1887

Abstract

is an important nosocomial pathogen causing various opportunistic infections, such as urinary tract infections, bacteremia and sometimes even hospital outbreaks. The recent emergence and spread of multidrug-resistant (MDR) strains further pose serious threats to global public health. This bacterium is also ubiquitously found in natural environments, but the genomic differences between clinical and environmental isolates are not clear, including those between and its close relatives. In this study, we performed a large-scale genome analysis of and closely related species (referred to as the ‘ complex’), including more than 200 clinical and environmental strains newly sequenced here. Our analysis revealed their phylogenetic relationships and complex global population structure, comprising 14 clades, which were defined based on whole-genome average nucleotide identity. Clades 10, 11, 12 and 13 corresponded to , , and , respectively. Several clades exhibited distinct genome sizes and GC contents and a negative correlation of these genomic parameters was observed in each clade, which was associated with the acquisition of mobile genetic elements (MGEs), but different types of MGEs, plasmids or prophages (and other integrative elements), were found to contribute to the generation of these genomic variations. Importantly, clades 1 and 2 mostly comprised clinical or hospital environment isolates and accumulated a wide range of antimicrobial resistance genes, including various extended-spectrum β-lactamase and carbapenemase genes, and fluoroquinolone target site mutations, leading to a high proportion of MDR strains. This finding suggests that clades 1 and 2 represent hospital-adapted lineages in the complex although their potential virulence is currently unknown. These data provide an important genomic basis for reconsidering the classification of this group of bacteria and reveal novel insights into their evolution, biology and differential importance in clinical settings.

Funding
This study was supported by the:
  • Ministry of Education, Culture, Sports, Science and Technology
    • Principle Award Recipient: DeboraSatie Nagano
  • KAKENHI from Japan Society for the Promotion of Science (Award 18K16175)
    • Principle Award Recipient: TetsuyaHayashi
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000793
2022-03-22
2024-04-23
Loading full text...

Full text loading...

/deliver/fulltext/mgen/8/3/mgen000793.html?itemId=/content/journal/mgen/10.1099/mgen.0.000793&mimeType=html&fmt=ahah

