Displaying publications 461 - 480 of 676 in total

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  1. 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: Ascaris lumbricoides/pathogenicity*
  2. Pathogenic and saprophytic Leptospira species in water and soils from selected urban sites in peninsular Malaysia
    Benacer D, Woh PY, Mohd Zain SN, Amran F, Thong KL
    Microbes Environ, 2013;28(1):135-40.
    PMID: 23363618
    Leptospira species were studied in water and soils from selected urban sites in Malaysia. A total of 151 water (n=121) and soil (n=30) samples were collected from 12 recreational lakes and wet markets. All samples were filtered and inoculated into semi-solid Ellinghausen and McCullough modified by Johnson and Harris (EMJH) media supplemented with additional 5-fluorouracil. The cultures were then incubated at 30°C and observed under a dark field microscope with intervals of 10 days. A PCR assay targeting the rrs gene was used to confirm the genus Leptospira among the isolates. Subsequently, the pathogenic status of the isolates was determined using primer sets G1/G2 and Sapro1/Sapro2, which target the secY and rrs genes, respectively. The isolates were identified at serogroup level using the microscopic agglutination test (MAT) while their genetic diversity was assessed by pulsed field gel electrophoresis (PFGE). Based on dark field microscopy, 23.1% (28/121) water and 23.3% (7/30) soil cultures were positive for Leptospira spp. Of the 35 positive cultures, only 8 were pure and confirmed as Leptospira genus by PCR assay. Two out of 8 isolates were confirmed as pathogenic, 5 were saprophytic and one was intermediate. These 8 isolates were negative for the 25 reference hyperimmune rabbit sera tested in the MAT. PFGE showed that all 8 of these environmental Leptospira spp. were genetically diverse. In conclusion, the presence of pathogenic Leptospira spp. in the urban Malaysian environment may indicate and highlight the importance of water screening, especially in recreational lakes, in order to minimize any chance of Leptospira infection.
    Matched MeSH terms: Leptospira/pathogenicity
  3. Fulltext Knowledge, Attitude, and Practices regarding Leptospirosis among Visitors to a Recreational Forest in Malaysia
    Shafie NJ, Abdul Halim NS, Nor Zalipah M, Mohd Amin NAZ, Syed Esa SM, Md-Nor S, et al.
    Am J Trop Med Hyg, 2021 Jan 18;104(4):1290-1296.
    PMID: 33534768 DOI: 10.4269/ajtmh.20-0306
    Leptospirosis is a zoonotic disease and a worldwide public health problem that affects mainly high-risk groups. Characterizing knowledge, attitude, and practice (KAP) among high-risk groups is important to develop appropriate prevention programs. Here, we performed a cross-sectional study among 300 visitors of a recreational forest in Malaysia to examine leptospirosis KAP and demographics. These variables were integrated to create knowledge and practice scores for each respondent. All respondents had heard about leptospirosis, and 87% of them correctly identified it as a disease. The majority of respondents had high knowledge (63%), positive attitude, and good practice (68%) toward prevention of the disease. However, there were gaps in knowledge, with 78% of the respondents indicating eating without washing hands as the major cause of leptospirosis transmission. Our final model identified that higher knowledge score was associated with higher practice score. Our results indicate that it is important to increase knowledge, especially on transmission routes of leptospirosis, among visitors in recreational areas. Moreover, more attention needs to be paid to promote good practice habits among visitors, targeting those at higher risk of being infected by leptospirosis to prevent potential outbreaks in the recreational areas.
    Matched MeSH terms: Leptospira/pathogenicity
  4. A PROspective study on the Usage patterns of Doripenem in the Asia-Pacific region (PROUD study)
    Mustafa M, Chan WM, Lee C, Harijanto E, Loo CM, Van Kinh N, et al.
    Int J Antimicrob Agents, 2014 Apr;43(4):353-60.
