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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
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 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
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 Factors
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 Factors/genetics
Fulltext ATP-binding cassette (ABC) transporters: structures and roles in bacterial pathogenesis

How SS, Nathan S, Lam SD, Chieng S

J Zhejiang Univ Sci B, 2024 Oct 21;26(1):58-75.
PMID: 39815611 DOI: 10.1631/jzus.B2300641

Adenosine triphosphate (ATP)-binding cassette (ABC) transporter systems are divided into importers and exporters that facilitate the movement of diverse substrate molecules across the lipid bilayer, against the concentration gradient. These transporters comprise two highly conserved nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Unlike ABC exporters, prokaryotic ABC importers require an additional substrate-binding protein (SBP) as a recognition site for specific substrate translocation. The discovery of a large number of ABC systems in bacterial pathogens revealed that these transporters are crucial for the establishment of bacterial infections. The existing literature has highlighted the roles of ABC transporters in bacterial growth, pathogenesis, and virulence. These roles include importing essential nutrients required for a variety of cellular processes and exporting outer membrane-associated virulence factors and antimicrobial substances. This review outlines the general structures and classification of ABC systems to provide a comprehensive view of the activities and roles of ABC transporters associated with bacterial virulence and pathogenesis during infection.

Matched MeSH terms: Virulence Factors/metabolism
Fulltext Modulation of Host Biology by Pseudomonas aeruginosa Quorum Sensing Signal Molecules: Messengers or Traitors

Liu YC, Chan KG, Chang CY

Front Microbiol, 2015;6:1226.
PMID: 26617576 DOI: 10.3389/fmicb.2015.01226

Bacterial cells sense their population density and respond accordingly by producing various signal molecules to the surrounding environments thereby trigger a plethora of gene expression. This regulatory pathway is termed quorum sensing (QS). Plenty of bacterial virulence factors are controlled by QS or QS-mediated regulatory systems and QS signal molecules (QSSMs) play crucial roles in bacterial signaling transduction. Moreover, bacterial QSSMs were shown to interfere with host cell signaling and modulate host immune responses. QSSMs not only regulate the expression of bacterial virulence factors but themselves act in the modulation of host biology that can be potential therapeutic targets.

Matched MeSH terms: Virulence Factors
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 Factors/genetics*; Virulence Factors/metabolism
Fulltext Amoebic forms of Blastocystis spp. - evidence for a pathogenic role

Rajamanikam A, Govind SK

Parasit Vectors, 2013;6(1):295.
PMID: 24499467 DOI: 10.1186/1756-3305-6-295

Blastocystis spp. are one of the most prevalent parasites isolated from patients suffering from diarrhea, flatulence, constipation and vomiting. It's pathogenicity and pathophysiology remains controversial to date. Protease activity and amoebic forms have been reported previously in symptomatic isolates but there has been no conclusive evidence provided to correlate the protease activity and any specific life cycle stage of the parasite thus far.

Matched MeSH terms: Virulence Factors/metabolism*; Virulence Factors/chemistry
Fulltext Expression of Ascaris lumbricoides putative virulence-associated genes when infecting a human host

Mohd-Shaharuddin N, Lim YAL, Ngui R, Nathan S

Parasit Vectors, 2021 Mar 23;14(1):176.
PMID: 33757548 DOI: 10.1186/s13071-021-04680-y

