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  1. Fulltext Genetic diversity of Pantoea stewartii subspecies stewartii causing jackfruit-bronzing disease in Malaysia
    Abidin N, Ismail SI, Vadamalai G, Yusof MT, Hakiman M, Karam DS, et al.
    PLoS One, 2020;15(6):e0234350.
    PMID: 32530926 DOI: 10.1371/journal.pone.0234350
    Jackfruit-bronzing is caused by bacteria Pantoea stewartii subspecies stewartii (P. stewartii subsp. stewartii), showing symptoms of yellowish-orange to reddish discolouration and rusty specks on pulps and rags of jackfruit. Twenty-eight pure bacterial strains were collected from four different jackfruit outbreak collection areas in Peninsular Malaysia (Jenderam, Maran, Muadzam Shah and Ipoh). Positive P. stewartii subsp. stewartii verification obtained in the study was based on the phenotypic, hypersensitivity, pathogenicity and molecular tests. Multilocus sequence analysis (MLSA) was performed using four housekeeping genes (gyrB, rpoB, atpD and infB) on all 28 bacterial strains. Single gyrB, rpoB, atpD and infB phylogenetic trees analyses revealed the bootstrap value of 99-100% between our bacterial strains with P. stewartii subsp. stewartii reference strains and P. stewartii subsp. indologenes reference strains. On the other hand, phylogenetic tree of the concatenated sequences of the four housekeeping genes revealed that our 28 bacterial strains were more closely related to P. stewartii subsp. stewartii (99% similarities) compared to its close relative P. stewartii subsp. indologenes, although sequence similarity between these two subspecies were up to 100%. All the strains collected from the four collection areas clustered together, pointing to no variation among the bacterial strains. This study improves our understanding and provided new insight on the genetic diversity of P. stewartii subsp. stewartii associated with jackfruit-bronzing in Malaysia.
    Matched MeSH terms: Virulence/genetics
  2. 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
  3. Fulltext Helicobacter pylori Virulence Factor Cytotoxin-Associated Gene A (CagA)-Mediated Gastric Pathogenicity
    Ansari S, Yamaoka Y
    Int J Mol Sci, 2020 Oct 08;21(19).
    PMID: 33050101 DOI: 10.3390/ijms21197430
    Helicobacter pylori causes persistent infection in the gastric epithelium of more than half of the world's population, leading to the development of severe complications such as peptic ulcer diseases, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Several virulence factors, including cytotoxin-associated gene A (CagA), which is translocated into the gastric epithelium via the type 4 secretory system (T4SS), have been indicated to play a vital role in disease development. Although infection with strains harboring the East Asian type of CagA possessing the EPIYA-A, -B, and -D sequences has been found to potentiate cell proliferation and disease pathogenicity, the exact mechanism of CagA involvement in disease severity still remains to be elucidated. Therefore, we discuss the possible role of CagA in gastric pathogenicity.
    Matched MeSH terms: Virulence/genetics
  4. Enhanced intracellular survival and epithelial cell adherence abilities of Burkholderia pseudomallei morphotypes are dependent on differential expression of virulence-associated proteins during mid-logarithmic growth phase
    Al-Maleki AR, Mariappan V, Vellasamy KM, Shankar EM, Tay ST, Vadivelu J
    J Proteomics, 2014 Jun 25;106:205-20.