References

  1. Mahlen SD. Serratia infections: from military experiments to current practice. Clin Microbiol Rev 2011; 24:755–791 [View Article] [PubMed]
    [Google Scholar]
  2. Fernández AL, Adrio B, Martínez Cereijo JM, Martínez Monzonis MA, El-Diasty MM et al. Clinical study of an outbreak of postoperative mediastinitis caused by Serratia marcescens in adult cardiac surgery. Interact Cardiovasc Thorac Surg 2020; 30:523–527 [View Article] [PubMed]
    [Google Scholar]
  3. Fleisch F, Zimmermann-Baer U, Zbinden R, Bischoff G, Arlettaz R et al. Three consecutive outbreaks of Serratia marcescens in a neonatal intensive care unit. Clin Infect Dis 2002; 34:767–773 [View Article] [PubMed]
    [Google Scholar]
  4. Hejazi A, Aucken HM, Falkiner FR. Epidemiology and susceptibility of serratia marcescens in a large general hospital over an 8-year period. J Hosp Infect 2000; 45:42–46 [View Article] [PubMed]
    [Google Scholar]
  5. Herbert S, Halvorsen DS, Leong T, Franklin C, Harrington G et al. Large outbreak of infection and colonization with gram-negative pathogens carrying the metallo- beta -lactamase gene blaIMP-4 at a 320-bed tertiary hospital in Australia. Infect Control Hosp Epidemiol 2007; 28:98–101 [View Article] [PubMed]
    [Google Scholar]
  6. Nastro M, Monge R, Zintgraff J, Vaulet LG, Boutureira M et al. First nosocomial outbreak of VIM-16-producing Serratia marcescens in Argentina. Clin Microbiol Infect 2013; 19:617–619 [View Article] [PubMed]
    [Google Scholar]
  7. Naumiuk L, Baraniak A, Gniadkowski M, Krawczyk B, Rybak B et al. Molecular epidemiology of Serratia marcescens in two hospitals in Gdańsk, Poland, over a 5-year period. J Clin Microbiol 2004; 42:3108–3116 [View Article] [PubMed]
    [Google Scholar]
  8. Vetter L, Schuepfer G, Kuster SP, Rossi M. A hospital-wide outbreak of Serratia marcescens, and Ishikawa’s “Fishbone” analysis to support outbreak control. Qual Manag Health Care 2016; 25:1–7 [View Article] [PubMed]
    [Google Scholar]
  9. Moradigaravand D, Boinett CJ, Martin V, Peacock SJ, Parkhill J. Recent independent emergence of multiple multidrug-resistant Serratia marcescens clones within the United Kingdom and Ireland. Genome Res 2016; 26:1101–1109 [View Article] [PubMed]
    [Google Scholar]
  10. Stock I, Grueger T, Wiedemann B. Natural antibiotic susceptibility of strains of Serratia marcescens and the S. liquefaciens complex: S. liquefaciens sensu stricto, S. proteamaculans and S. grimesii . Int J Antimicrob Agents 2003; 22:35–47 [View Article] [PubMed]
    [Google Scholar]
  11. Hopkins KL, Findlay J, Meunier D, Cummins M, Curtis S et al. Serratia marcescens producing SME carbapenemases: an emerging resistance problem in the UK?. J Antimicrob Chemother 2017; 72:1535–1537 [View Article]
    [Google Scholar]
  12. Ivanova D, Markovska R, Hadjieva N, Schneider I, Mitov I et al. Extended-spectrum β-lactamase-producing Serratia marcescens outbreak in a Bulgarian hospital. J Hosp Infect 2008; 70:60–65 [View Article]
    [Google Scholar]
  13. Abbott S. Klebsiella, Enterobacter, Citrobacter and Serratia. In Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH. eds Manual of Clinical Microbiology Washington, DC: ASM Press; 1999 pp 475–482
    [Google Scholar]
  14. Szewzyk U, Szewzyk R, Stenström TA. Growth and survival of Serratia marcescens under aerobic and anaerobic conditions in the presence of materials from blood bags. J Clin Microbiol 1993; 31:1826–1830 [View Article]
    [Google Scholar]
  15. Iguchi A, Nagaya Y, Pradel E, Ooka T, Ogura Y et al. Genome evolution and plasticity of Serratia marcescens, an important multidrug-resistant nosocomial pathogen. Genome Biol Evol 2014; 6:2096–2110 [View Article]
    [Google Scholar]
  16. Abreo E, Altier N. Pangenome of Serratia marcescens strains from nosocomial and environmental origins reveals different populations and the links between them. Sci Rep 2019; 9:46 [View Article] [PubMed]
    [Google Scholar]
