santa Catarina and kept in a greenhouse. Accessions 4249-05, Yangambi Km5, 0323-03, and 4279-06 showed different resistance levels, and the Pernambuco population had the highest reproductive capacity. Using Griffing Model IV, evidence of vertical and horizontal resistance was observed, with accessions 4249-05 and Yangambi km5 showing the highest levels of horizontal resistance.

Quorum Sensing Based Drug Screening Against Vibrio Cholerae

The QS method is a means of bacterial cell-to-cell communication, which uses extracellular signal molecules called autoinducers to transmit information between cells.Bacteria can use QS to collaborate on tasks. The pathogen Vibrio cholerae uses QS to inhibit the development of virulence factors and the formation of biofilms. Cholera is caused by the Gram-negative, curved bacteria Vibrio cholerae (Clemens et al., 2017). There are also a number of virulence components produced by this disease, including cholera hemolysin (CH), toxin-co-regulated pilus (TCP), flagellum, etc. By constraining the target protein, HapR, with adequate bioactive compounds, the pathogenic activity of in vibrio cholerae can be suppressed.Bioactive substances from various natural food sources were chosen and analysed for their quorum quenching effect against HapR protein utilising bioinformatics methods. The in-silico analysis produced notable results for thirteen of the 25 substances evaluated, with the best docking score. These chemicals could be employed for QSI-based therapeutics against vibrio cholerae infections and could be suggested for in vitro and in vivo investigations.