    PMID: 24636429 DOI: 10.1016/j.ijantimicag.2014.01.017
    Doripenem is approved in the Asia-Pacific (APAC) region for treating nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP), complicated intra-abdominal infections (cIAIs) and complicated urinary tract infections (cUTIs). Clinical usage of doripenem (500mg intravenously, infused over 1h or 4h every 8h for 5-14 days) in APAC was evaluated in a prospective, open-label, non-comparative, multicentre study of inpatients (≥18 years) with NP, VAP, cIAI or cUTI. A total of 216 [intention-to-treat (ITT)] patients received doripenem: 53 NP (24.5%); 77 VAP (35.6%); 67 cIAI (31.0%); and 19 cUTI (8.8%). Doripenem MIC90 values for Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae were 32, 32, 0.094 and 0.64μg/mL, respectively. Doripenem was used most commonly as monotherapy (86.6%) and as second-line therapy (62.0%). The clinical cure rate in clinically evaluable patients was 86.7% at the end of therapy (EOT) and 87.1% at test of cure (TOC) (7-14 days after EOT). In the ITT population, overall clinical cure rates were 66.2% at EOT and 56.5% at TOC. The median duration of hospital stay, intensive care unit (ICU) stay and mechanical ventilation was 20, 12 and 10 days, respectively. Of 146 discharged patients, 7 were re-admitted within 28 days of EOT; 1 VAP patient was re-admitted to the ICU. The all-cause mortality rate was 22.7% (49/216). The most common treatment-related adverse events were diarrhoea (1.4%) and vomiting (1.4%). Doripenem is a viable option for treating APAC patients with NP, VAP, cIAI or cUTI. [ClinicalTrials.gov: NCT 00986102].
    Matched MeSH terms: Escherichia coli/pathogenicity; Klebsiella pneumoniae/pathogenicity; Pseudomonas aeruginosa/pathogenicity; Acinetobacter baumannii/pathogenicity
  5. Fulltext Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model
    Kong C, Yehye WA, Abd Rahman N, Tan MW, Nathan S
    BMC Complement Altern Med, 2014;14:4.
    PMID: 24393217 DOI: 10.1186/1472-6882-14-4
    The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.
    Matched MeSH terms: Staphylococcus aureus/pathogenicity; Methicillin-Resistant Staphylococcus aureus/pathogenicity
  6. Clinical and pathological manifestations of human henipavirus infection
    Wong KT, Tan CT
    Curr. Top. Microbiol. Immunol., 2012;359:95-104.
    PMID: 22427144 DOI: 10.1007/82_2012_205
    The clinicopathological features of human Nipah virus and Hendra virus infections appear to be similar. The clinical manifestations may be mild, but if severe, includes acute encephalitic and pulmonary syndromes with a high mortality. The pathological features in human acute henipavirus infections comprise vasculopathy (vasculitis, endothelial multinucleated syncytia, thrombosis), microinfarcts and parenchymal cell infection in the central nervous system, lung, kidney and other major organs. Viral inclusions, antigens, nucleocapsids and RNA are readily demonstrated in blood vessel wall and numerous types of parenchymal cells. Relapsing henipavirus encephalitis is a rare complication reported in less than 10% of survivors of the acute infection and appears to be distinct from the acute encephalitic syndrome. Pathological evidence suggests viral recrudescence confined to the central nervous system as the cause.
    Matched MeSH terms: Hendra Virus/pathogenicity; Nipah Virus/pathogenicity
  7. Infections of Blastocystis hominis and microsporidia in cancer patients: are they opportunistic?
    Chandramathi S, Suresh K, Anita ZB, Kuppusamy UR
    Trans R Soc Trop Med Hyg, 2012 Apr;106(4):267-9.
    PMID: 22340948 DOI: 10.1016/j.trstmh.2011.12.008
    Chemotherapy can cause immunosuppression, which may trigger latent intestinal parasitic infections in stools to emerge. This study investigated whether intestinal parasites can emerge as opportunistic infections in breast and colorectal cancer patients (n=46 and n=15, respectively) undergoing chemotherapy treatment. Breast cancer patients were receiving a 5-fluorouracil/epirubicin/cyclophosphamide (FEC) regimen (6 chemotherapy cycles), and colorectal cancer patients were receiving either an oxaliplatin/5-fluorouracil/folinic acid (FOLFOX) regimen (12 cycles) or a 5-fluorouracil/folinic acid (Mayo) regimen (6 cycles). Patients had Blastocystis hominis and microsporidia infections that were only present during the intermediate chemotherapy cycles. Thus, cancer patients undergoing chemotherapy should be screened repeatedly for intestinal parasites, namely B. hominis and microsporidia, as they may reduce the efficacy of chemotherapy treatments.
