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Volume 169, Issue 11

Comparative genomics of clinical isolates reveals genetic diversity which correlates with colonization and persistence Open Access

Abstract

is a Gram-negative emerging opportunistic pathogen often present in people with respiratory diseases such as cystic fibrosis (CF). People with CF (pwCF) experience lifelong polymicrobial infections of the respiratory mucosa. Our prior work showed that promotes persistence of in mouse respiratory infections. As is typical for environmental opportunistic pathogens, has a large genome and a high degree of genetic diversity. In this study, we evaluated the genomic content of combining short and long read sequencing to construct nearly complete genomes of 10 clinical isolates. The genomes of these isolates were then compared with all publicly available genome assemblies, and each isolate was then evaluated for colonization/persistence , both alone and in coinfection with . We found that while the overall genome size and GC content were fairly consistent between strains, there was considerable variability in both genome structure and gene content. Similarly, there was significant variability in colonization and persistence in experimental mouse respiratory infections in the presence or absence of . Ultimately, this study gives us a greater understanding of the genomic diversity of clinical isolates, and how this genomic diversity relates to both interactions with other pulmonary pathogens and to host disease progression. Identifying the molecular determinants of infection with can facilitate development of novel antimicrobial strategies for a highly drug-resistant pathogen.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): adherence , comparative genomics , polymicrobial infection , Pseudomonas aeruginosa and Stenotrophomonas maltophilia
Funding
This study was supported by the:
  • National Institute of Diabetes and Digestive and Kidney Diseases (Award P30DK072482)
    • Principle Award Recipient: NotApplicable
  • National Heart, Lung, and Blood Institute (Award T32HL134640)
    • Principle Award Recipient: W.Edward Swords
  • Cystic Fibrosis Foundation (Award RDP R15RO)
    • Principle Award Recipient: MelissaS. McDaniel
  • Cystic Fibrosis Foundation (Award CFF SWORDS20G0)
    • Principle Award Recipient: W.Edward Swords
  • Cystic Fibrosis Foundation (Award CFF SWORDS1810)
    • Principle Award Recipient: W.Edward Swords
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
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2023-11-09
2024-05-19
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References

  1. Brooke JS. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev 2012; 25:2–41 [View Article] [PubMed]
     [Google Scholar]
  2. Denton M, Todd NJ, Kerr KG, Hawkey PM, Littlewood JM. Molecular epidemiology of Stenotrophomonas maltophilia isolated from clinical specimens from patients with cystic fibrosis and associated environmental samples. J Clin Microbiol 1998; 36:1953–1958 [View Article] [PubMed]
     [Google Scholar]
  3. Rabin HR, Surette MG. The cystic fibrosis airway microbiome. Curr Opin Pulm Med 2012; 18:622–627 [View Article] [PubMed]
     [Google Scholar]
  4. Sibley CD, Parkins MD, Rabin HR, Surette MG. The relevance of the polymicrobial nature of airway infection in the acute and chronic management of patients with cystic fibrosis. Curr Opin Investig Drugs 2009; 10:787–794 [PubMed]
     [Google Scholar]
  5. Surette MG. The cystic fibrosis lung microbiome. Ann Am Thorac Soc 2014; 11:S61–S65 [View Article] [PubMed]
     [Google Scholar]
  6. Thornton CS, Acosta N, Surette MG, Parkins MD. Exploring the cystic fibrosis lung microbiome: making the most of a sticky situation. J Pediatric Infect Dis Soc 2022; 11:S13–S22 [View Article] [PubMed]
     [Google Scholar]
  7. Acosta N, Whelan FJ, Somayaji R, Poonja A, Surette MG et al. The evolving cystic fibrosis microbiome: a comparative cohort study spanning 16 years. Ann Am Thorac Soc 2017; 14:1288–1297 [View Article] [PubMed]
     [Google Scholar]
  8. Cuthbertson L, Walker AW, Oliver AE, Rogers GB, Rivett DW et al. Lung function and microbiota diversity in cystic fibrosis. Microbiome 2020; 8:45 [View Article] [PubMed]
     [Google Scholar]
  9. Hampton TH, Green DM, Cutting GR, Morrison HG, Sogin ML et al. The microbiome in pediatric cystic fibrosis patients: the role of shared environment suggests a window of intervention. Microbiome 2014; 2:14 [View Article] [PubMed]
