1887

Abstract

Penicillin-non-susceptible (PNSP) were first detected in the 1960s, and are now common worldwide, predominantly through the international spread of a limited number of strains. Extant PNSP are characterized by mosaic , and genes generated by interspecies recombinations, with the extent of these alterations determining the range and concentrations of β-lactams to which the genotype is non-susceptible. The complexity of the genetics underlying these phenotypes has been the subject of both molecular microbiology and genome-wide association and epistasis analyses. Such studies can aid our understanding of PNSP evolution and help improve the already highly-performing bioinformatic methods capable of identifying PNSP from genomic surveillance data.

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2019-10-01
2019-11-22
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References

  1. Arason VA, Kristinsson KG, Sigurdsson JA, Stefánsdóttir G, Mölstad S et al. Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. BMJ 1996;313:387–391 [CrossRef]
    [Google Scholar]
  2. Guillemot D, Carbon C, Balkau B, Geslin P, Lecoeur H et al. Low dosage and long treatment duration of β-lactam: risk factors for carriage of penicillin-resistant Streptococcus pneumoniae. JAMA 1998;279:365–370 [CrossRef]
    [Google Scholar]
  3. Melander E, Mölstad S, Persson K, Hansson HB, Söderström M et al. Previous antibiotic consumption and other risk factors for carriage of penicillin-resistant Streptococcus pneumoniae in children. Eur J Clin Microbiol Infect Dis 1998;17:834–838 [CrossRef]
    [Google Scholar]
  4. Regev-Yochay G, Raz M, Shainberg B, Dagan R, Varon M et al. Independent risk factors for carriage of penicillin-non-susceptible Streptococcus pneumoniae. Scand J Infect Dis 2003;35:219–222 [CrossRef]
    [Google Scholar]
  5. Nasrin D, Collignon PJ, Roberts L, Wilson EJ, Pilotto LS et al. Effect of beta lactam antibiotic use in children on pneumococcal resistance to penicillin: prospective cohort study. BMJ 2002;324:28 [CrossRef]
    [Google Scholar]
  6. Lipsitch M. Measuring and interpreting associations between antibiotic use and penicillin resistance in Streptococcus pneumoniae. Clin Infect Dis 2001;32:1044–1054 [CrossRef]
    [Google Scholar]
  7. Goossens H, Ferech M, Vander Stichele R, Elseviers M. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. The Lancet 2005;365:579–587 [CrossRef]
    [Google Scholar]
  8. Croucher NJ, Løchen A, Bentley SD. Pneumococcal vaccines: host interactions, population dynamics, and design principles. Annu Rev Microbiol 2018;72:521–549 [CrossRef]
    [Google Scholar]
  9. Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis 2010;201:32–41 [CrossRef]
    [Google Scholar]
  10. Casey JR, Adlowitz DG, Pichichero ME. New patterns in the otopathogens causing acute otitis media six to eight years after introduction of pneumococcal conjugate vaccine. Pediatr Infect Dis J 2010;29:304–309 [CrossRef]
    [Google Scholar]
  11. Gonzales R, Malone DC, Maselli JH, Sande MA. Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect Dis 2001;33:757–762 [CrossRef]
    [Google Scholar]
  12. Vergison A, Dagan R, Arguedas A, Bonhoeffer J, Cohen R et al. Otitis media and its consequences: beyond the earache. Lancet Infect Dis 2010;10:195–203 [CrossRef]
    [Google Scholar]
  13. Tedijanto C, Olesen SW, Grad YH, Lipsitch M. Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora. Proc Natl Acad Sci USA 2018;115:E11988–E11995 [CrossRef]
    [Google Scholar]
