Nurith Porat

Publications (46)202.57 Total impact

• Article: Baseline epidemiology and genetic structure of Streptococcus pneumoniae serotype 6D in southern Israel prior to the introduction of pneumococcal conjugate vaccines.

  Nurith Porat, Rachel Benisty, Ronit Trefler, Doreen Ozalvo, Noga Givon-Lavi, Ron Dagan
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  ABSTRACT: We characterized Streptococcus pneumoniae serotype 6D (Sp6D) from previously identified Sp6B among Jewish and Bedouin children in southern Israel, during a decade before vaccination. Sp6D constituted 6.7% of the presumed Sp6B. Sp6D strains belonged to 20 sequence types that were differentially distributed among the 2 ethnic groups.
  Journal of clinical microbiology 02/2013; · 4.16 Impact Factor
• Article: Thiol peroxidase is an important component of Streptococcus pneumoniae in oxygenated environments.

  Barak Hajaj, Hasan Yesilkaya, Rachel Benisty, Maayan David, Peter W Andrew, Nurith Porat
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  ABSTRACT: Streptococcus pneumoniae is an aerotolerant Gram-positive bacterium that causes an array of diseases, including pneumonia, otitis media, and meningitis. During aerobic growth, S. pneumoniae produces high levels of H(2)O(2). Since S. pneumoniae lacks catalase, the question of how it controls H(2)O(2) levels is of critical importance. The psa locus encodes an ABC Mn(2+)-permease complex (psaBCA) and a putative thiol peroxidase, tpxD. This study shows that tpxD encodes a functional thiol peroxidase, involved in the adjustment of H(2)O(2) homeostasis in the cell. Kinetic experiments showed that recombinant TpxD removed H(2)O(2) efficiently. However, in vivo experiments revealed that TpxD detoxifies only a fraction of H(2)O(2) generated by the pneumococcus. Mass spectrometry analysis demonstrated that TpxD-cysteine(58) undergoes selective oxidation in vivo, under conditions where H(2)O(2) is formed, confirming the thiol peroxidase activity. TpxD expression and synthesis in vitro were significantly increased in cells grown under aerobic vs. anaerobic conditions. Challenging D39 and TIGR4 with H(2)O(2) resulted in tpxD up-regulation, while psaBCA expression was oppositely affected. However, challenging ΔtpxD-mutants with H(2)O(2) did not affect psaBCA, implying that TpxD is involved in the regulation of the psa operon, in addition to its scavenging activity. Virulence studies demonstrated a notable difference in the survival time of mice infected intranasally with D39 compared to D39ΔtpxD. However, when bacteria were directly administered into the blood, this difference disappeared. The findings of this study suggest that TpxD constitutes a component of the organism's fundamental strategy to fine-tune cellular processes in response to H(2)O(2).
  Infection and immunity 10/2012; · 4.21 Impact Factor
• Article: Clonal Distribution of Common Pneumococcal Serotypes Not Included in the 7-Valent Conjugate Vaccine (PCV7): Marked Differences between Two Ethnic Populations in Southern Israel.

  Nurith Porat, Rachel Benisty, Ronit Trefler, Noga Givon-Lavi, Ron Dagan
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  ABSTRACT: This study aimed to compare the clonal distribution of common pneumococcal strains not included in the 7-valent pneumococcal conjugate vaccine (PCV7) that were isolated from cases of acute otitis media (AOM) and invasive pneumococcal disease (IPD) in two distinct ethnic populations in southern Israel during the decade (1999 to 2008) preceding PCV7 implementation. Isolates recovered from Jewish and Bedouin children <5 years old were characterized by antibiotic resistance and molecular epidemiology using pulsed-field gel electrophoresis and multilocus sequence typing. Of 5,236 AOM and 425 IPD isolates, 43% and 57% were from Jewish and Bedouin children, respectively. PCV7 accounted for 54% and 45% of the AOM and IPD episodes, respectively. Eleven major non-PCV7 serotypes (1, 3, 5, 6A, 7F, 12F, 15B/C, 19A, 21, 33F, and 35B) constituted 31% and 42% of the AOM and IPD episodes, respectively. The clonal distributions of the 11 non-PCV7 serotypes and their antibiotic susceptibilities were significantly different among the two ethnic populations in both the AOM and IPD groups. About half of the AOM and IPD cases resulted from non-PCV7 pneumococci, even before PCV7 implementation. The significant differences between the two ethnic populations suggest that lifestyle and microenvironment are major determinants in the clonal distribution of disease-causing pneumococci. Post-PCV7 surveillance is important in understanding non-PCV7 clonal expansion in the two distinct populations.
  Journal of clinical microbiology 08/2012; 50(11):3472-7. · 4.16 Impact Factor
• Article: The effect of an alternative reduced-dose infant schedule and a second year catch-up schedule with 7-valent pneumococcal conjugate vaccine on pneumococcal carriage: a randomized controlled trial.