     [Google Scholar]
  10. Folkesson A, Jelsbak L, Yang L, Johansen HK, Ciofu O et al. Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective. Nat Rev Microbiol 2012; 10:841–851 [View Article] [PubMed]
     [Google Scholar]
  11. Hogardt M, Heesemann J. Microevolution of Pseudomonas aeruginosa to a chronic pathogen of the cystic fibrosis lung. Curr Top Microbiol Immunol 2013; 358:91–118 [View Article] [PubMed]
     [Google Scholar]
  12. Schick A, Kassen R. Rapid diversification of Pseudomonas aeruginosa in cystic fibrosis lung-like conditions. Proc Natl Acad Sci U S A 2018; 115:10714–10719 [View Article] [PubMed]
     [Google Scholar]
  13. Smith EE, Buckley DG, Wu Z, Saenphimmachak C, Hoffman LR et al. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci U S A 2006; 103:8487–8492 [View Article] [PubMed]
     [Google Scholar]
  14. Jorth P, Staudinger BJ, Wu X, Hisert KB, Hayden H et al. Regional isolation drives bacterial diversification within cystic fibrosis lungs. Cell Host Microbe 2015; 18:307–319 [View Article] [PubMed]
     [Google Scholar]
  15. Cullen L, McClean S. Bacterial adaptation during chronic respiratory infections. Pathogens 2015; 4:66–89 [View Article] [PubMed]
     [Google Scholar]
  16. Winstanley C, O’Brien S, Brockhurst MA. Pseudomonas aeruginosa evolutionary adaptation and diversification in cystic fibrosis chronic lung infections. Trends Microbiol 2016; 24:327–337 [View Article] [PubMed]
     [Google Scholar]
  17. Gröschel MI, Meehan CJ, Barilar I, Diricks M, Gonzaga A et al. The phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist Stenotrophomonas maltophilia. Nat Commun 2020; 11:2044 [View Article] [PubMed]
     [Google Scholar]
  18. Mercier-Darty M, Royer G, Lamy B, Charron C, Lemenand O et al. Comparative whole-genome phylogeny of animal, environmental, and human strains confirms the genogroup organization and diversity of the Stenotrophomonas maltophilia complex. Appl Environ Microbiol 2020; 86:e02919-19 [View Article] [PubMed]
     [Google Scholar]
  19. Pompilio A, Crocetta V, Ghosh D, Chakrabarti M, Gherardi G et al. Stenotrophomonas maltophilia phenotypic and genotypic diversity during a 10-year colonization in the lungs of a cystic fibrosis patient. Front Microbiol 2016; 7:1551 [View Article] [PubMed]
     [Google Scholar]
  20. Steinmann J, Mamat U, Abda EM, Kirchhoff L, Streit WR et al. Analysis of phylogenetic variation of Stenotrophomonas maltophilia reveals human-specific branches. Front Microbiol 2018; 9:806 [View Article] [PubMed]
     [Google Scholar]
  21. Turrientes MC, Baquero MR, Sánchez MB, Valdezate S, Escudero E et al. Polymorphic mutation frequencies of clinical and environmental Stenotrophomonas maltophilia populations. Appl Environ Microbiol 2010; 76:1746–1758 [View Article] [PubMed]
     [Google Scholar]
  22. McDaniel MS, Schoeb T, Swords WE. Cooperativity between Stenotrophomonas maltophilia and Pseudomonas aeruginosa during polymicrobial airway infections. Infect Immun 2020; 88:e00855-19 [View Article] [PubMed]
     [Google Scholar]
  23. McDaniel MS, Lindgren NR, Billiot CE, Valladares KN, Sumpter NA et al. Pseudomonas aeruginosa promotes persistence of Stenotrophomonas maltophilia via increased adherence to depolarized respiratory epithelium. Microbiol Spectr 2022e0384622 [View Article]
     [Google Scholar]
  24. Lindgren NR, McDaniel MS, Novak L, Swords WE. Acute polymicrobial airway infections: analysis in cystic fibrosis mice. Microbiology 2022; 169:001290 [View Article] [PubMed]
     [Google Scholar]
  25. Crossman LC, Gould VC, Dow JM, Vernikos GS, Okazaki A et al. The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants. Genome Biol 2008; 9:R74 [View Article] [PubMed]
     [Google Scholar]
  26. Merritt JH, Kadouri DE, O’Toole GA. Growing and analyzing static biofilms. Curr Protoc Microbiol 2005 [View Article] [PubMed]
     [Google Scholar]
  27. Goncz KK, Kunzelmann K, Xu Z, Gruenert DC. Targeted replacement of normal and mutant CFTR sequences in human airway epithelial cells using DNA fragments. Hum Mol Genet 1998; 7:1913–1919 [View Article] [PubMed]
     [Google Scholar]
  28. Abricate TS. Github. 10.1128/AAC.00483-19. n.d
  29. Liu B, Zheng D, Zhou S, Chen L, Yang J. VFDB 2022: a general classification scheme for bacterial virulence factors. Nucleic Acids Res 2022; 50:D912–D917 [View Article] [PubMed]
