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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*
Fulltext RNA-seq data of Ganoderma boninense at axenic culture condition and under in planta pathogen-oil palm (Elaeis guineensis Jacq.) interaction

Wong MY, Govender NT, Ong CS

BMC Res Notes, 2019 Sep 24;12(1):631.
PMID: 31551084 DOI: 10.1186/s13104-019-4652-y

OBJECTIVE: Basal stem rot disease causes severe economic losses to oil palm production in South-east Asia and little is known on the pathogenicity of the pathogen, the basidiomyceteous Ganoderma boninense. Our data presented here aims to identify both the house-keeping and pathogenicity genes of G. boninense using Illumina sequencing reads.
DESCRIPTION: The hemibiotroph G. boninense establishes via root contact during early stage of colonization and subsequently kills the host tissue as the disease progresses. Information on the pathogenicity factors/genes that causes BSR remain poorly understood. In addition, the molecular expressions corresponding to G. boninense growth and pathogenicity are not reported. Here, six transcriptome datasets of G. boninense from two contrasting conditions (three biological replicates per condition) are presented. The first datasets, collected from a 7-day-old axenic condition provide an insight onto genes responsible for sustenance, growth and development of G. boninense while datasets of the infecting G. boninense collected from oil palm-G. boninense pathosystem (in planta condition) at 1 month post-inoculation offer a comprehensive avenue to understand G. boninense pathogenesis and infection especially in regard to molecular mechanisms and pathways. Raw sequences deposited in Sequence Read Archive (SRA) are available at NCBI SRA portal with PRJNA514399, bioproject ID.

Matched MeSH terms: Virulence/genetics
Fulltext Comparative genome sequencing and analyses of Mycobacterium cosmeticum reveal potential for biodesulfization of gasoline

Wee WY, Dutta A, Jayaraj J, Choo SW

PLoS One, 2019;14(4):e0214663.
PMID: 30964891 DOI: 10.1371/journal.pone.0214663

Mycobacterium cosmeticum is a nontuberculous Mycobacterium recovered from different water sources including household potable water and water collected at nail salon. Individual cases of this bacterium have been reported to be associated with gastrointestinal tract infections. Here we present the first whole-genome study and comparative analysis of two new clinically-derived Mycobacterium sp. UM_RHS (referred as UM_RHS after this) and Mycobacterium sp. UM_NYF (referred as UM_NYF after this) isolated from patients in Indonesia and Malaysia respectively to have a better understanding of the biological characteristic of these isolates. Both strains are likely Mycobacterium cosmeticum as supported by the evidence from molecular phylogenetic, comparative genomic and Average Nucleotide Identity (ANI) analyses. We found the presence of a considerably large number of putative virulence genes in the genomes of UM_RHS and UM_NYF. Interestingly, we also found a horizontally transferred genomic island carrying a putative dsz operon proposing that they may have potential to perform biodesulfization of dibenzothiophene (DBT) that may be effective in cost reduction and air pollution during fuel combustion. This comparative study may provide new insights into M. cosmeticum and serve as an important reference for future functional studies of this bacterial species.

Matched MeSH terms: Virulence/genetics
Possible virulence factors involved in bacteraemia caused by Aeromonas hydrophila

Vadivelu J, Puthucheary SD, Phipps M, Chee YW

J Med Microbiol, 1995 Mar;42(3):171-4.
PMID: 7884797

Eighteen strains of Aeromonas hydrophila from patients with bacteraemia were investigated for possible virulence factors. Cytotoxin and haemolysin were produced by all strains, whereas cholera toxin-like factor was produced by 33% of strains only. Enterotoxin production was not detected. Haemagglutination of guinea-pig, fowl and rabbit erythrocytes was demonstrated by 83%, 67% and 61% of strains, respectively. Fucose- and mannose-sensitive haemagglutinins were predominant. None of the strains agglutinated sheep erythrocytes. Extrachromosomal DNA was detected in 17 strains, 16 of which had a plasmid (3.6-5.1 MDa), the majority being between 4.6 and 5.1 MDa.

Matched MeSH terms: Virulence/genetics
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
Fulltext Evolutionary study of Yersinia genomes deciphers emergence of human pathogenic species

Tan SY, Tan IK, Tan MF, Dutta A, Choo SW

Sci Rep, 2016 10 31;6:36116.
PMID: 27796355 DOI: 10.1038/srep36116

On record, there are 17 species in the Yersinia genus, of which three are known to be pathogenic to human. While the chromosomal and pYV (or pCD1) plasmid-borne virulence genes as well as pathogenesis of these three species are well studied, their genomic evolution is poorly understood. Our study aims to predict the key evolutionary events that led to the emergence of pathogenic Yersinia species by analyzing gene gain-and-loss, virulence genes, and "Clustered regularly-interspaced short palindromic repeats". Our results suggest that the most recent ancestor shared by the human pathogenic Yersinia was most probably an environmental species that had adapted to the human body. This might have led to ecological specialization that diverged Yersinia into ecotypes and distinct lineages based on differential gene gain-and-loss in different niches. Our data also suggest that Y. pseudotuberculosis group might be the donor of the ail virulence gene to Y. enterocolitica. Hence, we postulate that evolution of human pathogenic Yersinia might not be totally in parallel, but instead, there were lateral gene transfer events. Furthermore, the presence of virulence genes seems to be important for the positive selection of virulence plasmid. Our studies provide better insights into the evolutionary biology of these bacteria.

