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Potential immunological and genetic markers associated with lupus nephritis: From pathogenicity to therapeutic drug target

Sharafaldin ENK, Huri HZ, Sim MS, Lim SK

Autoimmun Rev, 2023 Dec;22(12):103406.
PMID: 37574180 DOI: 10.1016/j.autrev.2023.103406
Matched MeSH terms: Virulence
The chaperone Lhs1 contributes to the virulence of the fish-pathogenic oomycete Aphanomyces invadans

Iberahim NA, Sood N, Pradhan PK, van den Boom J, van West P, Trusch F

Fungal Biol, 2020 12;124(12):1024-1031.
PMID: 33213782 DOI: 10.1016/j.funbio.2020.09.003

Oomycetes are fungal-like eukaryotes and many of them are pathogens that threaten natural ecosystems and cause huge financial losses for the aqua- and agriculture industry. Amongst them, Aphanomyces invadans causes Epizootic Ulcerative Syndrome (EUS) in fish which can be responsible for up to 100% mortality in aquaculture. As other eukaryotic pathogens, in order to establish and promote an infection, A. invadans secretes proteins, which are predicted to overcome host defence mechanisms and interfere with other processes inside the host. We investigated the role of Lhs1 which is part of an ER-resident complex that generally promotes the translocation of proteins from the cytoplasm into the ER for further processing and secretion. Interestingly, proteomic studies reveal that only a subset of virulence factors are affected by the silencing of AiLhs1 in A. invadans indicating various secretion pathways for different proteins. Importantly, changes in the secretome upon silencing of AiLhs1 significantly reduces the virulence of A. invadans in the infection model Galleriamellonella. Furthermore, we show that AiLhs1 is important for the production of zoospores and their cluster formation. This renders proteins required for protein ER translocation as interesting targets for the potential development of alternative disease control strategies in agri- and aquaculture.

Matched MeSH terms: Virulence*
Covid-19 variants: Impact on transmissibility and virulence

Malik YA

Malays J Pathol, 2022 Dec;44(3):387-396.
PMID: 36591708

The genetic evolution of SARS-CoV-2 began in February 2020, with G614 spike protein strains superseding D614 strains globally. Since then with each subsequent mutations, the SARS-CoV-2 variants of concern, namely Alpha, Beta, Gamma, Delta and Omicron, superseded the previous one to become the dominant strain during the pandemic. By the end of November 2022, the Omicron variant and its descendent lineages account for 99.9% of sequences reported globally. All five VOCs have mutations located in the RBD of the spike protein, resulting in increased affinity of the spike protein to the ACE2 receptors resulting in enhanced viral attachment and its subsequent entry into the host cells. In vitro studies showed the mutations in spike protein help increase the viral fitness, enhancing both transmissibility and replication. In general, Alpha, Beta, Gamma, and Delta variants, were reported with higher transmissibility of 43-90%, around 50%, 170-240%, or 130-170% than their co-circulating VOCs, respectively. The Omicron however was found to be 2.38 times and 3.20 times more transmissible than Delta among the fully-vaccinated and boostervaccinated households. Even the SARS-Cov-2 Omicron subvariants appear to be inherently more transmissible than the ones before. With the broader distribution, enhanced evasion, and improved transmissibility, SARS-CoV-2 variants infection cause severe diseases due to immune escape from host immunity and faster replication. Reports have shown that each subsequent VOC, except Omicron, cause increased disease severity compared with those infected with other circulating variants. The Omicron variant infection however, appears to be largely associated with a lower risk of hospitalisation, ICU admission, mechanical ventilation, and even a shorter length of hospital stay. It has been shown that the relatively much slower replication of the Omicron variants in the lung, resulted in a less severe disease.