BACKGROUND: Ascaris lumbricoides is the most common causative agent of soil-transmitted helminth infections worldwide, with an estimated 450 million people infected with this nematode globally. It is suggested that helminths are capable of evading and manipulating the host immune system through the release of a spectrum of worm proteins which underpins their long-term survival in the host. We hypothesise that the worm overexpresses these proteins when infecting adults compared to children to cirvumvent the more robust defence mechanisms of adults. However, little is known about the parasite's genes and encoded proteins involved during A. lumbricoides infection. Hence, this study was conducted to assess the expression profile of putative virulence-associated genes during an active infection of adults and children.
METHODS: In this study, quantitative PCR was performed to evaluate the expression profile of putative virulence-associated genes in A. lumbricoides isolated from infected children and adults. The study was initiated by collecting adult worms expelled from adults and children following anthelminthic treatment. High-quality RNA was successfully extracted from each of six adult worms expelled by three adults and three children, respectively. Eleven putative homologues of helminth virulence-associated genes reported in previous studies were selected, primers were designed and specific amplicons of A. lumbricoides genes were noted. The expression profiles of these putative virulence-associated genes in A. lumbricoides from infected adults were compared to those in A. lumbricoides from infected children.
RESULTS: The putative virulence-associated genes VENOM, CADHERIN and PEBP were significantly upregulated at 166-fold, 13-fold and fivefold, respectively, in adults compared to children. Conversely, the transcription of ABA-1 (fourfold), CATH-L (threefold) and INTEGRIN (twofold) was significantly suppressed in A. lumbricoides from infected adults.
CONCLUSIONS: On the basis of the expression profile of the putative virulence-associated genes, we propose that the encoded proteins have potential roles in evasion mechanisms, which could guide the development of therapeutic interventions.

Matched MeSH terms: Virulence Factors/genetics; Virulence Factors/immunology
Application of Spiroplasma melliferum proteogenomic profiling for the discovery of virulence factors and pathogenicity mechanisms in host-associated spiroplasmas

Alexeev D, Kostrjukova E, Aliper A, Popenko A, Bazaleev N, Tyakht A, et al.

J Proteome Res, 2012 Jan 1;11(1):224-36.
PMID: 22129229 DOI: 10.1021/pr2008626

To date, no genome of any of the species from the genus Spiroplasma has been completely sequenced. Long repetitive sequences similar to mobile units present a major obstacle for current genome sequencing technologies. Here, we report the assembly of the Spiroplasma melliferum KC3 genome into 4 contigs, followed by proteogenomic annotation and metabolic reconstruction based on the discovery of 521 expressed proteins and comprehensive metabolomic profiling. A systems approach allowed us to elucidate putative pathogenicity mechanisms and to discover major virulence factors, such as Chitinase utilization enzymes and toxins never before reported for insect pathogenic spiroplasmas.

Matched MeSH terms: Virulence Factors/genetics*; Virulence Factors/metabolism
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 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 Factors
Fulltext Electrostatic interactions at the five-fold axis alter heparin-binding phenotype and drive enterovirus A71 virulence in mice

Tee HK, Tan CW, Yogarajah T, Lee MHP, Chai HJ, Hanapi NA, et al.

PLoS Pathog, 2019 11;15(11):e1007863.
PMID: 31730673 DOI: 10.1371/journal.ppat.1007863

Enterovirus A71 (EV-A71) causes hand, foot and mouth disease epidemics with neurological complications and fatalities. However, the neuropathogenesis of EV-A71 remains poorly understood. In mice, adaptation and virulence determinants have been mapped to mutations at VP2-149, VP1-145 and VP1-244. We investigate how these amino acids alter heparin-binding phenotype and shapes EV-A71 virulence in one-day old mice. We constructed six viruses with varying residues at VP1-98, VP1-145 (which are both heparin-binding determinants) and VP2-149 (based on the wild type 149K/98E/145Q, termed KEQ) to generate KKQ, KKE, KEE, IEE and IEQ variants. We demonstrated that the weak heparin-binder IEE was highly lethal in mice. The initially strong heparin-binding IEQ variant acquired an additional mutation VP1-K244E, which confers weak heparin-binding phenotype resulting in elevated viremia and increased virus antigens in mice brain, with subsequent high virulence. IEE and IEQ-244E variants inoculated into mice disseminated efficiently and displayed high viremia. Increasing polymerase fidelity and impairing recombination of IEQ attenuated the virulence, suggesting the importance of population diversity in EV-A71 pathogenesis in vivo. Combining in silico docking and deep sequencing approaches, we inferred that virus population diversity is shaped by electrostatic interactions at the five-fold axis of the virus surface. Electrostatic surface charges facilitate virus adaptation by generating poor heparin-binding variants for better in vivo dissemination in mice, likely due to reduced adsorption to heparin-rich peripheral tissues, which ultimately results in increased neurovirulence. The dynamic switching between heparin-binding and weak heparin-binding phenotype in vivo explained the neurovirulence of EV-A71.