    PMID: 24742602 DOI: 10.1016/j.jprot.2014.04.005
    Colony morphology variation is a characteristic of Burkholderia pseudomallei primary clinical isolates, associated with variations in expression of virulence factors. Here, we performed comparative investigations on adhesion, invasion, plaque-forming abilities and protein profiles of B. pseudomallei wild-type (WT) and a small colony variant (SCV). The percentage of SCV adherence to A549 cells was significantly higher (2.73%) than WT (1.91%). In contrast, WT was significantly more efficient (0.63%) than SCV (0.31%) in invasiveness and in inducing cellular damage. Using 2-DE and MALDI TOF/TOF, 263 and 258 protein spots were detected in WT and SCV, respectively. Comparatively, 49 proteins were differentially expressed in SCV when compared with WT. Of these, 31 proteins were up-regulated, namely, nucleoside diphosphate kinase (Ndk), phosphoglycerate kinase (Pgk), thioredoxin (TrxA), putative ferritin DPS-family DNA-binding protein (DPS) and oxidoreductase (AhpC) that are known to be involved in adhesion, intracellular survival and persistence. However, among the 18 down-regulated proteins, enolase (Eno), elongation factor (EF-Tu) and universal stress-related proteins were associated with invasion and virulence. Differences observed in these protein profiles provide ample clues to their association with the morphotypic and phenotypic characteristics of colony variants, providing additional insights into the potential association of B. pseudomallei colony morphotypes with disease pathogenesis.
    Matched MeSH terms: Virulence/genetics
  5. Fulltext Prevalence and characterization of verotoxigenic-Escherichia coli isolates from pigs in Malaysia
    Ho WS, Tan LK, Ooi PT, Yeo CC, Thong KL
    BMC Vet Res, 2013;9:109.
    PMID: 23731465 DOI: 10.1186/1746-6148-9-109
    Postweaning diarrhea caused by pathogenic Escherichia coli, in particular verotoxigenic E. coli (VTEC), has caused significant economic losses in the pig farming industry worldwide. However, there is limited information on VTEC in Malaysia. The objective of this study was to characterize pathogenic E. coli isolated from post-weaning piglets and growers with respect to their antibiograms, carriage of extended-spectrum beta-lactamases, pathotypes, production of hemolysins and fimbrial adhesins, serotypes, and genotypes.
    Matched MeSH terms: Virulence/genetics
  6. Biofilm-Related Diseases and Omics: Global Transcriptional Profiling of Enterococcus faecium Reveals Different Gene Expression Patterns in the Biofilm and Planktonic Cells
    Lim SY, Teh CSJ, Thong KL
    OMICS, 2017 10;21(10):592-602.
    PMID: 29049010 DOI: 10.1089/omi.2017.0119
    Enterococcus faecium is an opportunistic pathogen with a remarkable ability to acquire resistance toward multiple antibiotics, including those of last-resort drugs such as vancomycin and daptomycin. The occurrence of vancomycin-resistant E. faecium is on the rise and there is a need to understand the virulence of this organism. One of the factors that contributes to the virulence is the ability to form biofilms. Since bacteria in biofilm state are more resistant to antibiotics and host immune response, understanding the molecular mechanism of biofilm development is important to control biofilm-related diseases. The aim of this study was to determine the global gene expression profiles of an E. faecium strain, VREr5, during the early event of sessile growth compared with its planktonic phase through RNA-sequencing approach. The results clearly illustrated distinct expression profiles of the planktonic and biofilm cells. A total of 177 genes were overexpressed in the biofilm cells. Most of them encode for proteins involved in adherence, such as the ebpABCfm locus. Genes associated with plasmid replication, gene exchange, and protein synthesis were also upregulated during the early event of biofilm development. Furthermore, the transcriptome analysis also identified genes such as fsrB, luxS, and spx that might suppress biofilm formation in VREr5. The putative biofilm-related bee locus was found to be downregulated. These new findings could provide caveats for future studies on the regulation and maintenance of biofilm and development of biomarkers for biofilm-related diseases.
    Matched MeSH terms: Virulence/genetics
  7. Fulltext Multiple-locus variable-number tandem repeat analysis of Vibrio cholerae in comparison with pulsed field gel electrophoresis and virulotyping
    Teh CS, Chua KH, Thong KL
    J Biomed Biotechnol, 2010;2010:817190.