    Matched MeSH terms: Microsporidia/pathogenicity*; Blastocystis hominis/pathogenicity*
  8. Fulltext Genotypic variations of virulent genes in Enterococcus faecium and Enterococcus faecalis isolated from three hospitals in Malaysia
    Al-Talib H, Zuraina N, Kamarudin B, Yean CY
    Adv Clin Exp Med, 2015 Jan-Feb;24(1):121-7.
    PMID: 25923096 DOI: 10.17219/acem/38162
    The genus Enterococcus is of increasing significance as a cause of nosocomial infections, and this trend is exacerbated by the development of antibiotic resistance.
    Matched MeSH terms: Enterococcus faecalis/pathogenicity*; Enterococcus faecium/pathogenicity*
  9. Emerging and re-emerging epidemic encephalitis: a tale of two viruses
    Wong KT
    Neuropathol. Appl. Neurobiol., 2000 Aug;26(4):313-8.
    PMID: 10931364
    Two major epidemics of viral encephalitis occurred in Asia in 1997 and 1998. The first was a re-emergence of neurovirulent strains of enterovirus 71, which caused severe encephalomyelitis in children in Malaysia, Taiwan and Japan, on a background of hand, foot and mouth disease. Necropsy studies of patients who died of enterovirus 71 infection showed severe perivascular cuffing, parenchymal inflammation and neuronophagia in the spinal cord, brainstem and diencephalon, and in focal areas in the cerebellum and cerebrum. Although no viral inclusions were detected, immunohistochemistry showed viral antigen in the neuronal cytoplasm. Inflammation was often more extensive than neuronal infection, suggesting that other factors, in addition to direct viral cytolysis, may be involved in tissue damage. The second epidemic of viral encephalitis was the result of a novel paramyxovirus called Nipah, which mainly involved pig handlers in Malaysia and Singapore. Pathological evidence suggested that the endothelium of small blood vessels in the central nervous system was particularly susceptible to infection. This led to disseminated endothelial damage and syncytium formation, vasculitis, thrombosis, ischaemia and microinfarction. However, there was also evidence of neuronal infection by the virus and this may also have contributed to the neurological dysfunction in Nipah encephalitis. Some patients who seemed to recover from the acute symptoms have been re-admitted with clinical findings suggestive of relapsing encephalitis. As these two epidemics indicate, the emergence and re-emergence of viral encephalitides continue to pose considerable challenges to the neuropathologist, in establishing the diagnosis and unravelling the pathogenesis of the neurological disease.
    Matched MeSH terms: Enterovirus/pathogenicity; Paramyxovirinae/pathogenicity
  10. Fulltext Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit
    Abdul-Aziz MH, Abd Rahman AN, Mat-Nor MB, Sulaiman H, Wallis SC, Lipman J, et al.
    Antimicrob Agents Chemother, 2016 01;60(1):206-14.
    PMID: 26482304 DOI: 10.1128/AAC.01543-15
    Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.
    Matched MeSH terms: Pseudomonas aeruginosa/pathogenicity; Acinetobacter baumannii/pathogenicity
  11. Differential attenuation of Marek's disease virus-induced tumours and late-Marek's disease virus-induced immunosuppression
    Faiz NM, Cortes AL, Guy JS, Reddy SM, Gimeno IM
    J Gen Virol, 2018 07;99(7):927-936.