Matched MeSH terms: Virulence/genetics
Fulltext YersiniaBase: a genomic resource and analysis platform for comparative analysis of Yersinia

Tan SY, Dutta A, Jakubovics NS, Ang MY, Siow CC, Mutha NV, et al.

BMC Bioinformatics, 2015;16:9.
PMID: 25591325 DOI: 10.1186/s12859-014-0422-y

Yersinia is a Gram-negative bacteria that includes serious pathogens such as the Yersinia pestis, which causes plague, Yersinia pseudotuberculosis, Yersinia enterocolitica. The remaining species are generally considered non-pathogenic to humans, although there is evidence that at least some of these species can cause occasional infections using distinct mechanisms from the more pathogenic species. With the advances in sequencing technologies, many genomes of Yersinia have been sequenced. However, there is currently no specialized platform to hold the rapidly-growing Yersinia genomic data and to provide analysis tools particularly for comparative analyses, which are required to provide improved insights into their biology, evolution and pathogenicity.

Matched MeSH terms: Virulence/genetics*
Distribution of Helicobacter pylori cagA, cagE and vacA in different ethnic groups in Kuala Lumpur, Malaysia

Tan HJ, Rizal AM, Rosmadi MY, Goh KL

J Gastroenterol Hepatol, 2005 Apr;20(4):589-94.
PMID: 15836708

There is a geographic variation in Helicobacter pylori (HP) genotypes and virulence factors. Cytotoxin associated genes A (cagA) and E (cagE), and certain vacuolating cytotoxin (vacA) genotypes are associated with peptic ulcer disease (PUD). There is also a different prevalence of PUD among different ethnic groups in Malaysia. The present study compared the distribution of vacA alleles and cagA and cagE status in three ethnic groups residing in Kuala Lumpur, Malaysia, and their association with clinical outcome.

Matched MeSH terms: Virulence/genetics
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
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
Differential expression of cytokine genes in THP-1-derived macrophages infected with mild and virulence strains of Shigella flexneri 2a

Shabani NRM, Mokhtar M, Leow CH, Lean QY, Chuah C, Singh KKB, et al.

Infect Genet Evol, 2020 11;85:104532.
PMID: 32911076 DOI: 10.1016/j.meegid.2020.104532

Shigella is an intracellular bacterial pathogen that causes bacterial dysentery called shigellosis. The assessment of pro- and anti-inflammatory mediators produced by immune cells against this bacteria are vital in identifying the effectiveness of the immune reaction in protecting the host. In Malaysia, Shigella is ranked as the third most common bacteria causing diarrheal disease among children below 5 years old. In the present study, we aim to examine the differential cytokine gene expressions of macrophages in response to two types of clinical strains of Shigella flexneri 2a (S. flexneri 2a) isolated from patients admitted in Hospital Universiti Sains Malaysia, Kelantan, Malaysia. THP-1-derived macrophages, as the model of human macrophages, were infected separately with S. flexneri 2a mild (SH062) and virulence (SH057) strains for 6, 12, and 24 h, respectively. The gene expression level of inflammatory mediators was identified using real-time quantitative polymerase chain reaction (RT-qPCR). The production of nitric oxide (NO) by the macrophages was measured by using a commercialized NO assay kit. The ability of macrophages to kill the intracellular bacteria was assessed by intracellular killing assay. Induction of tumor necrosis factor-alpha (TNFα), interleukin (IL)-1β, IL-6, IL-12, inducible NO synthase (iNOS), and NO, confirmed the pro-inflammatory reaction of the THP-1-derived macrophages in response to S. flexneri 2a, especially against the SH507 strain. The SH057 also induced a marked increase in the expression levels of the anti-inflammatory cytokine mRNAs at 12 h and 24 h post-infection. In the intracellular killing assay, both strains showed less viable, indicating the generation of pro-inflammatory cytokines in the presence of iNOS and NO was crucial in the stimulation of macrophages for the host defense against shigellosis. Transcription analysis of THP-1-derived macrophages in this study identifies differentially expressed cytokine genes that correlated with the virulence factor of S. flexneri 2a.