Matched MeSH terms: Virulence/genetics
Fulltext Transcriptional landscape of Burkholderia pseudomallei cultured under environmental and clinical conditions

Kong C, Wong RR, Ghazali AK, Hara Y, Tengku Aziz TN, Nathan S

Microb Genom, 2023 Apr;9(4).
PMID: 37018040 DOI: 10.1099/mgen.0.000982

Burkholderia pseudomallei, a Gram-negative pathogen, is the causative agent of melioidosis in humans. This bacterium can be isolated from the soil, stagnant and salt-water bodies, and human and animal clinical specimens. While extensive studies have contributed to our understanding of B. pseudomallei pathogenesis, little is known about how a harmless soil bacterium adapts when it shifts to a human host and exhibits its virulence. The bacterium's large genome encodes an array of factors that support the pathogen's ability to survive under stressful conditions, including the host's internal milieu. In this study, we performed comparative transcriptome analysis of B. pseudomallei cultured in human plasma versus soil extract media to provide insights into B. pseudomallei gene expression that governs bacterial adaptation and infectivity in the host. A total of 455 genes were differentially regulated; genes upregulated in B. pseudomallei grown in human plasma are involved in energy metabolism and cellular processes, whilst the downregulated genes mostly include fatty acid and phospholipid metabolism, amino acid biosynthesis and regulatory function proteins. Further analysis identified a significant upregulation of biofilm-related genes in plasma, which was validated using the biofilm-forming assay and scanning electron microscopy. In addition, genes encoding known virulence factors such as capsular polysaccharide and flagella were also overexpressed, suggesting an overall enhancement of B. pseudomallei virulence potential when present in human plasma. This ex vivo gene expression profile provides comprehensive information on B. pseudomallei's adaptation when shifted from the environment to the host. The induction of biofilm formation under host conditions may explain the difficulty in treating septic melioidosis.

Matched MeSH terms: Virulence; Virulence Factors
ACE2 role in SARS-CoV-2 infectivity and Covid-19 severity

Azizan E, Brown M

Malays J Pathol, 2020 Dec;42(3):363-367.
PMID: 33361716

In 2003, it was discovered that the entry receptor for the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) is a protein called the angiotensin-converting enzyme 2 (ACE2). This protein is present in a number of cell types, including those from the respiratory tract. Soon after the emergence of SARS-CoV-2 that is responsible for the disease Covid-19, scientists found that ACE2 was also used by the new coronavirus to infect cells. This opened some interesting possibilities to explain the striking variation in risks of catching and dying from Covid-19. The best recognised of these are the much higher risk of serious illness in older than younger people, in men than women, and in those with pre-existing comorbidities such as hypertension and cardiovascular diseases. There are several ways in which the ACE2 protein might contribute to this variation. The most obvious would be if there is more ACE2, there would be more entry points for the virus to infect the cell, e.g. in older people or in men. However, the evidence for this is rather small, partly because it is not that easy to obtain representative healthy tissues. Alternatively, it could be related to ACE2 membership of a family of proteins that has one end of the protein anchored inside the cell while most of the protein protrudes from the outside of the cell which therefore can be shed when cleaved by proteases at the cell membrane. Herein we review current evidence and theories of ACE2 role on SARS-CoV-2 infectivity and Covid-19 severity.

Matched MeSH terms: Virulence
Characterization and Comparative Overview of Complete Sequences of the First Plasmids of Pandoraea across Clinical and Non-clinical Strains

Yong D, Tee KK, Yin WF, Chan KG

Front Microbiol, 2016;7:1606.
PMID: 27790203

To date, information on plasmid analysis in Pandoraea spp. is scarce. To address the gap of knowledge on this, the complete sequences of eight plasmids from Pandoraea spp. namely Pandoraea faecigallinarum DSM 23572(T) (pPF72-1, pPF72-2), Pandoraea oxalativorans DSM 23570(T) (pPO70-1, pPO70-2, pPO70-3, pPO70-4), Pandoraea vervacti NS15 (pPV15) and Pandoraea apista DSM 16535(T) (pPA35) were studied for the first time in this study. The information on plasmid sequences in Pandoraea spp. is useful as the sequences did not match any known plasmid sequence deposited in public databases. Replication genes were not identified in some plasmids, a situation that has led to the possibility of host interaction involvement. Some plasmids were also void of par genes and intriguingly, repA gene was also not discovered in these plasmids. This further leads to the hypothesis of host-plasmid interaction. Plasmid stabilization/stability protein-encoding genes were observed in some plasmids but were not established for participating in plasmid segregation. Toxin-antitoxin systems MazEF, VapBC, RelBE, YgiT-MqsR, HigBA, and ParDE were identified across the plasmids and their presence would improve plasmid maintenance. Conjugation genes were identified portraying the conjugation ability amongst Pandoraea plasmids. Additionally, we found a shared region amongst some of the plasmids that consists of conjugation genes. The identification of genes involved in replication, segregation, toxin-antitoxin systems and conjugation, would aid the design of drugs to prevent the survival or transmission of plasmids carrying pathogenic properties. Additionally, genes conferring virulence and antibiotic resistance were identified amongst the plasmids. The observed features in the plasmids shed light on the Pandoraea spp. as opportunistic pathogens.