     [Google Scholar]
  30. Okazaki A, Avison MB. Induction of L1 and L2 beta-lactamase production in Stenotrophomonas maltophilia is dependent on an AmpR-type regulator. Antimicrob Agents Chemother 2008; 52:1525–1528 [View Article] [PubMed]
     [Google Scholar]
  31. Okazaki A, Avison MB. Aph(3’)-IIc, an aminoglycoside resistance determinant from Stenotrophomonas maltophilia. Antimicrob Agents Chemother 2007; 51:359–360 [View Article] [PubMed]
     [Google Scholar]
  32. Hu R-M, Huang K-J, Wu L-T, Hsiao Y-J, Yang T-C. Induction of L1 and L2 beta-lactamases of Stenotrophomonas maltophilia. Antimicrob Agents Chemother 2008; 52:1198–1200 [View Article] [PubMed]
     [Google Scholar]
  33. Pompilio A, Crocetta V, De Nicola S, Verginelli F, Fiscarelli E et al. Cooperative pathogenicity in cystic fibrosis: Stenotrophomonas maltophilia modulates Pseudomonas aeruginosa virulence in mixed biofilm. Front Microbiol 2015; 6:951 [View Article] [PubMed]
     [Google Scholar]
  34. Bertrand JJ, West JT, Engel JN. Genetic analysis of the regulation of type IV pilus function by the Chp chemosensory system of Pseudomonas aeruginosa. J Bacteriol 2010; 192:994–1010 [View Article] [PubMed]
     [Google Scholar]
  35. Whitchurch CB, Leech AJ, Young MD, Kennedy D, Sargent JL et al. Characterization of a complex chemosensory signal transduction system which controls twitching motility in Pseudomonas aeruginosa. Mol Microbiol 2004; 52:873–893 [View Article] [PubMed]
     [Google Scholar]
  36. Liao Y-C, Lin S-H, Lin H-H. Completing bacterial genome assemblies: strategy and performance comparisons. Sci Rep 2015; 5:8747 [View Article] [PubMed]
     [Google Scholar]
  37. Schmid M, Frei D, Patrignani A, Schlapbach R, Frey JE et al. Pushing the limits of de novo genome assembly for complex prokaryotic genomes harboring very long, near identical repeats. Nucleic Acids Res 2018; 46:8953–8965 [View Article] [PubMed]
     [Google Scholar]
  38. Browne PD, Nielsen TK, Kot W, Aggerholm A, Gilbert MTP et al. GC bias affects genomic and metagenomic reconstructions, underrepresenting GC-poor organisms. Gigascience 2020; 9:giaa008 [View Article] [PubMed]
     [Google Scholar]
  39. Chen Y-C, Liu T, Yu C-H, Chiang T-Y, Hwang C-C. Effects of GC bias in next-generation-sequencing data on de novo genome assembly. PLoS ONE 2013; 8:e62856 [View Article] [PubMed]
     [Google Scholar]
  40. Jun S-R, Wassenaar TM, Nookaew I, Hauser L, Wanchai V et al. Diversity of Pseudomonas genomes, including populus-associated isolates, as revealed by comparative genome analysis. Appl Environ Microbiol 2016; 82:375–383 [View Article] [PubMed]
     [Google Scholar]
  41. Klockgether J, Cramer N, Wiehlmann L, Davenport CF, Tümmler B. Pseudomonas aeruginosa genomic structure and diversity. Front Microbiol 2011; 2:150 [View Article] [PubMed]
     [Google Scholar]
  42. Holt KE, Wertheim H, Zadoks RN, Baker S, Whitehouse CA et al. Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proc Natl Acad Sci U S A 2015; 112:E3574–E3581 [View Article] [PubMed]
     [Google Scholar]
  43. Xiao Y, Jiang R, Wu X, Zhong Q, Li Y et al. Comparative genomic analysis of Stenotrophomonas maltophilia strain W18 reveals its adaptative genomic features for degrading polycyclic aromatic hydrocarbons. Microbiol Spectr 2021; 9:e0142021 [View Article] [PubMed]
     [Google Scholar]
  44. Xu Y, Cheng T, Rao Q, Zhang S, Ma YL. Comparative genomic analysis of Stenotrophomonas maltophilia unravels their genetic variations and versatility trait. J Appl Genet 2023; 64:351–360 [View Article] [PubMed]
     [Google Scholar]
  45. Patil PP, Kumar S, Midha S, Gautam V, Patil PB. Taxonogenomics reveal multiple novel genomospecies associated with clinical isolates of Stenotrophomonas maltophilia. Microb Genom 2018; 4:e000207 [View Article] [PubMed]
     [Google Scholar]
  46. Lira F, Berg G, Martínez JL. Double-face meets the bacterial world: the opportunistic pathogen Stenotrophomonas maltophilia. Front Microbiol 2017; 8:2190 [View Article] [PubMed]
     [Google Scholar]
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Comparative genomics of clinical Stenotrophomonas maltophilia isolates reveals genetic diversity which correlates with colonization and persistence in vivo
Microbiology 169, 001408 (2023); https://doi.org/10.1099/mic.0.001408
/content/journal/micro/10.1099/mic.0.001408
/content/journal/micro/10.1099/mic.0.001408
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