Matched MeSH terms: Virulence Factors/genetics; Virulence Factors/metabolism*; Virulence Factors/chemistry
Differential Gene Expression of Heat Shock Protein 90 (Hsp90) of Candida albicans obtained from Malaysian and Iranian Patients

Khalili V, Shokri H, Md Akim A, Khosravi AR

Malays J Med Sci, 2016 May;23(3):64-71.
PMID: 27418871

Candida albicans (C. albicans) has several virulence factors, in particular heat shock protein 90 (Hsp90), which is expressed by Hsp90 gene. The purposes of this study were to assess the expression of Hsp90 gene in clinical and control isolates of C. albicans obtained from different geographical regions (Malaysia and Iran), different temperatures (25°C, 37°C and 42°C) and mice with candidiasis.

Matched MeSH terms: Virulence Factors
Opportunistic yeast pathogen Candida spp.: Secreted and membrane-bound virulence factors

Lim SJ, Mohamad Ali MS, Sabri S, Muhd Noor ND, Salleh AB, Oslan SN

Med Mycol, 2021 Dec 03;59(12):1127-1144.
PMID: 34506621 DOI: 10.1093/mmy/myab053

Candidiasis is a fungal infection caused by Candida spp. especially Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Although the medicinal therapeutic strategies have rapidly improved, the mortality rate as candidiasis has continuously increased. The secreted and membrane-bound virulence factors (VFs) are responsible for fungal invasion, damage and translocation through the host enterocytes besides the evasion from host immune system. VFs such as agglutinin-like sequences (Als), heat shock protein 70, phospholipases, secreted aspartyl proteinases (Sap), lipases, enolases and phytases are mostly hydrolases which degrade or interact with the enterocyte membrane components. Candidalysin, however, acts as a peptide toxin to induce necrotic cell lysis. To date, structural studies of the VFs remain underexplored, hindering their functional analyses. Among the VFs, only Sap and Als have their structures deposited in Protein Data Bank (PDB). Therefore, this review scrutinizes the mechanisms of these VFs by discussing the VF-deficient studies of several Candida spp. and their abilities to produce these VFs. Nonetheless, their latest reported sequential and structural analyses are discussed to impart a wider perception of the host-pathogen interactions and potential vaccine or antifungal drug targets. This review signifies that more VFs structural investigations and mining in the emerging Candida spp. are required to decipher their pathogenicity and virulence mechanisms compared to the prominent C. albicans.
LAY SUMMARY: Candida virulence factors (VFs) including mainly enzymes and proteins play vital roles in breaching the human intestinal barrier and causing deadly invasive candidiasis. Limited VFs' structural studies hinder deeper comprehension of their mechanisms and thus the design of vaccines and antifungal drugs against fungal infections.

Matched MeSH terms: Virulence Factors
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 Factors
Identification of molecular determinants of cell culture growth characteristics of Enterovirus 71

Yee PT, Tan KO, Othman I, Poh CL

Virol J, 2016 11 28;13(1):194.
PMID: 27894305

BACKGROUND: Hand, foot and mouth disease is caused by Enterovirus 71 (EV-A71) and Coxsackieviruses. EV-A71 infection is associated with high fever, rashes and ulcers but more severe symptoms such as cardiopulmonary failure and death have been reported. The lack of vaccines highlighted the urgency of developing preventive agents against EV-A71. The molecular determinants of virulent phenotypes of EV-A71 is unclear. It remains to be investigated if specific molecular determinants would affect the cell culture growth characteristics of the EV-A71 fatal strain in Rhabdomyosarcoma (RD) cells.
RESULTS: In this study, several genetically modified sub-genotype B4 EV-A71 mutants were constructed by site-directed mutations at positions 158, 475, 486, 487 and 5262 or through partial deletion of the 5'-NTR region (∆ 11 bp from nt 475 to 486) to generate a deletion mutant (PD). EV-A71 mutants 475 and PD caused minimal cytopathic effects, produced lowest viral RNA copy number, viral particles as well as minimal amount of viral protein (VP1) in RD cells when compared to mutants 158, 486, 487 and 5262.
CONCLUSIONS: The molecular determinants of virulent phenotypes of EV-A71 sub-genotype B4 strain 41 (5865/Sin/000009) were found to differ from the C158 molecular determinant reported for the fatal EV-A71 sub-genotype B1 strain (clinical isolate 237). The site-directed mutations (SDM) introduced at various sites of the cDNA affected growth of the various mutants when compared to the wild type. Lowest viral RNA copy number, minimal number of plaques formed, higher infectious doses required for 50% lethality of RD cells and much reduced VP1 of the EV-A71 sub-genotype B4 strain 41 genome was attained in mutants carrying SDM at position 475 and through partial deletion of 11 bp at the 5'-NTR region.