  17. Matteoli FP, Pedrosa-Silva F, Dutra-Silva L, Giachini AJ. The global population structure and beta-lactamase repertoire of the opportunistic pathogen Serratia marcescens . Genomics 2021; 113:3523–3532 [View Article] [PubMed]
    [Google Scholar]
  18. Saralegui C, Ponce-Alonso M, Pérez-Viso B, Moles Alegre L, Escribano E et al. Genomics of Serratia marcescens isolates causing outbreaks in the same pediatric unit 47 years apart: position in an updated phylogeny of the species. Front Microbiol 2020; 11:451 [View Article] [PubMed]
    [Google Scholar]
  19. Adeolu M, Alnajar S, Naushad S, S Gupta R. Genome-based phylogeny and taxonomy of the “Enterobacteriales”: proposal for Enterobacterales ord. nov. divided into the families Enterobacteriaceae, Erwiniaceae fam. nov., Pectobacteriaceae fam. nov., Yersiniaceae fam. nov., Hafniaceae fam. nov., Morganellaceae fam. nov., and Budviciaceae fam. nov. Int J Syst Evol Microbiol 2016; 66:5575–5599 [View Article]
    [Google Scholar]
  20. Ajithkumar B, Ajithkumar VP, Iriye R, Doi Y, Sakai T. Spore-forming Serratia marcescens subsp. sakuensis subsp. nov., isolated from a domestic wastewater treatment tank. Int J Syst Evol Microbiol 2003; 53:253–258 [View Article] [PubMed]
    [Google Scholar]
  21. Cheng TH, Saidin J, Danish-Daniel M, Gan HM, Mat Isa MN et al. Genome sequence of Serratia marcescens subsp. sakuensis strain K27, a marine bacterium isolated from sponge (Haliclona amboinensis). Genome Announc 2018; 6:e00022–18 [View Article]
    [Google Scholar]
  22. Doijad S, Chakraborty T. Genome-based analyses indicate that Serratia marcescens subsp. marcescens and Serratia marcescens subsp. sakuensis do not merit separation to subspecies status. Int J Syst Evol Microbiol 2019; 69:3924–3926 [View Article]
    [Google Scholar]
  23. Parks DH, Chuvochina M, Chaumeil P-A, Rinke C, Mussig AJ et al. A complete domain-to-species taxonomy for Bacteria and Archaea. Nat Biotechnol 2020; 38:1079–1086 [View Article] [PubMed]
    [Google Scholar]
  24. Richter M, Rosselló-Móra R. Shifting the genomic gold standard for the prokaryotic species definition. Proc Natl Acad Sci U S A 2009; 106:19126–19131 [View Article] [PubMed]
    [Google Scholar]
  25. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article] [PubMed]
    [Google Scholar]
  26. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 2013; 30:772–780 [View Article] [PubMed]
    [Google Scholar]
  27. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 2014; 30:1312–1313 [View Article] [PubMed]
    [Google Scholar]
  28. Yu G, Smith DK, Zhu H, Guan Y, Lam T-Y. Ggtree: an r package for visualization and annotation of phylogenetic trees with their covariates and other associated data. Methods Ecol Evol 2017; 8:28–36 [View Article]
    [Google Scholar]
  29. Pritchard L, Glover RH, Humphris S, Elphinstone JG, Toth IK. Genomics and taxonomy in diagnostics for food security: soft-rotting enterobacterial plant pathogens. Anal Methods 2016; 8:12–24 [View Article]
    [Google Scholar]
  30. Sievers F, Higgins DG. Clustal Omega for making accurate alignments of many protein sequences. Protein Sci 2018; 27:135–145 [View Article] [PubMed]
    [Google Scholar]
  31. Rice P, Longden I, Bleasby A. EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet 2000; 16:276–277 [View Article] [PubMed]
    [Google Scholar]
  32. Farmer JJ, Silva F, Williams DR. Isolation of Serratia marcescens on deoxyribonuclease-toluidine blue-cephalothin agar. Appl Microbiol 1973; 25:151–152 [View Article] [PubMed]
    [Google Scholar]
  33. Kajitani R, Yoshimura D, Ogura Y, Gotoh Y, Hayashi T et al. Platanus_B: an accurate de novo assembler for bacterial genomes using an iterative error-removal process. DNA Res 2020; 27:27 [View Article] [PubMed]
    [Google Scholar]
  34. Parks DH, Imelfort M, Skennerton CT, Hugenholtz P, Tyson GW. CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res 2015; 25:1043–1055 [View Article] [PubMed]
    [Google Scholar]