Matched MeSH terms: Virulence
Characterization of Campylobacter jejuni and Campylobacter coli isolates from chicken offal in Metro Manila, Philippines: Insights from virulence gene prevalence and multilocus sequence typing analysis

Subejano MSE, Penuliar G

Trop Biomed, 2023 Dec 01;40(4):422-429.
PMID: 38308829 DOI: 10.47665/tb.40.4.007

Campylobacteriosis is a human infection primarily caused by Campylobacter jejuni and Campylobacter coli. Consumption of contaminated chicken and poultry products is the main mode of transmission. These bacteria possess virulence factors, including adhesins and toxins, which contribute to their pathogenesis. Moreover, their large genomes undergo frequent genetic recombination, resulting in a high degree of genetic diversity. However, limited information is available regarding the virulence and genotypic diversity profiles of these microorganisms in the Philippines. The objective of this study was to address this knowledge gap by characterizing Campylobacter isolates obtained from chicken offal sold in wet markets in Metro Manila, Philippines. Multilocus Sequence Typing (MLST) analysis was performed to determine the sequence types, resulting in the identification of 13 unique sequence types, including nine previously unreported ones, and three clonal complexes. Notably, the widespread sequence type ST-305 was found in samples from different markets. Furthermore, six isolates deposited in the Campylobacter PubMLST database were identified as C. coli based on allele profiles. Profiling using 10 selected virulence genes revealed that more than half of the isolates carried these genes. The most prevalent virulence gene was cadF (100%), followed by flaA (95%), racR, cdtA, cdtB, and cdtC (85%). The genes dnaJ and ceuE were also present in 75% of the isolates. Despite the limited sample size, the findings of this study reveal a significant level of genotypic diversity among the Campylobacter isolates. This diversity has important implications for source attribution studies and the identification of strains involved in campylobacteriosis outbreaks. Furthermore, the investigation of virulence factors associated with colonization and invasion of the avian gut can provide insights for the development of practical applications in Campylobacter control strategies. Understanding and addressing these factors are crucial steps toward mitigating the risk of Campylobacter infections and enhancing public health efforts.

Matched MeSH terms: Virulence/genetics; Virulence Factors/genetics
Cross-pathogenicity of Phytophthora palmivora associated with bud rot disease of oil palm and development of biomarkers for detection

Maizatul-Suriza M, Dickinson M, Al-Jaf B, Madihah AZ

World J Microbiol Biotechnol, 2024 Jan 02;40(2):55.
PMID: 38165501 DOI: 10.1007/s11274-023-03860-5

Phytophthora palmivora has caused disease in many crops including oil palm in the South America region. The pathogen has had a significant economic impact on oil palm cultivation in Colombia, and therefore poses a threat to oil palm cultivation in other regions of the World, especially in Southeast Asia, the largest producer of the crop. This study aimed to look at the ability of isolates from Malaysia, Colombia, and other regions to cross-infect Malaysian oil palm, durian, and cocoa and to develop specific biomarkers and assays for identification, detection, and diagnosis of P. palmivora as a key component for the oil palm biosecurity continuum in order to contain the disease especially at the ports of entry. We have developed specific molecular biomarkers to identify and detect Phytophthora palmivora using polymerase chain reaction (PCR) and real-time loop mediated isothermal amplification (rt-LAMP) in various sample types such as soil and plants. The limit of detection (DNA template, pure culture assay) for the PCR assay is 5.94 × 10-2 ng µl-1 and for rt-LAMP is 9.28 × 10-4 ng µl-1. Diagnosis using rt-LAMP can be achieved within 30 min of incubation. In addition, PCR primer pair AV3F/AV3R developed successfully distinguished the Colombian and Malaysian P. palmivora isolates.