    PMID: 29767614 DOI: 10.1099/jgv.0.001076
    Marek's disease virus (MDV) is a herpesvirus that induces lymphoma and a variety of non-neoplastic syndromes in chickens. Furthermore, very virulent plus (vv+) MDVs induce a form of immunosuppression (late-MDV-IS) that might involve both neoplastic and non-neoplastic mechanisms. The objective of this study was to evaluate whether the attenuation of MDV-induced tumours and late-MDV-IS occurs simultaneously or can be dissociated. The immunosuppressive ability of three viruses derived from vv+ MDV strain 686 (wild-type 686, the somewhat attenuated molecular clone 686-BAC, and the nononcogenic molecular clone lacking the two copies of the oncogene meq 686-BACΔMEQ) was evaluated. Late-MDV-IS was evaluated indirectly by assessing the negative effect of MDV strains on the protection conferred by infectious laryngotracheitis (ILT) vaccines. Our results showed that the ability to induce late-MDV-IS was attenuated before the ability to induce tumours. Strain 686 induced both tumours and late-MDV-IS, 686-BAC induced tumours but did not induce late-MDV-IS and 686-BACΔMEQ did not induce either tumours or late-MDV-IS. Further comparison of strains 686 and 686-BAC revealed that strain 686 reduced the humoral immune responses to ILTV (1132 vs 2167) more severely, showed higher levels of meq transcripts (2.1E+09 vs 4.98E+8) and higher expression of MDV microRNAs (mdv1-miR-M4-5p and mdv1-miR-M2-3p) in the spleen, and further reduced the percentage of CD45+-MHC-I+splenocytes (13 vs32 %) compared to molecular clone 686-BAC. This study suggests that the immunosuppressive ability of MDV might follow a continuous spectrum and only the most virulent MDVs can overcome a certain threshold level and induce clinical MDV-IS in the ILT model.
    Matched MeSH terms: Herpesvirus 1, Gallid/pathogenicity; Herpesvirus 2, Gallid/pathogenicity
  12. Fulltext Leptospira interrogans  and Leptospira kirschneri are the dominant Leptospira species causing human leptospirosis in Central Malaysia
    Philip N, Bahtiar Affendy N, Ramli SNA, Arif M, Raja P, Nagandran E, et al.
    PLoS Negl Trop Dis, 2020 Mar;14(3):e0008197.
    PMID: 32203511 DOI: 10.1371/journal.pntd.0008197
    BACKGROUND: Leptospirosis, commonly known as rat-urine disease, is a global but endemic zoonotic disease in the tropics. Despite the historical report of leptospirosis in Malaysia, the information on human-infecting species is limited. Determining the circulating species is important to understand its epidemiology, thereby to strategize appropriate control measures through public health interventions, diagnostics, therapeutics and vaccine development.

    METHODOLOGY/PRINCIPLE FINDINGS: We investigated the human-infecting Leptospira species in blood and serum samples collected from clinically suspected leptospirosis patients admitted to three tertiary care hospitals in Malaysia. From a total of 165 patients, 92 (56%) were confirmed cases of leptospirosis through Microscopic Agglutination Test (MAT) (n = 43; 47%), Polymerase Chain Reaction (PCR) (n = 63; 68%) or both MAT and PCR (n = 14; 15%). The infecting Leptospira spp., determined by partial 16S rDNA (rrs) gene sequencing revealed two pathogenic species namely Leptospira interrogans (n = 44, 70%) and Leptospira kirschneri (n = 17, 27%) and one intermediate species Leptospira wolffii (n = 2, 3%). Multilocus sequence typing (MLST) identified an isolate of L. interrogans as a novel sequence type (ST 265), suggesting that this human-infecting strain has a unique genetic profile different from similar species isolated from rodents so far.

    CONCLUSIONS/SIGNIFICANCE: Leptospira interrogans and Leptospira kirschneri were identified as the dominant Leptospira species causing human leptospirosis in Central Malaysia. The existence of novel clinically important ST 265 (infecting human), that is different from rodent L. interrogans strains cautions reservoir(s) of these Leptospira lineages are yet to be identified.

    Matched MeSH terms: Leptospira/pathogenicity; Leptospira interrogans/pathogenicity
  13. Fulltext Burkholderia pseudomallei kills Caenorhabditis elegans through virulence mechanisms distinct from intestinal lumen colonization
    Ooi SK, Lim TY, Lee SH, Nathan S
    Virulence, 2012 Oct 01;3(6):485-96.