  Ron Dagan, Noga Givon-Lavi, Nurith Porat, David Greenberg
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  ABSTRACT: The 7-valent pneumococcal conjugate vaccine (PCV7) was initially licensed for use as 3 infant doses and a booster (3+1). However, 2 infant doses plus a booster schedules only (2+1) are widely used. We compared the effect of these two schedules on pneumococcal carriage in young children. We also assessed the effect of a 2-dose schedule in the second year ("catch-up" schedule; 0+2). Subjects (n=733) were randomized to the 2+1 (4, 6, 12 m), 3+1 (2, 4, 6, 12 m) or 0+2 (12, 18 m) schedules. Blood samples for serotype-specific IgG (SSIgG) determination were obtained at 2, 7, 13, 19 months, and nasopharyngeal+oropharyngeal pneumococcal cultures were obtained at 2, 4, 6, 7, 12, 13, 18, 19, 24, 30 months. After primary infant PCV7 series, SSIgG was significantly lower for four out of seven serotypes in children receiving 2 doses compared to 3 doses, particularly for serotypes 6B and 23F. This was associated with a higher acquisition and prevalence rates of vaccine serotype carriage in the 2-dose group, particularly serotypes 6A and 6B. After the booster dose at 12 months of age, most differences were not significant anymore. A single PCV7 dose at age 12 months in previously unvaccinated subjects ("catch up" schedule) resulted in poor SSIgG concentrations for three out of seven serotypes, resulting in higher acquisition and prevalence rates of vaccine serotypes (grouped) compared to infants receiving a booster dose at 12 months (2+1 and 3+1 groups). Similarly, serotypes 6B and 6A also showed significantly higher carriage rates after a single dose at 12 months. After the second catch-up dose at 18 months, the rates were similar to those in the 2+1 or 3+1 schedules, except for serotype 6A. Three infant doses seem to better protect against PCV7-serotype acquisition and carriage than two. However, after booster, most of these differences disappear. A 2-dose second year catch-up campaign may enhance the reduction of PCV7-serotype spread in the community.
  Vaccine 06/2012; 30(34):5132-40. · 3.77 Impact Factor
• Article: Streptococcus pneumoniae serotypes isolated from the middle ear fluid of Costa Rican children following introduction of the heptavalent pneumococcal conjugate vaccine into a limited population.