Matched MeSH terms: Virulence
Enolase in Meyerozyma guilliermondii strain SO: Sequential and structural insights of MgEno4581 as a putative virulence factor and host-fungal interactions through comprehensive in silico approaches

Amran AI, Lim SJ, Muhd Noor ND, Salleh AB, Oslan SN

Microb Pathog, 2023 Mar;176:106025.
PMID: 36754101 DOI: 10.1016/j.micpath.2023.106025

Meyerozyma guilliermondii is a rare opportunistic fungal pathogen that causes deadly invasive candidiasis in human. M. guilliermondii strain SO is a local yeast isolate that possesses huge industrial interests but also pathogenic towards zebrafish embryos. Enolases that bind to human extracellular matrix (ECM) proteins are among the fungal virulence factors. To understand its pathogenicity mechanism down to molecular level, especially in the rare M. guilliermondii, this study aimed to identify and characterize the potentially virulence-associated enolase in M. guilliermondii strain SO using bioinformatics approaches. Profile Hidden-Markov model was implemented to identify enolase-related sequences in the fungal proteome. Sequence analysis deciphered only one (MgEno4581) out of nine sequences exhibited potent virulence traits observed similarly in the pathogenic Candida albicans. MgEno4581 structure that was predicted via SWISS-MODEL using C. albicans enolase (CaEno1; PDB ID: 7vrd) as the homology modeling template portrayed a highly identical motif with CaEno1 that facilitates ECM proteins binding. Amino acid substitutions (D234K, K235A, Y238H, K239D, G243K, V248C and Y254F) in ECM-binding motif of Saccharomyces cerevisiae enolase (ScEno) compared to MgEno4581 and CaEno1 caused changes in motif's surface charges. Protein-protein docking indicated F253 in ScEno only interacted hydrophobically with human plasminogen (HPG). Hydrogen linkages were observed for both MgEno4581 and CaEno1, suggesting a stronger interaction with HPG in the hydrophilic host microenvironments. Thus, our in silico characterizations on MgEno4581 provided new perspectives on its potential roles in candidiasis (fungal-host interactions) caused by M. guilliermondii, especially M. guilliermondii strain SO on zebrafish embryos that mimic the immunocompromised individuals as previously evident.

Matched MeSH terms: Virulence Factors*
Fulltext Genotypic characteristics of Uropathogenic Escherichia coli isolated from complicated urinary tract infection (cUTI) and asymptomatic bacteriuria-a relational analysis

Maniam L, Vellasamy KM, Ong TA, Teh CSJ, Jabar KA, Mariappan V, et al.

PeerJ, 2023;11:e15305.
PMID: 37361034 DOI: 10.7717/peerj.15305

BACKGROUND: Uropathogenic Escherichia coli (UPEC) is the predominant agent causing various categories of complicated urinary tract infections (cUTI). Although existing data reveals that UPEC harboured numerous virulence determinants to aid its survival in the urinary tract, the reason behind the occurrence of differences in the clinical severity of uninary tract infections (UTI) demonstrated by the UPEC infection is poorly understood. Therefore, the present study aims to determine the distribution of virulence determinants and antimicrobial resistance among different phylogroups of UPEC isolated from various clinical categories of cUTI and asymptomatic bacteriuria (ASB) E. coli isolates. The study will also attempt a relational analysis of the genotypic characteristics of cUTI UPEC and ASB E. coli isolates.
METHODS: A total of 141 UPEC isolates from cUTI and 160 ASB E. coli isolates were obtained from Universiti Malaya Medical Centre (UMMC). Phylogrouping and the occurrence of virulence genes were investigated using polymerase chain reaction (PCR). Antimicrobial susceptibility of the isolates to different classes of antibiotics was determined using the Kirby Bauer Disc Diffusion method.
RESULTS: The cUTI isolates were distributed differentially among both Extraintestinal Pathogenic E. coli (ExPEC) and non-ExPEC phylogroups. Phylogroup B2 isolates were observed to possess the highest average aggregative virulence score (7.17), a probable representation of the capability to cause severe disease. Approximately 50% of the cUTI isolates tested in this study were multidrug resistant against common antibiotics used to treat UTI. Analysis of the occurrence of virulence genes among different cUTI categories demonstrated that UPEC isolates of pyelonephritis and urosepsis were highly virulent and had the highest average aggregative virulence scores of 7.80 and 6.89 respectively, compared to other clinical categories. Relational analysis of the occurrence of phylogroups and virulence determinants of UPEC and ASB E. coli isolates showed that 46.1% of UPEC and 34.3% of ASB E. coli from both categories were distributed in phylogroup B2 and had the highest average aggregative virulence score of 7.17 and 5.37, respectively. The data suggest that UPEC isolates which carry virulence genes from all four virulence genes groups studied (adhesions, iron uptake systems, toxins and capsule synthesis) and isolates from phylogroup B2 specifically could predispose to severe UTI involving the upper urinary tract. Therefore, specific analysis of the genotypic characteristics of UPEC could be further explored by incorporating the combination of virulence genes as a prognostic marker for predicting disease severity, in an attempt to propose a more evidence driven treatment decision-making for all UTI patients. This will go a long way in enhancing favourable therapeutic outcomes and reducing the antimicrobial resistance burden among UTI patients.