  14. Arason VA, Sigurdsson JA, Erlendsdottir H, Gudmundsson S, Kristinsson KG. The role of antimicrobial use in the epidemiology of resistant pneumococci: a 10-year follow up. Microb Drug Resist 2006;12:169–176 [CrossRef]
    [Google Scholar]
  15. Mölstad S, Erntell M, Hanberger H, Melander E, Norman C et al. Sustained reduction of antibiotic use and low bacterial resistance: 10-year follow-up of the Swedish Strama programme. Lancet Infect Dis 2008;8:125–132 [CrossRef]
    [Google Scholar]
  16. Belongia EA, Sullivan BJ, Chyou PH, Madagame E, Reed KD et al. A community intervention trial to promote judicious antibiotic use and reduce penicillin-resistant Streptococcus pneumoniae carriage in children. Pediatrics 2001;108:575–583 [CrossRef]
    [Google Scholar]
  17. Barkai G, Greenberg D, Givon-Lavi N, Dreifuss E, Vardy D et al. Community prescribing and resistant Streptococcus pneumoniae. Emerg Infect Dis 2005;11:829–837 [CrossRef]
    [Google Scholar]
  18. Centers for Disease Control and Prevention Antibiotic Resistance Threats in the United States, 2013 Atlanta, GA: Centers for Disease Control and Prevention; 2013
    [Google Scholar]
  19. Harboe ZB, Thomsen RW, Riis A, Valentiner-Branth P, Christensen JJ et al. Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study. PLoS Med 2009;6:e1000081 [CrossRef]
    [Google Scholar]
  20. Tleyjeh IM, Tlaygeh HM, Hejal R, Montori VM, Baddour LM. The impact of penicillin resistance on short-term mortality in hospitalized adults with pneumococcal pneumonia: a systematic review and meta-analysis. Clin Infect Dis 2006;42:788–797 [CrossRef]
    [Google Scholar]
  21. Navarro-Torné A, Dias JG, Hruba F, Lopalco PL, Pastore-Celentano L et al. Risk factors for death from invasive pneumococcal disease, Europe, 2010. Emerg Infect Dis 2015;21:417–425 [CrossRef]
    [Google Scholar]
  22. Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European economic area in 2015: a population-level modelling analysis. Lancet Infect Dis 2019;19:56–66 [CrossRef]
    [Google Scholar]
  23. Weinstein MP, Klugman KP, Jones RN. Rationale for revised penicillin susceptibility breakpoints versus Streptococcus pneumoniae: coping with antimicrobial susceptibility in an era of resistance. Clin Infect Dis 2009;48:1596–1600 [CrossRef]
    [Google Scholar]
  24. Kislak JW, Razavi LM, Daly AK, Finland M. Susceptibility of pneumococci to nine antibiotics. Am J Med Sci 1965;250:261–268 [CrossRef]
    [Google Scholar]
  25. Jacobs MR, Mithal Y, Robins-Browne RM, Gaspar MN, Koornhof HJ. Antimicrobial susceptibility testing of pneumococci: determination of Kirby-Bauer breakpoints for penicillin G, erythromycin, clindamycin, tetracycline, chloramphenicol, and rifampin. Antimicrob Agents Chemother 1979;16:190–197 [CrossRef]
    [Google Scholar]
  26. Zighelboim S, Tomasz A. Penicillin-binding proteins of multiply antibiotic-resistant South African strains of Streptococcus pneumoniae. Antimicrob Agents Chemother 1980;17:434–442 [CrossRef]
    [Google Scholar]
  27. Dowson CG, Hutchison A, Brannigan JA, George RC, Hansman D et al. Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Proc Natl Acad Sci USA 1989;86:8842–8846 [CrossRef]
    [Google Scholar]
  28. Laible G, Spratt BG, Hakenbeck R. Interspecies recombinational events during the evolution of altered PBP 2x genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Mol Microbiol 1991;5:1993–2002 [CrossRef]
    [Google Scholar]