Matched MeSH terms: Virulence Factors/genetics*
Fulltext Phylogeny and putative virulence gene analysis of Bartonella bovis

Tay ST, Kho KL, Lye SF, Ngeow YF

J Vet Med Sci, 2018 Apr 18;80(4):653-661.
PMID: 29311425 DOI: 10.1292/jvms.17-0448

Bartonella bovis is a small Gram-negative bacterium recognized as an etiological agent for bacteremia and endocarditis in cattle. As few reports are available on the taxonomic position of B. bovis and its mechanism of virulence, this study aims to resolve the phylogeny of B. bovis and investigate putative virulence genes based on whole genome sequence analysis. Genome-wide comparisons based on single nucleotide polymorphisms (SNP) and orthologous genes were performed in this study for phylogenetic inference of 27 Bartonella species. Rapid Annotation using Subsystem Technology (RAST) analysis was used for annotation of putative virulence genes. The phylogenetic tree generated from the genome-wide comparison of orthologous genes exhibited a topology almost similar to that of the tree generated from SNP-based comparison, indicating a high concordance in the nucleotide and amino acid sequences of Bartonella spp. The analyses show consistent grouping of B. bovis in a cluster related to ruminant-associated species, including Bartonella australis, Bartonella melophagi and Bartonella schoenbuchensis. RAST analysis revealed genes encoding flagellar components, in corroboration with the observation of flagella-like structure of BbUM strain under negative straining. Genes associated with virulence, disease and defence, prophages, membrane transport, iron acquisition, motility and chemotaxis are annotated in B. bovis genome. The flagellin (flaA) gene of B. bovis is closely related to Bartonella bacilliformis and Bartonella clarridgeiae but distinct from other Gram-negative bacteria. The absence of type IV secretion systems, the bona fide pathogenicity factors of bartonellae, in B. bovis suggests that it may have a different mechanism of pathogenicity.

Matched MeSH terms: Virulence Factors/genetics*
Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases

Kaur CP, Vadivelu J, Chandramathi S

J Dig Dis, 2018 May;19(5):262-271.
PMID: 29573336 DOI: 10.1111/1751-2980.12595

The 2016 Global Burden of Disease report by WHO revealed that diseases of the gastrointestinal tract (GIT) had one of the highest incidence rates worldwide. The plethora of factors that contribute to the development of GIT-related illnesses can be divided into genetic, environmental and lifestyle factors. Apart from that, the role that infectious agents play in the development of GIT diseases has piqued the interest of researchers worldwide. The human gut harbors approximately 1014 bacteria in it with increasing concentration toward the lower GIT. Among the various microbiota that colonize the human gut, Gram-negative bacteria have been most notoriously linked to GIT-related diseases such as inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis and colorectal cancer (CRC). Some of the notable culprits that have been attributed to these diseases are Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli and Helicobacter pylori. However, studies in recent years are beginning to recognize a new player, Klebsiella pneumoniae (K. pneumoniae) in the causation and progression of GIT diseases. Once synonymous with infections and diseases of the upper respiratory tract, K. pneumoniae has now emerged as one of the pathogens commonly isolated from patients with GIT diseases. However, extensive studies attributing K. pneumoniae to GIT diseases, particularly that of CRC are scanty. Therefore, this review intends to shed light on the association of K. pneumoniae in gastrointestinal diseases such as Crohn's disease, ulcerative colitis as well as CRC.

Matched MeSH terms: Virulence Factors/analysis

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