  Silvia Guevara, Arturo Abdelnour, Carolina Soley, Nurith Porat, Ron Dagan, Adriano Arguedas
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  ABSTRACT: The heptavalent pneumococcal conjugate vaccine (PCV-7) was introduced in high risk children and into the private market in Costa Rica in 2004 (<5% annual birth cohort). The aim of this study was to compare the Streptococcus pneumoniae serotype (ST) distribution, antibiotic resistance patterns and potential coverage before and after partial introduction of PCV-7. A comparison between the S. pneumoniae isolates obtained and serotyped from the middle ear fluid (MEF) of Costa Rican children with otitis media between years 1999 and 2003 (before PCV-7 usage) and those isolates obtained from 2004 to 2008. A total of 145 and 218 MEF S. pneumoniae were serotyped between years 1999 and 2003 and 2004 and 2008, respectively. Considering a 19F outbreak observed between years 1999 and 2003, the following statistically significant changes in serotype distribution were detected between 1999 and 2003 and 2004 and 2008: ST 3: 4.8-12.8% (P=0.01); ST 11A: 0-4.1% (P=0.01); ST 14: 3.5-21.1% (P<0.001) and ST 19F: 52.4-18.3% (P<0.05). Comparison of the two study periods demonstrated that during 2004 and 2008 a statistically significant decrease in penicillin non-susceptible serotypes (36.2-20.4% [P=0.003]) and a statistically significant increase in trimethoprim-sulfametoxazole resistant serotypes (54.9-68.5%, respectively [P=0.03]) was observed. Potential pneumococcal vaccines coverage between 1999 and 2003 and between 2004 and 2008 were: for PCV-7: 77.2-60.5%, respectively (P=0.001); for the 10-valent conjugated vaccine (PCV-10): 78.6-61.4%, respectively (P=0.0008) and for the 13-valent conjugated vaccine (PCV-13): 84.8-79.3%, respectively (P=0.2). Changes in the serotype distribution and antimicrobial susceptibility of MEF S. pneumoniae have been observed in Costa Rican children with OM. Because of the limited use of PCV-7 during the study period, these changes probably cannot be attributed to PCV-7 use. Between 2004 and 2008, PCV-13 offered the highest potential vaccine coverage.
  Vaccine 04/2012; 30(26):3857-61. · 3.77 Impact Factor
• Article: Prospective epidemiologic surveillance of invasive pneumococcal disease and pneumonia in children in San José, Costa Rica.

  Adriano Arguedas, Arturo Abdelnour, Carolina Soley, Elias Jimenez, Ana Laura Jimenez, Darmendra Ramcharran, Nurith Porat, Ron Dagan, Sharon Gray, Gail L Rodgers
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  ABSTRACT: Streptococcus pneumoniae (SP) is the leading cause of vaccine-preventable death in children <5 years of age, globally. This surveillance determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest radiograph-confirmed pneumonia (CXR+Pn); and SP serotype distribution and antimicrobial susceptibility in children in San José, Costa Rica. This was a 2-year prospective, population-based surveillance conducted in 2007-2009 in children aged 28 days to 36 months presenting to participating healthcare centers. Eligibility criteria for study inclusion were as follows: temperature ≥ 39.0°C within 24h and/or clinical suspicion of IPD or pneumonia. 8801 subjects were enrolled. Median age: 14.5 months. A total of 25 children had invasive pneumococcal disease with S. pneumoniae isolated from nonduplicative cultures (22) or detected solely by PCR and a clinical picture consistent with IPD (3). Sources of positive cultures (some children had >1 positive culture) were: blood (20), pleural fluid (4), and cerebrospinal fluid (3). Of the 3 cases detected solely by PCR, 2 were from cerebrospinal fluid and 1 from pleural fluid. The overall IPD incidence rates for culture-positive only cases for children aged 28 days to <3 years was 33.7/100,000 per year for years 1 and 2 combined. Age stratification of culture-positive only subjects showed a peak during year 1 (106.8/100,000) in children 28 days to <6 months of age group, and in year 2 (45.5/100,000) in children 12 months to <24 months of age group. Most common serotypes were 14 (28.6%), followed by 3, 4, 6A, 19A, and 22F (9.5% each). Of 22 nonduplicative IPD isolates, 42.9% were penicillin- and trimethoprim/sulfamethoxazole nonsusceptible isolates. Consideration of PCR-positive cases increases the incidence of IPD for children aged 28 days to <3 years to 46.0/100,000. Overall incidence of clinical pneumonia and CXR+Pn was 1968/100,000 and 551/100,000, respectively. There is a considerable burden of IPD and pneumonia in children in San José. These epidemiologic data serve as a baseline to evaluate the effectiveness of the incorporation of new conjugate pneumococcal vaccines into the National Immunization Program in Costa Rican children.
  Vaccine 03/2012; 30(13):2342-8. · 3.77 Impact Factor
• Article: Differential occurrence of Streptococcus pneumoniae serotype 11E between asymptomatic carriage and invasive pneumococcal disease isolates reflects a unique model of pathogen microevolution.