    PMID: 23076282 DOI: 10.4161/viru.21808
    The nematode Caenorhabditis elegans is hypersusceptible to Burkholderia pseudomallei infection. However, the virulence mechanisms underlying rapid lethality of C. elegans upon B. pseudomallei infection remain poorly defined. To probe the host-pathogen interaction, we constructed GFP-tagged B. pseudomallei and followed bacterial accumulation within the C. elegans intestinal lumen. Contrary to slow-killing by most bacterial pathogens, B. pseudomallei caused fairly limited intestinal lumen colonization throughout the period of observation. Using grinder-defective mutant worms that allow the entry of intact bacteria also did not result in full intestinal lumen colonization. In addition, we observed a significant decline in C. elegans defecation and pharyngeal pumping rates upon B. pseudomallei infection. The decline in defecation rates ruled out the contribution of defecation to the limited B. pseudomallei colonization. We also demonstrated that the limited intestinal lumen colonization was not attributed to slowed host feeding as bacterial loads did not change significantly when feeding was stimulated by exogenous serotonin. Both these observations confirm that B. pseudomallei is a poor colonizer of the C. elegans intestine. To explore the possibility of toxin-mediated killing, we examined the transcription of the C. elegans ABC transporter gene, pgp-5, upon B. pseudomallei infection of the ppgp-5::gfp reporter strain. Expression of pgp-5 was highly induced, notably in the pharynx and intestine, compared with Escherichia coli-fed worms, suggesting that the host actively thwarted the pathogenic assaults during infection. Collectively, our findings propose that B. pseudomallei specifically and continuously secretes toxins to overcome C. elegans immune responses.
    Matched MeSH terms: Escherichia coli/pathogenicity; Burkholderia pseudomallei/pathogenicity*
  14. Fulltext Molecular identification of human hookworm infections in economically disadvantaged communities in Peninsular Malaysia
    Ngui R, Ching LS, Kai TT, Roslan MA, Lim YA
    Am J Trop Med Hyg, 2012 May;86(5):837-42.
    PMID: 22556084 DOI: 10.4269/ajtmh.2012.11-0446
    Species identification of human hookworm infections among eight communities in rural areas of Peninsular Malaysia was determined during 2009-2011. Fecal samples were examined by microscopy and subsequently, the internal transcribed spacer 2 and 28S ribosomal RNA region of Necator americanus and Ancylostoma spp. were sequenced. Overall, 9.1% (58 of 634) were identified positive by microscopy for hookworm infection, and 47 (81.0%) of 58 were successfully amplified and sequenced. Sequence comparison found that N. americanus (87.2%) was the most predominant hookworm identified, followed by Ancylostoma ceylanicum (23.4%). No A. duodenale infection was detected in this study. Detection of A. ceylanicum in humans highlighted the zoonotic transmission among humans living near dogs. Thus, implementation of effective control measures for hookworm infections in future should seriously consider this zoonotic implication.
    Matched MeSH terms: Ancylostoma/pathogenicity; Necator americanus/pathogenicity
  15. Fulltext Isolation and Characterization of an Atypical Metschnikowia sp. Strain from the Skin Scraping of a Dermatitis Patient
    Kuan CS, Ismail R, Kwan Z, Yew SM, Yeo SK, Chan CL, et al.
    PLoS One, 2016;11(6):e0156119.
    PMID: 27280438 DOI: 10.1371/journal.pone.0156119
    A yeast-like organism was isolated from the skin scraping sample of a stasis dermatitis patient in the Mycology Unit Department of Medical Microbiology, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The isolate produced no pigment and was not identifiable using chromogenic agar and API 20C AUX. The fungus was identified as Metschnikowia sp. strain UM 1034, which is close to that of Metschnikowia drosophilae based on ITS- and D1/D2 domain-based phylogenetic analysis. However, the physiology of the strain was not associated to M. drosophilae. This pathogen exhibited low sensitivity to all tested azoles, echinocandins, 5-flucytosine and amphotericin B. This study provided insight into Metschnikowia sp. strain UM 1034 phenotype profiles using a Biolog phenotypic microarray (PM). The isolate utilized 373 nutrients of 760 nutrient sources and could adapt to a broad range of osmotic and pH environments. To our knowledge, this is the first report of the isolation of Metschnikowia non-pulcherrima sp. from skin scraping, revealing this rare yeast species as a potential human pathogen that may be misidentified as Candida sp. using conventional methods. Metschnikowia sp. strain UM 1034 can survive in flexible and diverse environments with a generalist lifestyle.