Matched MeSH terms: Virulence Factors/genetics
A linking bridge between histopathological analysis and molecular assay in microbiology

Okubo Y

Malays J Pathol, 2017 08;39(2):207-208.
PMID: 28866707

No abstract available.

Matched MeSH terms: Virulence/genetics*; Virulence Factors/genetics*; Virulence Factors/metabolism
Genetic dynamics of Salmonella typhi--diversity in clonality

Pang T

Trends Microbiol., 1998 Sep;6(9):339-42.
PMID: 9778724
Matched MeSH terms: Virulence/genetics; Virulence/immunology
Fulltext Inhibiting N-acyl-homoserine lactone synthesis and quenching Pseudomonas quinolone quorum sensing to attenuate virulence

Chan KG, Liu YC, Chang CY

Front Microbiol, 2015;6:1173.
PMID: 26539190 DOI: 10.3389/fmicb.2015.01173

Bacteria sense their own population size, tune the expression of responding genes, and behave accordingly to environmental stimuli by secreting signaling molecules. This phenomenon is termed as quorum sensing (QS). By exogenously manipulating the signal transduction bacterial population behaviors could be controlled, which may be done through quorum quenching (QQ). QS related regulatory networks have been proven their involvement in regulating many virulence determinants in pathogenic bacteria in the course of infections. Interfering with QS signaling system could be a novel strategy against bacterial infections and therefore requires more understanding of their fundamental mechanisms. Here we review the development of studies specifically on the inhibition of production of N-acyl-homoserine lactone (AHL), a common proteobacterial QS signal. The opportunistic pathogen, Pseudomonas aeruginosa, equips the alkylquinolone (AQ)-mediated QS which also plays crucial roles in its pathogenicity. The studies in QQ targeting on AQ are also discussed.

Matched MeSH terms: Virulence; Virulence Factors
Fulltext PCR-based construction and transformation of CodY gene deletion construct in Streptococcus Pneumoniae

Aisyah Mohamed Rehan, Mohammad Izwan Enche Othman, Nor Munirah Mohd Amin, Intan Azura Shahdan, Hanani Ahmad Yusof@Hanafi

International Medical Journal Malaysia, 2017;16(11):7-7.
MyJurnal

Streptococcus pneumoniae (S. pneumoniae) is a gram-positive diplococci belonging to the genus Streptococcus and it is a well-studied pathogenic bacterium. Pneumococcal diseases such as otitis media, pneumonia, sepsis and meningitis caused by pathogenic strains of S. pneumoniae still brought significant mortality and morbidity worldwide. The pathogenicity of S. pneumoniae is exerted by various virulence factors and one of it is the enzyme hyaluronate lyase. Hyaluronate lyase plays a major role in
the invasive capability of S. pneumoniae. Its mechanism of action and crystallographic
structure have been determinedbut its regulatory mechanism is still poorly understood.
Drawing connections between the nutritional behaviour and invasive property of S.
pneumoniae, CodY regulator is hypothesized as a potential hyaluronate lyase regulator.
This work was aimed to construct CodY deficient mutant of S. pneumoniae to form
foundational work for the study of CodY regulatory effect on hyaluronate lyase.