  Juan J Calix, Ron Dagan, Stephen I Pelton, Nurith Porat, Moon H Nahm
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  ABSTRACT: Streptococcus pneumoniae is a commensal colonizer of the human nasopharynx (NP) that causes disease after evasion of host defenses and dissemination. Pneumococcal strains expressing the newly identified serotype 11E arise from antigenically similar 11A progenitors by genetic inactivation of the O-acetyltransferase gene wcjE. Each 11E strain contains a distinct mutation to wcjE, suggesting that 11E strains are not transmitted among hosts despite their recovery from multiple patients with pneumococcal disease. We investigated whether the presumed lack of transmission of serotype 11E is consistent with its inability to survive in the NP. More than 400 pneumococcal carriage, middle ear, conjunctiva, and blood isolates, serotyped as 11A by Quellung reaction, were reexamined for reactivity to 11A- and 11E-specific antibodies. We confirmed serotyping of isolates with sequencing of wcjE alleles. Serotype 11E strains were statistically more likely to occur among blood (4 of 15), conjunctiva (1 of 14), or middle ear (2 of 21) isolates than among carriage isolates (2 of 355). All 11E isolates contained unique mutations that putatively decrease wcjE expression. The lack of a circulating 11E clone and the increased occurrence of 11E strains among disease isolates supports the idea that serotype 11E independently arises during infection after initial colonization with a serotype 11A progenitor. Factors encountered in the NP likely contribute to relative rarity of 11E among carriage isolates, whereas selective pressures in deeper tissues possibly promote 11E emergence. These findings illustrate a novel model of microevolution that transpires during the span of a single encounter with serotype 11A, highlighting the adaptability of bacterial pathogens within hosts.
  Clinical Infectious Diseases 03/2012; 54(6):794-9. · 9.15 Impact Factor
• Article: Dynamics of Pneumococcal Acquisition and Carriage in Young Adults during Training in Confined Settings in Israel.

  Hagai Levine, Ran D Balicer, Salman Zarka, Tamar Sela, Vladislav Rozhavski, Daniel Cohen, Raid Kayouf, Ruhama Ambar, Nurith Porat, Ron Dagan
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  ABSTRACT: Outbreaks and sporadic cases of pneumococcal illness occur among young adults in confined settings. Our aim was to characterize pneumococcal acquisition and carriage among healthy young adults in Israel during military training in confined settings. During the years 2007-2008, an observational longitudinal study was conducted in three cohorts of healthy soldiers, during a 7-month basic training period. Epidemiological data, oropharyngeal and nasopharyngeal cultures were sampled on 5 occasions: before and 3, 6, 12 and 24 weeks after start of training. Samples were processed within 2-18 hours. Relatedness of isolates was investigated by capsular typing of all isolates and pulsed-field gel electrophoresis to determine acquisition and transmission. Carriage and acquisition patterns were analyzed and multivariable logistic regression analysis was performed to assess the impact of time on acquisition after mixing, controlling for other covariates. Pneumococci were recovered on 202 of 1872 visits among 742 individuals, including 40 different serotypes. Mean carriage prevalence increased in all visits following training initiation. Acquisition during training was high, as 36.9% of individuals acquired pneumococci at least once during training, and for almost one fourth of the whole population this occurred during the first 6 weeks. Significant clustering was noted. Sharing drinking glass/bottle was found to be a significant and common risk factor for pneumococcal acquisition. Pneumococcal acquisition is highly frequent when young adults live in close contact in confined settings, especially early after mixing.
  PLoS ONE 01/2012; 7(10):e46491. · 4.09 Impact Factor
• Article: Epidemiology of invasive Kingella kingae infections in 2 distinct pediatric populations cohabiting in one geographic area.

  Uri Amit, Ron Dagan, Nurith Porat, Ronit Trefler, Pablo Yagupsky
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  ABSTRACT: The annual incidence of invasive Kingella kingae infection in children younger than 4 years of age was significantly higher in westernized Jews than in indigent Bedouins living side by side in southern Israel (12.21/100,000 and 5.83/100,000, respectively, (P < 0.05). One K. kingae clone was overrepresented among isolates from Jewish children, suggesting that differences in bacterial pathogenicity may contribute to the morbidity excess detected in this population group.
  The Pediatric Infectious Disease Journal 12/2011; 31(4):415-7. · 3.58 Impact Factor
• Article: Distribution, dynamics and antibiotic resistance patterns of Streptococcus pneumoniae serotypes causing acute otitis media in children in southern Israel during the 10 year-period before the introduction of the 7-valent pneumococcal conjugate vaccine.