    PMID: 20671932 DOI: 10.1155/2010/817190
    Molecular analysis of Malaysian Vibrio cholerae was carried out using a multiple-locus variable-number tandem repeat analysis (MLVA) assay based on 7 loci of V. cholerae. The discriminatory ability of the assay was compared with pulsed-field gel electrophoresis (PFGE) using 43 Malaysian V. cholerae isolated from various sources. In addition, the virulotypes of the strains were determined. Based on MLVA, 38 allelic profiles were obtained (F = 0.63) while PFGE generated 35 pulsotypes (F = 0.71). Simpson's index of diversity for different VNTR loci ranged from 0.59 to 0.92. The combined loci increased the discriminatory index to 0.99 which was comparable with PFGE (D = 0.99). Most of the environmental non-O1/non-O139 strains harbored rtxA, rstR, toxR, and hlyA only, and the virulotype of this serogroup was significantly different (P < .01) from clinical/environmental O1 and environmental O139 strains. In conclusion, the MLVA assay developed in this study was a useful genotyping tool with comparable discriminatory power with PFGE. In addition, the combination of the two approaches can further distinguish the strains from different sources and geographical regions of isolation.
    Matched MeSH terms: Virulence/genetics
  8. Fulltext Molecular characterization of extended-spectrum β-lactamase-producing Klebsiella pneumoniae from a Malaysian hospital
    Mobasseri G, Thong KL, Rajasekaram G, Teh CSJ
    Braz J Microbiol, 2020 Mar;51(1):189-195.
    PMID: 31838661 DOI: 10.1007/s42770-019-00208-w
    Multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae associated with nosocomial infections have caused serious problems in antibiotic management with limited therapeutic choices. This study aimed to determine the genotypic and phenotypic characteristics of K. pneumoniae strains isolated from a tertiary hospital in Malaysia. Ninety-seven clinical K. pneumoniae strains were analyzed for antimicrobial susceptibility, all of which were sensitive to amikacin and colistin (except one strain), while 31.9 % and 27.8 % were MDR and ESBL producers, respectively. PCR and DNA sequencing of the amplicons indicated that the majority of MDR strains (26/27) were positive for blaTEM, followed by blaSHV (24/27), blaCTX-M-1 group (23/27), blaCTX-M-9 group (2/27), and mcr-1 (1/27). Thirty-seven strains were hypervirulent and PCR detection of virulence genes showed 38.1 %, 22.7 %, and 16.5 % of the strains were positive for K1, wabG, and uge genes, respectively. Genotyping by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) showed that these strains were genetically diverse and heterogeneous. Sequence types, ST23, ST22, and ST412 were the predominant genotypes. This is the first report of colistin-resistant K. pneumoniae among clinical strains associated with mcr-1 plasmid in Malaysia. The findings in this study have contributed to the effort in combating the increase in antimicrobial resistance by providing better understanding of genotypic characteristics and resistance mechanisms of the organisms.
    Matched MeSH terms: Virulence/genetics*
  9. Fulltext Virulence Factors and Antibiotic Susceptibility of Staphylococcus aureus Isolates in Ready-to-Eat Foods: Detection of S. aureus Contamination and a High Prevalence of Virulence Genes
    Puah SM, Chua KH, Tan JA
    Int J Environ Res Public Health, 2016 Feb;13(2):199.
    PMID: 26861367 DOI: 10.3390/ijerph13020199
    Staphylococcus aureus is one of the leading causes of food poisoning. Its pathogenicity results from the possession of virulence genes that produce different toxins which result in self-limiting to severe illness often requiring hospitalization. In this study of 200 sushi and sashimi samples, S. aureus contamination was confirmed in 26% of the food samples. The S. aureus isolates were further characterized for virulence genes and antibiotic susceptibility. A high incidence of virulence genes was identified in 96.2% of the isolates and 20 different virulence gene profiles were confirmed. DNA amplification showed that 30.8% (16/52) of the S. aureus carried at least one SE gene which causes staphylococcal food poisoning. The most common enterotoxin gene was seg (11.5%) and the egc cluster was detected in 5.8% of the isolates. A combination of hla and hld was the most prevalent coexistence virulence genes and accounted for 59.6% of all isolates. Antibiotic resistance studies showed tetracycline resistance to be the most common at 28.8% while multi-drug resistance was found to be low at 3.8%. In conclusion, the high rate of S. aureus in the sampled sushi and sashimi indicates the need for food safety guidelines.