  29. Dowson CG, Coffey TJ, Kell C, Whiley RA. Evolution of penicillin resistance in Streptococcus pneumoniae; the role of Streptococcus mitis in the formation of a low affinity PBP2B in S. pneumoniae. Mol Microbiol 1993;9:635–643 [CrossRef]
    [Google Scholar]
  30. Dowson CG, Barcus V, King S, Pickerill P, Whatmore A et al. Horizontal gene transfer and the evolution of resistance and virulence determinants in Streptococcus. J Appl Microbiol 1997;83:42S–51S [CrossRef]
    [Google Scholar]
  31. Zapun A, Contreras-Martel C, Vernet T. Penicillin-binding proteins and β-lactam resistance. FEMS Microbiol Rev 2008;32:361–385 [CrossRef]
    [Google Scholar]
  32. du Plessis M, Bingen E, Klugman KP. Analysis of penicillin-binding protein genes of clinical isolates of Streptococcus pneumoniae with reduced susceptibility to amoxicillin. Antimicrob Agents Chemother 2002;46:2349–2357 [CrossRef]
    [Google Scholar]
  33. Muñoz R, Dowson CG, Daniels M, Coffey TJ, Martin C et al. Genetics of resistance to third-generation cephalosporins in clinical isolates of Streptococcus pneumoniae. Mol Microbiol 1992;6:2461–2465 [CrossRef]
    [Google Scholar]
  34. Philippe J, Gallet B, Morlot C, Denapaite D, Hakenbeck R et al. Mechanism of β-lactam action in Streptococcus pneumoniae: the piperacillin paradox. Antimicrob Agents Chemother 2015;59:609–621 [CrossRef]
    [Google Scholar]
  35. Grebe T, Hakenbeck R. Penicillin-binding proteins 2B and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of beta-lactam antibiotics. Antimicrob Agents Chemother 1996;40:829–834 [CrossRef]
    [Google Scholar]
  36. Smith AM, Klugman KP. Alterations in MurM, a cell wall muropeptide branching enzyme, increase high-level penicillin and cephalosporin resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother 2001;45:2393–2396 [CrossRef]
    [Google Scholar]
  37. Filipe SR, Severina E, Tomasz A. The murMN operon: a functional link between antibiotic resistance and antibiotic tolerance in Streptococcus pneumoniae. Proc Natl Acad Sci USA 2002;99:1550–1555 [CrossRef]
    [Google Scholar]
  38. Coffey TJ, Dowson CG, Daniels M, Zhou J, Martin C et al. Horizontal transfer of multiple penicillin-binding protein genes, and capsular biosynthetic genes, in natural populations of Streptococcus pneumoniae. Mol Microbiol 1991;5:2255–2260 [CrossRef]
    [Google Scholar]
  39. Chewapreecha C, Marttinen P, Croucher NJ, Salter SJ, Harris SR et al. Comprehensive identification of single nucleotide polymorphisms associated with beta-lactam resistance within pneumococcal mosaic genes. PLoS Genet 2014;10:e1004547 [CrossRef]
    [Google Scholar]
  40. Li Y, Metcalf BJ, Chochua S, Li Z, Gertz RE et al. Penicillin-binding protein transpeptidase signatures for tracking and predicting β-lactam resistance levels in Streptococcus pneumoniae. mBio 2016;7:e00756-16 [CrossRef]
    [Google Scholar]
  41. Skwark MJ, Croucher NJ, Puranen S, Chewapreecha C, Pesonen M et al. Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis. PLoS Genet 2017;13:e1006508 [CrossRef]
    [Google Scholar]
  42. Puranen S, Pesonen M, Pensar J, Xu YY, Lees JA et al. SuperDCA for genome-wide epistasis analysis. Microb Genomics 2018;4:e000184 [CrossRef]
    [Google Scholar]
  43. Pensar J, Puranen S, Arnold B, MacAlasdair N, Kuronen J et al. Genome-wide epistasis and co-selection study using mutual information. Nucleic Acids Res 2019;47:e112 [CrossRef]
    [Google Scholar]
  44. Albarracín Orio AG, Piñas GE, Cortes PR, Cian MB, Echenique J. Compensatory evolution of pbp mutations restores the fitness cost imposed by β-lactam resistance in Streptococcus pneumoniae. PLoS Pathog 2011;7:e1002000 [CrossRef]