    Matched MeSH terms: Metschnikowia/pathogenicity*
  16. Genotypic characterization of Malaysian human isolates of Streptococcus pneumoniae from carriage and clinical sources
    Shakrin NN, Masri SN, Taib NM, Nordin SA, Jamal F, Desa MN
    Comp Immunol Microbiol Infect Dis, 2014 Dec;37(5-6):347-54.
    PMID: 25467035 DOI: 10.1016/j.cimid.2014.10.005
    This study characterized carriage and clinical pneumococcal isolates for serotypes, penicillin susceptibility, virulence genes and restriction fragment length polymorphism (RFLP) pattern of penicillin binding protein (PBP) genes. DNA fingerprint of isolates was generated by BOX-PCR. Majority of serotypes were 23F followed by 19F, 19A and 6A. Twenty-four percent of isolates were penicillin non-susceptible (PNSP). All of the targeted virulence genes were detected in all isolates with the exception of pili; 20.6% (n=22) for PI-1 and 14.0% (n=15) for PI-2. Of the 13 isolates which carried both PI-1 and PI-2, 10 were of clinical origin. Digested pbp-DNA produced three PBP-RFLP profiles for pbp1a (A1 to A3), six profiles for pbp2b (B1 to B6) and seven for pbp2x (X1 to X7) mostly in PNSPs. Based on BOX-PCR analysis, the majority of isolates were genetically diverse with a small number of potentially related isolates carrying pili genes. No obvious genotypic association was observed pertaining to carriage and clinical origin of isolates.
    Matched MeSH terms: Streptococcus pneumoniae/pathogenicity*
  17. Fulltext The West Nile virus-like flavivirus Koutango is highly virulent in mice due to delayed viral clearance and the induction of a poor neutralizing antibody response
    Prow NA, Setoh YX, Biron RM, Sester DP, Kim KS, Hobson-Peters J, et al.
    J Virol, 2014 Sep 1;88(17):9947-62.
    PMID: 24942584 DOI: 10.1128/JVI.01304-14
    The mosquito-borne West Nile virus (WNV) is responsible for outbreaks of viral encephalitis in humans, horses, and birds, with particularly virulent strains causing recent outbreaks of disease in eastern Europe, the Middle East, North America, and Australia. Previous studies have phylogenetically separated WNV strains into two main genetic lineages (I and II) containing virulent strains associated with neurological disease. Several WNV-like strains clustering outside these lineages have been identified and form an additional five proposed lineages. However, little is known about whether these strains have the potential to induce disease. In a comparative analysis with the highly virulent lineage I American strain (WNVNY99), the low-pathogenicity lineage II strain (B956), a benign Australian strain, Kunjin (WNVKUN), the African WNV-like Koutango virus (WNVKOU), and a WNV-like isolate from Sarawak, Malaysia (WNVSarawak), were assessed for neuroinvasive properties in a murine model and for their replication kinetics in vitro. While WNVNY99 replicated to the highest levels in vitro, in vivo mouse challenge revealed that WNVKOU was more virulent, with a shorter time to onset of neurological disease and higher morbidity. Histological analysis of WNVKOU- and WNVNY99-infected brain and spinal cords demonstrated more prominent meningoencephalitis and the presence of viral antigen in WNVKOU-infected mice. Enhanced virulence of WNVKOU also was associated with poor viral clearance in the periphery (sera and spleen), a skewed innate immune response, and poor neutralizing antibody development. These data demonstrate, for the first time, potent neuroinvasive and neurovirulent properties of a WNV-like virus outside lineages I and II.
    Matched MeSH terms: Encephalitis Viruses, Japanese/pathogenicity*
  18. Pathogenicity and phenotypic analysis of sopB, sopD and pipD virulence factors in Salmonella enterica serovar typhimurium and Salmonella enterica serovar Agona
    Khoo CH, Sim JH, Salleh NA, Cheah YK
    Antonie Van Leeuwenhoek, 2015 Jan;107(1):23-37.