    Matched MeSH terms: Virulence/genetics*
  10. Sequence analysis of both genome segments of two very virulent infectious bursal disease virus field isolates with distinct pathogenicity
    Kong LL, Omar AR, Hair-Bejo M, Aini I, Seow HF
    Arch Virol, 2004 Feb;149(2):425-34.
    PMID: 14745606
    The deduced amino acid sequences of segment A and B of two very virulent Infectious bursal disease virus (vvIBDV) isolates, UPM94/273 and UPM97/61 were compared with 25 other IBDV strains. Twenty amino acid residues (8 in VP1, 5 in VP2, 2 in VP3, 4 in VP4, 1 in VP5) that were common to vvIBDV strains were detected. However, UPM94/273 is an exceptional vvIBDV with usual amino acid substitutions. The differences in the divergence of segment A and B indicated that the vvIBDV strains may have been derived from genetic reassortment of a single ancestral virus or both segments have different ability to undergo genetic variation due to their different functional constraints.
    Matched MeSH terms: Virulence/genetics
  11. [Avian influenza: eradication from commercial poultry is still not in sight]
    Landman WJ, Schrier CC
    Tijdschr Diergeneeskd, 2004 Dec 1;129(23):782-96.
    PMID: 15624878
    Avian influenza viruses are highly infectious micro-organisms that primarily affect birds. Nevertheless, they have also been isolated from a number of mammals, including humans. Avian influenza virus can cause large economic losses to the poultry industry because of its high mortality. Although there are pathogenic variants with a low virulence and which generally cause only mild, if any, clinical symptoms, the subtypes H5 and H7 can mutate from a low to a highly virulent (pathogenic) virus and should be taken into consideration in eradication strategies. The primary source of infection for commercial poultry is direct and indirect contact with wild birds, with waterfowl forming a natural reservoir of the virus. Live-poultry markets, exotic birds, and ostriches also play a significant role in the epidemiology of avian influenza. The secondary transmission (i.e., between poultry farms) of avian influenza virus is attributed primarily to fomites and people. Airborne transmission is also important, and the virus can be spread by aerosol in humans. Diagnostic tests detect viral proteins and genes. Virus-specific antibodies can be traced by serological tests, with virus isolation and identification being complementary procedures. The number of outbreaks of avian influenza seems to be increasing - over the last 5 years outbreaks have been reported in Italy, Hong Kong, Chile, the Netherlands, South Korea, Vietnam, Japan, Thailand, Cambodia, Indonesia, Laos, China, Pakistan, United States of America, Canada, South Africa, and Malaysia. Moreover, a growing number of human cases of avian influenza, in some cases fatal, have paralleled the outbreaks in commercial poultry. There is great concern about the possibility that a new virus subtype with pandemic potential could emerge from these outbreaks. From the perspective of human health, it is essential to eradicate the virus from poultry; however, the large number of small-holdings with poultry, the lack of control experience and resources, and the international scale of transmission and infection make rapid control and long-term prevention of recurrence extremely difficult. In the Western world, the renewed interest in free-range housing carries a threat for future outbreaks. The growing ethical objections to the largescale culling of birds require a different approach to the eradication of avian influenza.
    Matched MeSH terms: Virulence/genetics
  12. The FloR master regulator controls flotation, virulence and antibiotic production in Serratia sp. ATCC 39006
    Quintero-Yanes A, Lee CM, Monson R, Salmond G
    Environ Microbiol, 2020 07;22(7):2921-2938.