  Ido Somech, Ron Dagan, Noga Givon-Lavi, Nurith Porat, Simon Raiz, Alberto Leiberman, Mark Puterman, Nehama Peled, David Greenberg, Eugene Leibovitz
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  ABSTRACT: To determine the dynamics of serotype prevalence, potential coverage by pneumococcal conjugate vaccines (PCV) and antibiotic resistance patterns of Streptococcus pneumoniae causing acute otitis media (AOM) in children in southern Israel before PCV7 introduction in the routine immunization program in Israel. All S. pneumoniae isolates from middle ear fluid from children with AOM during 1999-2008 were included. Prospectively collected demographic data on S. pneumoniae serotypes and antibiotic resistance patterns were analyzed. A total of 14,911 tympanocenteses yielded 5281 (35%) S. pneumoniae. Proportion of S. pneumoniae-AOM did not vary significantly (overall 35%; 33% in 2007; 38% in 2002 and 2003). The most frequent serotypes were 19F, 14, 23F and 19A; in both Jewish and Bedouin children; serotypes 6A and 19A contributed 6% and 10%, respectively, of all S. pneumoniae isolates. Serotypes included in PCV7, PCV10 and PCV13 represented 60%, 64%, 85% in Jewish children vs. 49%, 55% and 74%, respectively, in Bedouin children (P < 0.001). Nonsusceptibility to TMP/SMX decreased significantly, in parallel with a significant increase in the nonsusceptibility to erythromycin, clindamycin and in multidrug resistant (MDR) isolates. No changes were recorded in the proportion of S. pneumoniae isolates with penicillin MIC ≥ 1.0 μg/ml. The proportion of penicillin- and erythromycin-nonsusceptible and of MDR serotype 6A and 19A isolates increased significantly in Bedouin children. (1) No significant changes were recorded in the yearly proportions of serotypes 23F, 19F, 19A, 14 and 6A in both ethnic populations; (2) Potential coverage of the 3 PCVs was higher in Jewish children than in Bedouin children; (3) The relatively high coverage of macrolides- and multidrug-resistant S. pneumoniae by PCV13 and lack of increase in penicillin, erythromycin and multidrug nonsusceptibility among non-PCV13 isolates is encouraging.
  Vaccine 06/2011; 29(25):4202-9. · 3.77 Impact Factor
• Article: Streptococcus pneumoniae nasopharyngeal colonization in children in Brasov, Central Romania: high antibiotic resistance and coverage by conjugate vaccines.

  Oana Falup-Pecurariu, Laura Bleotu, Cristina Zavarache, Nechama Peled, Oana Anton, Michaela Robu, Cristian Falup-Pecurariu, Liliana Rogozea, Nurith Porat, David Greenberg, Ron Dagan, Eugene Leibovitz
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  ABSTRACT: We report high colonization rates among 400 healthy infants and children, and moderate (66%) coverage by PCV7 and PCV10, with a superior (80%) PCV13 coverage. Most frequent serotypes were 23F, 6B, 19F, and 14. Resistance to penicillin, ceftriaxone, erythromycin, and trimethoprim/sulfamethoxazole was 83%, 18%, 62%, and 66%, respectively. 67% isolates were multidrug resistant. Pneumococcal conjugate vaccines covered 80% to 93% of multidrug resistant isolates.
  The Pediatric Infectious Disease Journal 01/2011; 30(1):76-8. · 3.58 Impact Factor
• Article: Differential circulation of Streptococcus pneumoniae serotype 6C clones in two Israeli pediatric populations.

  Nurith Porat, In Ho Park, Moon H Nahm, Ron Dagan
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  ABSTRACT: We genotyped Streptococcus pneumoniae serotype 6C (Sp6C) isolates collected from Jewish and Bedouin children in southern Israel during the decade before vaccination. Sp6C constituted 8.2% of the presumed Sp6A isolates. All of the Sp6C clonal clusters were associated with serogroup 6, mainly Sp6A. Different clonal distributions were found in the two subpopulations.
  Journal of clinical microbiology 10/2010; 48(12):4649-51. · 4.16 Impact Factor
• Article: Endogenous H2O2 produced by Streptococcus pneumoniae controls FabF activity.