Matched MeSH terms: Virulence; Virulence Factors
Genetic diversity and virulence characteristics of Helicobacter pylori isolates in different human ethnic groups

Hanafiah A, Lopes BS

Infect Genet Evol, 2020 Mar;78:104135.
PMID: 31837482 DOI: 10.1016/j.meegid.2019.104135

Helicobacter pylori is the most predominant bacterium in almost 50% of the world's population and colonization causes a persistent inflammatory response leading to chronic gastritis. It shows high genetic diversity and individuals generally harbour a distinct bacterial population. With the advancement of whole-genome sequencing technology, new H. pylori subpopulations have been identified that show admixture between various H. pylori strains. Genotypic variation of H. pylori may be related to the presence of virulence factors among strains and is associated with different outcomes of infection in different individuals. This review summarizes the genetic diversity in H. pylori strain populations and its virulence characteristics responsible for variable outcomes in different ethnic groups.

Matched MeSH terms: Virulence; Virulence Factors
Identification of sequence motifs for the protein components of type ix secretion system

Reeki Emrizal, Nor Azlan Nor Muhammad

Sains Malaysiana, 2018;47:2941-2950.

Porphyromonas gingivalis is the bacterium responsible for chronic periodontitis, a severe periodontal disease. Virulence
factors produced by this bacterium are secreted by the Type IX Secretion System (T9SS). The specific functions for
each protein component of the T9SS have yet to be characterized thus limiting our understanding of the mechanisms
associated with the translocation and modification processes of the T9SS. This study aims to identify the sequence motifs
for each T9SS component and predict the functions associated with each discovered motif using motif comparisons. We
extracted the sequences of 20 T9SS components from the P. gingivalis proteome that were experimentally identified to
be important for T9SS function and used them for homology searching against fully sequenced bacterial proteomes.
We developed a rigorous pipeline for the identification of seed sequences for each protein family of T9SS components.
We verified that each selected seed sequence are true members of the protein family hence sharing conserved sequence
motifs using profile Hidden Markov Models. The motifs for each T9SS component are identified and compared to motifs
in the Pfam database. The discovered motifs for 11 components with known functions matched the motifs associated
with the reported functions. We also suggested the putative functions for four components. PorM and PorW might form
the putative energy transduction complex. PorP and PorT might be the putative O-deacylases. The identified motifs for
five components matched the motifs associated with functions that related/unrelated to the T9SS.

Matched MeSH terms: Virulence
Fulltext Draft Genome Sequence of Blood Disease Bacterium A2 HR-MARDI, a Pathogen Causing Banana Bacterial Wilt

Badrun R, Abu Bakar N, Laboh R, Redzuan R, Bala Jaganath I

Genome Announc, 2017 Jun 01;5(22).
PMID: 28572313 DOI: 10.1128/genomeA.00408-17

Blood disease bacterium A2 HR-MARDI was isolated from banana plants infected with banana blood disease and which were planted in Kuala Kangsar, Malaysia. Here, we report a draft genome sequence of blood disease bacterium A2 HR-MARDI, which could provide important information on the virulence mechanism of this pathogen.

Matched MeSH terms: Virulence
Prevalence of Helicobacter pylori cagA, babA2, and dupA genotypes and correlation with clinical outcome in Malaysian patients with dyspepsia

Osman HA, Hasan H, Suppian R, Hassan S, Andee DZ, Abdul Majid N, et al.

Turk J Med Sci, 2015;45(4):940-6.
PMID: 26422871

BACKGROUND/AIM: The severity of disease outcome in dyspepsia has been attributed to Helicobacter pylori virulence genes. The aim of this study was to determine the distribution of H. pylori virulence genes (cagA, babA2, and dupA) and to determine whether or not there arises a significant correlation with clinical dyspepsia outcomes.
MATERIALS AND METHODS: H. pylori genotypes cagA, babA2, and dupA were identified by polymerase chain reactions from gastric biopsy samples in 105 H. pylori-positive patients.
RESULTS: The positive rates for cagA, babA2, and dupA genes in H. pylori dyspeptic patients were 69.5%, 41.0%, and 22.9%, respectivel cagA was more prevalent in Indians (39.7%), babA2 was more prevalent in Malays (39.5%), and dupA detection occurred more frequently in both Indians and Malays and at the same rate (37.5%). The Chinese inhabitants had the lowest prevalence of the three genes. Nonulcer disease patients had a significantly higher distribution of cagA (76.7%), babA2 (74.4%), and dupA (75.0%). There was no apparent association between these virulence genes and the clinical outcomes.
CONCLUSION: The lower prevalence of these genes and variations among different ethnicities implies that the strains are geographically and ethnically dependent. None of the virulence genes were knowingly beneficial in predicting the clinical outcome of H. pylori infection in our subjects.