    PMID: 32352190 DOI: 10.1111/1462-2920.15048
    Serratia sp. ATCC 39006 produces intracellular gas vesicles to enable upward flotation in water columns. It also uses flagellar rotation to swim through liquid and swarm across semi-solid surfaces. Flotation and motility can be co-regulated with production of a β-lactam antibiotic (carbapenem carboxylate) and a linear tripyrrole red antibiotic, prodigiosin. Production of gas vesicles, carbapenem and prodigiosin antibiotics, and motility are controlled by master transcriptional and post-transcriptional regulators, including the SmaI/SmaR-based quorum sensing system and the mRNA binding protein, RsmA. Recently, the ribose operon repressor, RbsR, was also defined as a pleiotropic regulator of flotation and virulence factor elaboration in this strain. Here, we report the discovery of a new global regulator (FloR; a DeoR family transcription factor) that modulates flotation through control of gas vesicle morphogenesis. The floR mutation is highly pleiotropic, down-regulating production of gas vesicles, carbapenem and prodigiosin antibiotics, and infection in Caenorhabditis elegans, but up-regulating flagellar motility. Detailed proteomic analysis using TMT peptide labelling and LC-MS/MS revealed that FloR is a physiological master regulator that operates through subordinate pleiotropic regulators including Rap, RpoS, RsmA, PigU, PstS and PigT.
    Matched MeSH terms: Virulence/genetics*
  13. Antibiotic susceptibility and molecular characterization of Salmonella enterica serovar Paratyphi B isolated from vegetables and processing environment in Malaysia
    Abatcha MG, Effarizah ME, Rusul G
    Int J Food Microbiol, 2019 Feb 02;290:180-183.
    PMID: 30342248 DOI: 10.1016/j.ijfoodmicro.2018.09.021
    Salmonella enterica serovar Paratyphi B (S. Paratyphi B) is a major foodborne pathogen distributed all over the world. However, little is known about the antibiotic resistance, genetic relatedness and virulence profile of S. Paratyphi B isolated from leafy vegetables and the processing environment in Malaysia. In this study, 6 S. Paratyphi B isolates were recovered from different vegetables and drain water of processing areas obtained from fresh food markets in Malaysia. The isolates were characterized by antibiogram, Pulsed-field gel electrophoresis (PFGE) and virulence genes. Antibiotic susceptibility test showed that 3 of the isolates were resistant to the antibiotics. These include S. Paratyphi B SP251 isolate, which was resistant to chloramphenicol, ampicillin, sulfonamides and streptomycin; Isolate SP246 which was resistant to chloramphenicol, sulfonamides and streptomycin and Isolate SP235 showing resistance to nalidixic acid only. PFGE subtyped the 6 S. Paratyphi B isolates into 6 distinct XbaI-pulsotypes, with a wide range of genetic similarity (0.55 to 0.9). The isolates from different sources and fresh food markets location were genetically diverse. Thirteen (tolC, orgA, spaN, prgH, sipB, invA, pefA, sofB, msgA, cdtB, pagC, spiA and spvB) out of the 17 virulence genes tested were found in all of the S. Paratyphi B isolates. Another gene (lpfC), was found only in one isolate (SP051). None of the isolates possessed sifA, sitC and ironN genes. In summary, this study provides unique information on antibiotic resistance, genetic relatedness, and virulotyping of S. Paratyphi B isolated from leafy vegetables and processing environment.
    Matched MeSH terms: Virulence/genetics
  14. Fulltext Ethnicity association of Helicobacter pylori virulence genotype and metronidazole susceptibility
    Alfizah H, Rukman AH, Norazah A, Hamizah R, Ramelah M
    World J Gastroenterol, 2013 Feb 28;19(8):1283-91.
    PMID: 23483193 DOI: 10.3748/wjg.v19.i8.1283
    To characterise the cag pathogenicity island in Helicobacter pylori (H. pylori) isolates by analysing the strains' vacA alleles and metronidazole susceptibilities in light of patient ethnicity and clinical outcome.