  Rachel Benisty, Aharon Yehonatan Cohen, Alexandra Feldman, Zvi Cohen, Nurith Porat
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  ABSTRACT: FabF elongation condensing enzyme is a critical factor in determining the spectrum of products produced by the FASII pathway. Its active site contains a critical cysteine-thiol residue, which is a plausible target for oxidation by H2O2. Streptococcus pneumoniae produces exceptionally high levels of H2O2, mainly through the conversion of pyruvate to acetyl-P via pyruvate oxidase (SpxB). We present evidence showing that endogenous H2O2 inhibits FabF activity by specifically oxidizing its active site cysteine-thiol residue. Thiol trapping methods revealed that one of the three FabF cysteines in the wild-type strain was oxidized, whereas in an spxB mutant, defective in H2O2 production, none of the cysteines was oxidized, indicating that the difference in FabF redox state originated from endogenous H2O2. In vitro exposure of the spxB mutant to various H2O2 concentrations further confirmed that only one cysteine residue was susceptible to oxidation. By blocking FabF active site cysteine with cerulenin we show that the oxidized cysteine was the catalytic one. Inhibition of FabF activity by either H2O2 or cerulenin resulted in altered membrane fatty acid composition. We conclude that FabF activity is inhibited by H2O2 produced by S. pneumoniae.
  Biochimica et Biophysica Acta 09/2010; 1801(9):1098-104. · 4.66 Impact Factor
• Article: Control of Streptococcus pneumoniae serotype 5 epidemic of severe pneumonia among young army recruits by mass antibiotic treatment and vaccination.

  Ran D Balicer, Salman Zarka, Hagai Levine, Eyal Klement, Tamar Sela, Nurith Porat, Nachman Ash, Ron Dagan
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  ABSTRACT: During an outbreak of severe pneumonia among new army recruits, an epidemiological investigation combined with repeated nasopharyngeal/oropharyngeal cultures from sick and healthy contacts subjects was conducted. Fifteen pneumonia cases and 19 influenza-like illness cases occurred among 596 recruits over a 4-week period in December 2005. Pneumonia attack rates reached up to 5.5%. A single pneumococcus serotype 5 clone was isolated from blood or sputum cultures in 4 patients and 30/124 (24.1%) contacts. Immunization with 23-valent polysaccharide vaccine supplemented with a 2-dose azithromycin mass treatment rapidly terminated the outbreak. Carriage rates dropped to <1%, 24 and 45 days after intervention.
  Vaccine 08/2010; 28(34):5591-6. · 3.77 Impact Factor
• Article: Validation of factor 6d antiserum for serotyping Streptococcus pneumoniae serotype 6C.

  Michael R Jacobs, Ron Dagan, Saralee Bajaksouzian, Anne R Windau, Nurith Porat
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  ABSTRACT: Factor 6d antiserum reacts with the new Streptococcus pneumoniae serotype 6C. Serogroup 6 isolates, consisting of 49 6A, 42 6B and 98 6C strains from the United States and Israel, serotyped in parallel by PCR and capsular swelling methods, were all identified correctly. The new factor 6d antiserum accurately identifies serotype 6C.
  Journal of clinical microbiology 02/2010; 48(4):1456-7. · 4.16 Impact Factor
• Article: Bacteremia caused by a highly-resistant Streptococcus pneumoniae serotype 19A circulating in a daycare center.

  Dror S Shouval, Nurith Porat, Ron Dagan, Nathan Keller, Efraim Bilavsky, Yoram Sivan, Jacob Amir
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  ABSTRACT: We describe the clinical course of a previously healthy 20-month-old toddler admitted with high fever and leukocytosis. Blood culture grew Streptococcus pneumoniae serotype 19A, belonging to the ST663 clone, highly resistant to penicillin, ceftriaxone, and erythromycin. The same clone with identical antibiogram was isolated from the nasopharynx of another three of the other five healthy children attending the same daycare center as the patient. This case exemplifies the potential problems posed by highly-resistant S. pneumoniae serotype 19A, an emerging pathogen worldwide.
  International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 02/2010; 14 Suppl 3:e253-5. · 2.17 Impact Factor
• Article: Increasing importance of multidrug-resistant serotype 6A Streptococcus pneumoniae clones in acute otitis media in southern Israel.