Matched MeSH terms: Virulence/genetics; Virulence Factors/genetics*
Fulltext Gut bacteria influence Blastocystis sp. phenotypes and may trigger pathogenicity

Rajamanikam A, Isa MNM, Samudi C, Devaraj S, Govind SK

PLoS Negl Trop Dis, 2023 Mar;17(3):e0011170.
PMID: 36989208 DOI: 10.1371/journal.pntd.0011170

Whilst the influence of intestinal microbiota has been shown in many diseases such as irritable bowel syndrome, colorectal cancer, and aging, investigations are still scarce on its role in altering the nature of other infective organisms. Here we studied the association and interaction of Blastocystis sp. and human intestinal microbiota. In this study, we investigated the gut microbiome of Blastocystis sp.-free and Blastocystis sp. ST3-infected individuals who are symptomatic and asymptomatic. We tested if the expression of phenotype and pathogenic characteristics of Blastocystis sp. ST3 was influenced by the alteration of its accompanying microbiota. Blastocystis sp. ST3 infection alters bacterial composition. Its presence in asymptomatic individuals showed a significant effect on microbial richness compared to symptomatic ones. Inferred metagenomic findings suggest that colonization of Blastocystis sp. ST3 could contribute to the alteration of microbial functions. For the first time, we demonstrate the influence of bacteria on Blastocystis sp. pathogenicity. When Blastocystis sp. isolated from a symptomatic individual was co-cultured with bacterial suspension of Blastocystis sp. from an asymptomatic individual, the parasite demonstrated increased growth and reduced potential pathogenic expressions. This study also reveals that Blastocystis sp. infection could influence microbial functions without much effect on the microbiota diversity itself. Our results also demonstrate evidence on the influential role of gut microbiota in altering the characteristics of the parasite, which becomes the basis for the contradictory findings on the parasite's pathogenic role seen across different studies. Our study provides evidence that asymptomatic Blastocystis sp. in a human gut can be triggered to show pathogenic characteristics when influenced by the intestinal microbiota.

Matched MeSH terms: Virulence
Fulltext Aquatic Peptide: The Potential Anti-Cancer and Anti-Microbial Activity of GE18 Derived from Pathogenic Fungus Aphanomyces invadans

Velayutham M, Priya PS, Sarkar P, Murugan R, Almutairi BO, Arokiyaraj S, et al.

Molecules, 2023 Sep 21;28(18).
PMID: 37764521 DOI: 10.3390/molecules28186746

Small molecules as well as peptide-based therapeutic approaches have attracted global interest due to their lower or no toxicity in nature, and their potential in addressing several health complications including immune diseases, cardiovascular diseases, metabolic disorders, osteoporosis and cancer. This study proposed a peptide, GE18 of subtilisin-like peptidase from the virulence factor of aquatic pathogenic fungus Aphanomyces invadans, which elicits anti-cancer and anti-microbial activities. To understand the potential GE18 peptide-induced biological effects, an in silico analysis, in vitro (L6 cells) and in vivo toxicity assays (using zebrafish embryo), in vitro anti-cancer assays and anti-microbial assays were performed. The outcomes of the in silico analyses demonstrated that the GE18 peptide has potent anti-cancer and anti-microbial activities. GE18 is non-toxic to in vitro non-cancerous cells and in vivo zebrafish larvae. However, the peptide showed significant anti-cancer properties against MCF-7 cells with an IC50 value of 35.34 µM, at 24 h. Besides the anti-proliferative effect on cancer cells, the peptide exposure does promote the ROS concentration, mitochondrial membrane potential and the subsequent upregulation of anti-cancer genes. On the other hand, GE18 elicits significant anti-microbial activity against P. aeruginosa, wherein GE18 significantly inhibits bacterial biofilm formation. Since the peptide has positively charged amino acid residues, it targets the cell membrane, as is evident in the FESEM analysis. Based on these outcomes, it is possible that the GE18 peptide is a significant anti-cancer and anti-microbial molecule.

Matched MeSH terms: Virulence Factors

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