    [Google Scholar]
  45. Croucher NJ, Finkelstein JA, Pelton SI, Mitchell PK, Lee GM et al. Population genomics of post-vaccine changes in pneumococcal epidemiology. Nat Genet 2013;45:656–663 [CrossRef]
    [Google Scholar]
  46. McGee L, McDougal L, Zhou J, Spratt BG, Tenover FC et al. Nomenclature of major antimicrobial-resistant clones of Streptococcus pneumoniae defined by the pneumococcal molecular epidemiology network. J Clin Microbiol 2001;39:2565–2571 [CrossRef]
    [Google Scholar]
  47. Klugman KP. The successful clone: the vector of dissemination of resistance in Streptococcus pneumoniae. J Antimicrob Chemother 2002;50 (Suppl. 2):1–5 [CrossRef]
    [Google Scholar]
  48. Gladstone RA, Lo SW, Lees JA, Croucher NJ, van Tonder AJ et al. International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact. EBioMedicine 2019;43:338–346 [CrossRef]
    [Google Scholar]
  49. Lees JA, Harris SR, Tonkin-Hill G, Gladstone RA, Lo SW et al. Fast and flexible bacterial genomic epidemiology with PopPUNK. Genome Res 2019;29:304–316 [CrossRef]
    [Google Scholar]
  50. Croucher NJ, Harris SR, Fraser C, Quail MA, Burton J et al. Rapid pneumococcal evolution in response to clinical interventions. Science 2011;331:430–434 [CrossRef]
    [Google Scholar]
  51. Croucher NJ, Chewapreecha C, Hanage WP, Harris SR, McGee L et al. Evidence for soft selective sweeps in the evolution of pneumococcal multidrug resistance and vaccine escape. Genome Biol Evol 2014;6:1589–1602 [CrossRef]
    [Google Scholar]
  52. Croucher NJ, Hanage WP, Harris SR, McGee L, van der Linden M et al. Variable recombination dynamics during the emergence, transmission and 'disarming' of a multidrug-resistant pneumococcal clone. BMC Biol 2014;12:49 [CrossRef]
    [Google Scholar]
  53. Wyres KL, Lambertsen LM, Croucher NJ, McGee L, von Gottberg A et al. The multidrug-resistant PMEN1 pneumococcus is a paradigm for genetic success. Genome Biol 2012;13:R103 [CrossRef]
    [Google Scholar]
  54. Mostowy R, Croucher NJ, Hanage WP, Harris SR, Bentley S et al. Heterogeneity in the frequency and characteristics of homologous recombination in pneumococcal evolution. PLoS Genet 2014;10:e1004300 [CrossRef]
    [Google Scholar]
  55. Chewapreecha C, Harris SR, Croucher NJ, Turner C, Marttinen P et al. Dense genomic sampling identifies highways of pneumococcal recombination. Nat Genet 2014;46:305–309 [CrossRef]
    [Google Scholar]
  56. Trzciński K, Thompson CM, Lipsitch M. Single-step capsular transformation and acquisition of penicillin resistance in Streptococcus pneumoniae. J Bacteriol 2004;186:3447–3452 [CrossRef]
    [Google Scholar]
  57. Hausdorff WP, Feikin DR, Klugman KP. Epidemiological differences among pneumococcal serotypes. Lancet Infect Dis 2005;5:83–93 [CrossRef]
    [Google Scholar]
  58. Kyaw MH, Lynfield R, Schaffner W, Craig AS, Hadler J et al. Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae. N Engl J Med 2006;354:1455–1463 [CrossRef]
    [Google Scholar]
  59. Wroe PC, Lee GM, Finkelstein JA, Pelton SI, Hanage WP et al. Pneumococcal carriage and antibiotic resistance in young children before 13-valent conjugate vaccine. Pediatr Infect Dis J 2012;31:249–254 [CrossRef]
    [Google Scholar]
  60. Moore MR, Hyde TB, Hennessy TW, Parks DJ, Reasonover AL et al. Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska. J Infect Dis 2004;190:2031–2038 [CrossRef]
    [Google Scholar]