  Nurith Porat, Uri Amit, Noga Givon-Lavi, Eugene Leibovitz, Ron Dagan
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  ABSTRACT: The major aim of this study was to establish the molecular epidemiology dynamics of Streptococcus pneumoniae serotype 6A in acute otitis media, before the introduction of the 7-valent pneumococcal conjugate vaccine. Acute otitis media in Jewish and Bedouin children <5 years old undergoing tympanocentesis during 1999 to 2006, were studied. Serotype 6A was identified by the Quellung reaction and by polymerase chain reaction (PCR) of the wciN gene, to differentiate between 6A and 6C. Antibiogram and molecular typing by pulsed field gel electrophoresis were performed on all 6A isolates. Multilocus sequence typing was performed on representative isolates of each clone. The 7-valent conjugate vaccine had not yet been licensed in Israel during the study period. Serotype 6A constituted 5.8% (254/4408) of all pneumococcal acute otitis media episodes. The yearly proportion of serotype 6A among the Jewish children showed no distinct trend, whereas among the Bedouin children serotype 6A exhibited a significant increase, from 3.0% in 1999 to 7.6% in 2006. Among the Jewish children a single penicillin-nonsusceptible and erythromycin-resistant clone, ST-473, constituted 73.6% of the strains and dominated throughout the study period. Among the Bedouin children, the proportions of the most common, penicillin-nonsusceptible clone, ST-1988, gradually decreased, from 44.1% in 1999 to 2000 to 21.4% in 2005 to 2006, concurrently with the expansion of a multidrug-resistant clone, ST-457, from 5.9% in 1999 to 2000 to 28.6% in 2005 to 2006. The expansion of multidrug-resistant serotype 6A clone occurred before the introduction of the vaccine. Continued surveillance following vaccine introduction is warranted to further investigate its efficacy on vaccine-related serotypes.
  The Pediatric Infectious Disease Journal 11/2009; 29(2):126-30. · 3.58 Impact Factor
• Article: Pyruvate formate lyase is required for pneumococcal fermentative metabolism and virulence.

  Hasan Yesilkaya, Francesca Spissu, Sandra M Carvalho, Vanessa S Terra, Karen A Homer, Rachel Benisty, Nurith Porat, Ana R Neves, Peter W Andrew
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  ABSTRACT: Knowledge of the in vivo physiology and metabolism of Streptococcus pneumoniae is limited, even though pneumococci rely on efficient acquisition and metabolism of the host nutrients for growth and survival. Because the nutrient-limited, hypoxic host tissues favor mixed-acid fermentation, we studied the role of the pneumococcal pyruvate formate lyase (PFL), a key enzyme in mixed-acid fermentation, which is activated posttranslationally by PFL-activating enzyme (PFL-AE). Mutations were introduced to two putative pfl genes, SPD0235 and SPD0420, and two putative pflA genes, SPD0229 and SPD1774. End-product analysis showed that there was no formate, the main end product of the reaction catalyzed by PFL, produced by mutants defective in SPD0420 and SPD1774, indicating that SPD0420 codes for PFL and SPD1774 for putative PFL-AE. Expression of SPD0420 was elevated in galactose-containing medium in anaerobiosis compared to growth in glucose, and the mutation of SPD0420 resulted in the upregulation of fba and pyk, encoding, respectively, fructose 1,6-bisphosphate aldolase and pyruvate kinase, under the same conditions. In addition, an altered fatty acid composition was detected in SPD0420 and SPD1774 mutants. Mice infected intranasally with the SPD0420 and SPD1774 mutants survived significantly longer than the wild type-infected cohort, and bacteremia developed later in the mutant cohort than in the wild type-infected group. Furthermore, the numbers of CFU of the SPD0420 mutant were lower in the nasopharynx and the lungs after intranasal infection, and fewer numbers of mutant CFU than of wild-type CFU were recovered from blood specimens after intravenous infection. The results demonstrate that there is a direct link between pneumococcal fermentative metabolism and virulence.
  Infection and immunity 09/2009; 77(12):5418-27. · 4.21 Impact Factor
• Article: Dissemination of Kingella kingae in the community and long-term persistence of invasive clones.