    Matched MeSH terms: Virulence/genetics
  15. Molecular characterization of serogrouping and virulence genes of Malaysian Vibrio cholerae isolated from different sources
    Shuan Ju Teh C, Lin Thong K, Tein Ngoi S, Ahmad N, Balakrish Nair G, Ramamurthy T
    J Gen Appl Microbiol, 2009 Dec;55(6):419-25.
    PMID: 20118606
    A pair of primers targeting the hlyA gene for Vibrio cholerae which could distinguish the classical from El Tor biotypes was designed and combined with other specific primers for ompW, rfb complex, and virulence genes such as ctxA, toxR, and tcpI in a multiplex PCR (m-PCR) assay. This m-PCR correctly identified 39 V. cholerae from clinical, water and seafood samples. The efficiency of this multiplex PCR (m-PCR) was compared with conventional biochemical and serogrouping methods. One O139 and 25 O1 V. cholerae strains including 10 environmental strains harbored all virulence-associated genes except 1 clinical strain which only had toxR and hlyA genes. Thirteen environmental strains were classified as non-O1/non-O139 and had the toxR and hlyA genes only. The detection limit of m-PCR was 7 x 10(4) cfu/ml. The m-PCR test was reliable and rapid and reduced the identification time to 4 h.
    Matched MeSH terms: Virulence/genetics
  16. Epstein-Barr virus latent membrane protein-1 oncogene deletions: correlations with malignancy in Epstein-Barr virus--associated lymphoproliferative disorders and malignant lymphomas
    Kingma DW, Weiss WB, Jaffe ES, Kumar S, Frekko K, Raffeld M
    Blood, 1996 Jul 01;88(1):242-51.
    PMID: 8704180
    LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cell lines, nasopharyngeal carcinoma (NPC), a subset of Hodgkin's disease (HD), and in EBV-associated lymphoproliferative disorders (EBV-LPDs). Recently, focused deletions near the 3' end of the LMP-1 gene (del-LMP-1, amino acids 346-355), in a region functionally related to the half-life to the LMP-1 protein, have been reported frequently in human immunodeficiency virus (HIV)-associated HD (100%) and EBV+ Malaysian and Danish peripheral T-cell lymphomas (100%, 61% respectively), but less frequently in cases of HD not associated with HIV (28%, 33%) and infectious mononucleosis (33%). To further investigate the potential relationship of del-LMP-1 to EBV-LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases). The presence of EBV within lymphoid cells was confirmed by EBV EBER1 RNA in situ hybridization or by polymerase chain reaction (PCR) analysis. EBV strain type and LMP-1 deletion status were determined by PCR. EBV strain types segregated into two distinct distributions: HIV+ (9 A; 11 B) and non-HIV (19 A, 0 B), consistent with previous reports. Overall, del-LMP-1 were found in 1 of 5 (20%) Burkitt lymphomas (BL); 17 of 24 (71%) aggressive non-Hodgkin's lymphoma (agg-NHL), and 2 of 10 (20%) reactive lymphoid proliferations. Of the agg-NHLs, del-LMP-1 were present in 4 of 4 PT-ML (100%); 10 of 15 HIV+ ML (67%); and 3 of 5 nonimmunodeficiency malignant lymphoma (ML, 60%). A total of 2 of 7 (28%) sporadic EBV-associated lymphoid hyperplasias contained a del-LMP-1. All del-LMP-1 were identical by DNA sequence analysis. No correlation was identified between the presence of del-LMP-1 and the EBV strain type observed. The high incidence of del-LMP-1 observed in agg-NHLs (71%), in contrast to the relatively low incidence observed in reactive lymphoid proliferations (28%), suggests that the deleted form may be preferentially selected in lymphomatous processes. All posttransplant agg-NHLs contained a del-LMP-1, and a similar frequency of del-LMP-1 was observed in both HIV-associated ML (66%) and nonimmunodeficiency ML (60%), suggesting that impairment of immune function alone is not a requirement for the expansion of malignant cells infected by EBV stains containing the deleted LMP-1 gene.