Matched MeSH terms: Virulence/genetics*
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*
Fulltext Molecular characterization of putative virulence determinants in Burkholderia pseudomallei

Puah SM, Puthucheary SD, Wang JT, Pan YJ, Chua KH

ScientificWorldJournal, 2014;2014:590803.
PMID: 25215325 DOI: 10.1155/2014/590803

The Gram-negative saprophyte Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease which is endemic in Southeast Asia and northern Australia. This bacterium possesses many virulence factors which are thought to contribute to its survival and pathogenicity. Using a virulent clinical isolate of B. pseudomallei and an attenuated strain of the same B. pseudomallei isolate, 6 genes BPSL2033, BP1026B_I2784, BP1026B_I2780, BURPS1106A_A0094, BURPS1106A_1131, and BURPS1710A_1419 were identified earlier by PCR-based subtractive hybridization. These genes were extensively characterized at the molecular level, together with an additional gene BPSL3147 that had been identified by other investigators. Through a reverse genetic approach, single-gene knockout mutants were successfully constructed by using site-specific insertion mutagenesis and were confirmed by PCR. BPSL2033::Km and BURPS1710A_1419::Km mutants showed reduced rates of survival inside macrophage RAW 264.7 cells and also low levels of virulence in the nematode infection model. BPSL2033::Km demonstrated weak statistical significance (P = 0.049) at 8 hours after infection in macrophage infection study but this was not seen in BURPS1710A_1419::Km. Nevertheless, complemented strains of both genes were able to partially restore the gene defects in both in vitro and in vivo studies, thus suggesting that they individually play a minor role in the virulence of B. pseudomallei.

Matched MeSH terms: Virulence/genetics*
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*
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
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
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
Fulltext Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas

Ortiz RH, Leon DA, Estevez HO, Martin A, Herrera JL, Romo LF, et al.

Clin Exp Immunol, 2009 Aug;157(2):271-81.
PMID: 19604267 DOI: 10.1111/j.1365-2249.2009.03941.x

Buruli ulcer (BU) is the third most common mycobacterial disease in immunocompetent hosts. BU is caused by Mycobacterium ulcerans, which produces skin ulcers and necrosis at the site of infection. The principal virulence factor of M. ulcerans is a polyketide-derived macrolide named mycolactone, which has cytotoxic and immunosuppressive activities. We determined the severity of inflammation, histopathology and bacillary loads in the subcutaneous footpad tissue of BALB/c mice infected with 11 different M. ulcerans isolates from diverse geographical areas. Strains from Africa (Benin, Ghana, Ivory Coast) induced the highest inflammation, necrosis and bacillary loads, whereas the strains collected from Australia, Asia (Japan, Malaysia, New Guinea), Europe (France) and America (Mexico) induced mild inflammation. Subsequently, animals were infected with the strain that exhibited the highest (Benin) or lowest (Mexico) level of virulence in order to analyse the local immune response generated. The Mexican strain, which does not produce mycolactone, induced a predominantly T helper type 1 (Th1) cytokine profile with constant high expression of the anti-microbial peptides beta defensins 3 and 4, in co-existence with low expression of the anti-inflammatory cytokines interleukin (IL)-10, IL-4 and transforming growth factor (TGF)-beta. The highly virulent strain from Benin which produces mycolactone A/B induced the opposite pattern. Thus, different local immune responses were found depending on the infecting M. ulcerans strain.

Matched MeSH terms: Virulence/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*
The emergence of the multi-species NIP1 effector in Rhynchosporium was accompanied by high rates of gene duplications and losses

Mohd-Assaad N, McDonald BA, Croll D

Environ Microbiol, 2019 08;21(8):2677-2695.
PMID: 30838748 DOI: 10.1111/1462-2920.14583

Plant pathogens secrete effector proteins to manipulate the host and facilitate infection. Cognate hosts trigger strong defence responses upon detection of these effectors. Consequently, pathogens and hosts undergo rapid coevolutionary arms races driven by adaptive evolution of effectors and receptors. Because of their high rate of turnover, most effectors are thought to be species-specific and the evolutionary trajectories are poorly understood. Here, we investigate the necrosis-inducing protein 1 (NIP1) effector in the multihost pathogen genus Rhynchosporium. We retraced the evolutionary history of the NIP1 locus using whole-genome assemblies of 146 strains covering four closely related species. NIP1 orthologues were present in all species but the locus consistently segregated presence-absence polymorphisms suggesting long-term balancing selection. We also identified previously unknown paralogues of NIP1 that were shared among multiple species and showed substantial copy-number variation within R. commune. The NIP1A paralogue was under significant positive selection suggesting that NIP1A is the dominant effector variant coevolving with host immune receptors. Consistent with this prediction, we found that copy number variation at NIP1A had a stronger effect on virulence than NIP1B. Our analyses unravelled the origins and diversification mechanisms of a pathogen effector family shedding light on how pathogens gain adaptive genetic variation.

Matched MeSH terms: Virulence/genetics

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