  61. Reinert R, Jacobs MR, Kaplan SL. Pneumococcal disease caused by serotype 19A: review of the literature and implications for future vaccine development. Vaccine 2010;28:4249–4259 [CrossRef]
    [Google Scholar]
  62. Kim L, McGee L, Tomczyk S, Beall B. Biological and epidemiological features of antibiotic-resistant Streptococcus pneumoniae in pre- and post-conjugate vaccine eras: A United States perspective. Clin Microbiol Rev 2016;29:525–552 [CrossRef]
    [Google Scholar]
  63. Horácio AN, Silva-Costa C, Lopes E, Ramirez M, Melo-Cristino J et al. Conjugate vaccine serotypes persist as major causes of non-invasive pneumococcal pneumonia in Portugal despite declines in serotypes 3 and 19A (2012-2015). PLoS One 2018;13:e0206912 [CrossRef]
    [Google Scholar]
  64. Kandasamy R, Voysey M, Collins S, Berbers G, Robinson H et al. Persistent circulation of vaccine serotypes and serotype replacement after five years of UK infant immunisation with PCV13. J Infect Dis 2019;jiz178 [CrossRef]
    [Google Scholar]
  65. Lo SW, Gladstone RA, van Tonder AJ, Lees JA, du Plessis M et al. Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study. Lancet Infect Dis 2019;19:759–769 [CrossRef]
    [Google Scholar]
  66. Càmara J, Cubero M, Martín-Galiano AJ, García E, Grau I et al. Evolution of the β-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain. J Antimicrob Chemother 2018;73:2941–2951 [CrossRef]
    [Google Scholar]
  67. Chochua S, Metcalf BJ, Li Z, Walker H, Tran T et al. Invasive serotype 35B pneumococci including an expanding serotype switch lineage, United States, 2015-2016. Emerg Infect Dis 2017;23:922–930 [CrossRef]
    [Google Scholar]
  68. Ouldali N, Levy C, Varon E, Bonacorsi S, Béchet S et al. Incidence of paediatric pneumococcal meningitis and emergence of new serotypes: a time-series analysis of a 16-year French national survey. Lancet Infect Dis 2018;18:983–991 [CrossRef]
    [Google Scholar]
  69. Kapatai G, Sheppard CL, Al-Shahib A, Litt DJ, Underwood AP et al. Whole genome sequencing of Streptococcus pneumoniae: development, evaluation and verification of targets for serogroup and serotype prediction using an automated pipeline. PeerJ 2016;4:e2477 [CrossRef]
    [Google Scholar]
  70. Epping L, van Tonder AJ, Gladstone RA, Bentley SD, Page AJ et al. SeroBA: rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data. Microb Genomics 2018;4:mgen.0.000186
    [Google Scholar]
  71. Metcalf BJ, Chochua S, Gertz RE, Li Z, Walker H et al. Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States. Clin Microbiol Infect 2016;22:1002.e1–1002.e8 [CrossRef]
    [Google Scholar]
  72. Metcalf BJ, Gertz RE, Gladstone RA, Walker H, Sherwood LK et al. Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA. Clin Microbiol Infect 2016;22:60.e9–60.e29 [CrossRef]
    [Google Scholar]
  73. Li Y, Metcalf BJ, Chochua S, Li Z, Gertz RE et al. Validation of β-lactam minimum inhibitory concentration predictions for pneumococcal isolates with newly encountered penicillin binding protein (PBP) sequences. BMC Genomics 2017;18:621 [CrossRef]
    [Google Scholar]
  74. Corander J, Fraser C, Gutmann MU, Arnold B, Hanage WP et al. Frequency-dependent selection in vaccine-associated pneumococcal population dynamics. Nat Ecol Evol 2017;1:1950–1960 [CrossRef]
    [Google Scholar]
  75. Hussain M, Melegaro A, Pebody RG, George R, Edmunds WJ et al. A longitudinal household study of Streptococcus pneumoniae nasopharyngeal carriage in a UK setting. Epidemiol Infect 2005;133:891–898 [CrossRef]
    [Google Scholar]
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