  Pablo Yagupsky, Inbal Weiss-Salz, Ronen Fluss, Laurence Freedman, Nehama Peled, Ronit Trefler, Nurith Porat, Ron Dagan
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  ABSTRACT: Although Kingella kingae is being increasingly recognized as an important pediatric pathogen, our current understanding of the transmission of the organism is limited. The dissemination of K. kingae in the community was studied in 2 ethnic groups living side-by-side in Southern Israel. Organisms recovered from oropharyngeal cultures, obtained from healthy young Jewish and Bedouin children during a 12-month period, were typed by pulsed-field gel electrophoresis and compared. Isolates from Bedouin children usually differed from those derived from Jews, confirming the relative social isolation of the 2 populations and the importance of close mingling in the spread of K. kingae. Significant clustering of genotypic clones in households and Bedouin neighborhoods was observed, indicating person-to-person transmission through intimate contact. Organisms detected in the study were identical to historical isolates recovered over the last 15 years from respiratory carriers and patients with bacteremia or skeletal infections. The present study demonstrates that children may be asymptomatically colonized in the respiratory tract by virulent K. kingae clones. The organism is transmitted from child-to-child through intimate contact. Some strains exhibit increased fitness and are maintained in the population for prolonged periods.
  The Pediatric Infectious Disease Journal 09/2009; 28(8):707-10. · 3.58 Impact Factor
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  Available from: PubMed Central

  Article: Streptococcus pneumoniae serotype 3 among Costa Rican children with otitis media: clinical, epidemiological characteristics and antimicrobial resistance patterns.

  Arturo Abdelnour, Carolina Soley, Silvia Guevara, Nurith Porat, Ron Dagan, Adriano Arguedas
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  ABSTRACT: After the introduction of the seven valent-pneumococcal conjugated vaccine into our National Immunization Program, it is important to establish and track local serotype distribution in order to evaluate its impact specially because serotype replacement phenomena has been described.To describe the clinical, epidemiological and antimicrobial resistance patterns of Costa Rican children with otitis media caused by Streptococcus pneumoniae serotype 3. Middle ear fluid samples were obtained from Costa Rican children with otitis media who participated in various antimicrobial clinical trials between 1992 and 2007. Streptococcus pneumoniae was identified according to laboratory standard procedures. Strains were serotyped and antimicrobial susceptibility to penicillin, amoxicillin, cefuroxime, ceftriaxone, azithromycin and levofloxacin was determined by E-test. Throughout 1992-2007 a total of 1919 tympanocentesis were performed in children with otitis media (median age: 19 months) and yielded a total of 1208 middle ear isolates. The most common pathogens were: Streptococcus pneumoniae, 511 isolates (49%); Non-Typable Haemophilus influenzae, 386 isolates (37%); Moraxella catarrahalis, 100 isolates (9.5%); and Streptococcus pyogenes, 54 isolates (5%). Streptococcus pneumoniae serotyping was performed in 346/511 isolates (68%) recovered during years 1999-2006. The most common serotypes were 19F (101/30.0%), 14 (46/13.7%), 3 (34/10.1%), 6B (30/8.9%) and 23F (23/6.8%). Analysis performed per years showed a higher prevalence of serotype 3 Streptococcus pneumoniae during the study period 2004 and 2005. During the entire study period (1999-2006) serotype 3 was most commonly isolated in children older than 24 months (61.2% vs 40.6%;P = 0.05) and showed a lower rate of penicillin non-susceptibility (4.0% vs 18%; P = 0.003). Streptococcus pneumoniae serotype 3 is an important pathogen in Costa Rican children with otitis media, especially in children older than 24 months of age (P = 0.05). Most serotype 3 isolates were susceptible to penicillin, cephalosporins, macrolides and quinolones.
  BMC Pediatrics 09/2009; 9:52. · 1.88 Impact Factor