    Matched MeSH terms: Virulence/genetics
  17. Fulltext Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice
    Yee PTI, Tan SH, Ong KC, Tan KO, Wong KT, Hassan SS, et al.
    Sci Rep, 2019 03 18;9(1):4805.
    PMID: 30886246 DOI: 10.1038/s41598-019-41285-z
    Besides causing mild hand, foot and mouth infections, Enterovirus A71 (EV-A71) is associated with neurological complications and fatality. With concerns about rising EV-A71 virulence, there is an urgency for more effective vaccines. The live attenuated vaccine (LAV) is a more valuable vaccine as it can elicit both humoral and cellular immune responses. A miRNA-based vaccine strain (pIY) carrying let-7a and miR-124a target genes in the EV-A71 genome which has a partial deletion in the 5'NTR (∆11 bp) and G64R mutation (3Dp°l) was designed. The viral RNA copy number and viral titers of the pIY strain were significantly lower in SHSY-5Y cells that expressed both let-7a and miR-124a. Inhibition of the cognate miRNAs expressed in RD and SHSY-5Y cells demonstrated de-repression of viral mRNA translation. A previously constructed multiply mutated strain, MMS and the pIY vaccine strain were assessed in their ability to protect 4-week old mice from hind limb paralysis. The MMS showed higher amounts of IFN-γ ex vivo than the pIY vaccine strain. There was absence of EV-A71 antigen in the skeletal muscles and spinal cord micrographs of mice vaccinated with the MMS and pIY strains. The MMS and pIY strains are promising LAV candidates developed against severe EV-A71 infections.
    Matched MeSH terms: Virulence/genetics*
  18. Infectious cDNA clone of attenuated Langat tick-borne flavivirus (strain E5) and a 3' deletion mutant constructed from it exhibit decreased neuroinvasiveness in immunodeficient mice
    Pletnev AG
    Virology, 2001 Apr 10;282(2):288-300.
    PMID: 11289811
    Forty-five years ago a naturally attenuated tick-borne flavivirus, Langat (LGT) strain TP21, was recovered from ticks in Malaysia. Subsequently, it was tested as a live attenuated vaccine for virulent tick-borne encephalitis viruses. In a large clinical trial its attenuation was confirmed but there was evidence of a low level of residual virulence. Thirty-five years ago further attenuation of LGT TP21 was achieved by multiple passages in eggs to yield mutant E5. To study the genetic determinants of the further attenuation exhibited by E5 and to allow us to manipulate the genome of this virus for the purpose of developing a satisfactory live attenuated tick-borne flavivirus vaccine, we recovered infectious E5 virus from a full-length cDNA clone. The recombinant E5 virus (clone 651) recovered from a full-length infectious cDNA clone was more attenuated in immunodeficient mice than that of its biologically derived E5 parent. Increase in attenuation was associated with three amino acid substitutions, two located in the structural protein E and one in nonstructural protein NS4B. Subsequently an even greater degree of attenuation was achieved by creating a viable 320 nucleotide deletion in the 3'-noncoding region of infectious full-length E5 cDNA. This deletion mutant was not cytopathic in simian Vero cells and it replicated to lower titer than its E5-651 parent. In addition, the E5 3' deletion mutant was less neuroinvasive in SCID mice than its E5-651 parent. Significantly, the deletion mutant proved to be 119,750 times less neuroinvasive in SCID mice than its progenitor, LGT strain TP21. Despite its high level of attenuation, the E5 3' deletion mutant remained highly immunogenic and intraperitoneal (ip) inoculation of 10 PFU induced complete protection in Swiss mice against subsequent challenge with 2000 ip LD50 of the wild-type LGT TP21.
    Matched MeSH terms: Virulence/genetics
  19. 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
  20. 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
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