    PMID: 25312847 DOI: 10.1007/s10482-014-0300-7
    Salmonella is an important food-borne pathogen causing disease in humans and animals worldwide. Salmonellosis may be caused by any one of over 2,500 serovars of Salmonella. Nonetheless, Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Agona are the second most prevalent serovars isolated from humans and livestock products respectively. Limited knowledge is available about the virulence mechanisms responsible for diarrheal disease caused by them. To investigate the contribution of sopB, sopD and pipD as virulence factors in intracellular infections and the uniqueness of these bacteria becoming far more prevalent than other serovars, the infection model of Caenorhabditis elegans and phenotypic microarray were used to characterize their mutants. The strains containing the mutation in sopB, sopD and pipD genes were constructed by using latest site-specific group II intron mutagenesis approach to reveal the pathogenicity of the virulence factors. Overall, we observed that the mutations in sopB, sopD and pipD genes of both serovars did not exhibit significant decrease in virulence towards the nematode. This may indicate that these virulence effectors may not be universal virulence factors involved in conserved innate immunity. There are significant phenotypic differences amongst strains carrying sopB, sopD and pipD gene mutations via the analysis of biochemical profiles of the bacteria. Interestingly, mutant strains displayed different susceptibility to chemical stressors from several distinct pharmacological and structural classes when compared to its isogenic parental strains. These metabolic and chemosensitivity assays also revealed multiple roles of Salmonella virulence factors in nutrient metabolism and antibiotic resistance.
    Matched MeSH terms: Salmonella enterica/pathogenicity*
  19. Immunoinformatics study on highly expressed Mycobacterium tuberculosis genes during infection
    Nguyen Thi le T, Sarmiento ME, Calero R, Camacho F, Reyes F, Hossain MM, et al.
    Tuberculosis (Edinb), 2014 Sep;94(5):475-81.
    PMID: 25034135 DOI: 10.1016/j.tube.2014.06.004
    The most important targets for vaccine development are the proteins that are highly expressed by the microorganisms during infection in-vivo. A number of Mycobacterium tuberculosis (Mtb) proteins are also reported to be expressed in-vivo at different phases of infection. In the present study, we analyzed multiple published databases of gene expression profiles of Mtb in-vivo at different phases of infection in animals and humans and selected 38 proteins that are highly expressed in the active, latent and reactivation phases. We predicted T- and B-cell epitopes from the selected proteins using HLAPred for T-cell epitope prediction and BCEPred combined with ABCPred for B-cell epitope prediction. For each selected proteins, regions containing both T- and B-cell epitopes were identified which might be considered as important candidates for vaccine design against tuberculosis.
    Matched MeSH terms: Mycobacterium tuberculosis/pathogenicity
  20. Occurrence of Enterococcus species with virulence markers in an urban flow-influenced tropical recreational beach
    Ahmad A, Dada AC, Usup G, Heng LY
    Mar Pollut Bull, 2014 May 15;82(1-2):26-38.
    PMID: 24725825 DOI: 10.1016/j.marpolbul.2014.03.028
    Median enterococci counts of beach water samples gradually increased at statistically significant levels (χ2: 26.53, df: 4; p<0.0001) with increasing proximity to river influx. The difference in proportion of antibiotic resistant enterococci in beach water and river water samples was statistically significant (p<0.05) for the tested antibiotics with river isolates generally presenting higher resistance frequencies. Virulence genes cyl, esp, gelE and asa were detected at varying frequencies (7.32%, 21.95%, 100% and 63.41% respectively) among river isolates. On the other hand, the prevalence of these genes was lower (0%, 20%, 67.27% and 41.82% respectively) among beach water isolates. Multi-Locus-Sequence-Typing analysis of Enterococcus faecalis presented four sequence types (ST) one of which shared six out of seven tested loci with ST6, a member of the clonal complex of multi-drug resistant strains associated with hospital outbreaks.
    Matched MeSH terms: Enterococcus/pathogenicity
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