  35. Tanizawa Y, Fujisawa T, Nakamura Y. DFAST: a flexible prokaryotic genome annotation pipeline for faster genome publication. Bioinformatics 2018; 34:1037–1039 [View Article] [PubMed]
    [Google Scholar]
  36. Murtagh F, Legendre P. Ward’s hierarchical agglomerative clustering method: which algorithms implement ward’s criterion?. J Classif 2014; 31:274–295 [View Article]
    [Google Scholar]
  37. Harris AKP, Williamson NR, Slater H, Cox A, Abbasi S et al. The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation. Microbiology (Reading) 2004; 150:3547–3560 [View Article] [PubMed]
    [Google Scholar]
  38. Buchfink B, Xie C, Huson DH. Fast and sensitive protein alignment using DIAMOND. Nat Methods 2015; 12:59–60 [View Article] [PubMed]
    [Google Scholar]
  39. Yabe S, Fukushima J. Complete genome sequence of temperature-dependent pigment-producing Serratia marcescens ATCC 274. Microbiol Resour Announc 2020; 9:e00164-20 [View Article] [PubMed]
    [Google Scholar]
  40. Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 2014; 58:3895–3903 [View Article] [PubMed]
    [Google Scholar]
  41. Brynildsrud O, Bohlin J, Scheffer L, Eldholm V. Rapid scoring of genes in microbial pan-genome-wide association studies with Scoary. Genome Biol 2016; 17:238 [View Article] [PubMed]
    [Google Scholar]
  42. R Core Team R: A language and environment for statistical computing. Vienna, Austria: 2020 https://www.R-project.org/
  43. Fisher RA. The logic of inductive inference. J R Stat Soc 1935; 98:39 [View Article]
    [Google Scholar]
  44. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society: Series B (Methodological) 1995; 57:289–300 [View Article]
    [Google Scholar]
  45. Inouye M, Dashnow H, Raven L-A, Schultz MB, Pope BJ et al. SRST2: Rapid genomic surveillance for public health and hospital microbiology labs. Genome Med 2014; 6:90 [View Article] [PubMed]
    [Google Scholar]
  46. Huang W, Li L, Myers JR, Marth GT. ART: a next-generation sequencing read simulator. Bioinformatics 2012; 28:593–594 [View Article] [PubMed]
    [Google Scholar]
  47. Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J et al. BLAST+: architecture and applications. BMC Bioinformatics 2009; 10:421 [View Article] [PubMed]
    [Google Scholar]
  48. Hopkins KL, Davies RH, Threlfall EJ. Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developments. Int J Antimicrob Agents 2005; 25:358–373 [View Article] [PubMed]
    [Google Scholar]
  49. Nawaz M, Sung K, Kweon O, Khan S, Nawaz S et al. Characterisation of novel mutations involved in quinolone resistance in Escherichia coli isolated from imported shrimp. Int J Antimicrob Agents 2015; 45:471–476 [View Article] [PubMed]
    [Google Scholar]
  50. Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18:268–281 [View Article] [PubMed]
    [Google Scholar]
  51. Livermore DM, Winstanley TG, Shannon KP. Interpretative reading: recognizing the unusual and inferring resistance mechanisms from resistance phenotypes. J Antimicrob Chemother 2001; 48 Suppl 1:87–102 [View Article] [PubMed]
    [Google Scholar]
  52. Strobel G, Li J-Y, Sugawara F, Koshino H, Harper J et al. Oocydin A, A chlorinated macrocyclic lactone with potent anti-oomycete activity from Serratia marcescens . Microbiology (Reading) 1999; 145 (Pt 12):3557–3564 [View Article] [PubMed]
    [Google Scholar]
  53. Matilla MA, Udaondo Z, Krell T, Salmond GPC. Genome Sequence of Serratia marcescens MSU97, a plant-associated bacterium that makes multiple antibiotics. Genome Announc 2017; 5:e01752-16 [View Article] [PubMed]
    [Google Scholar]
  54. Sakuraoka R, Suzuki T, Morohoshi T. Distribution and genetic diversity of genes involved in quorum sensing and prodigiosin biosynthesis in the complete genome sequences of Serratia marcescens . Genome Biol Evol 2019; 11:931–936 [View Article] [PubMed]
    [Google Scholar]
  55. Fineran PC, Iglesias Cans MC, Ramsay JP, Wilf NM, Cossyleon D et al. Draft genome sequence of Serratia sp. strain ATCC 39006, a model bacterium for analysis of the biosynthesis and regulation of prodigiosin, a carbapenem, and gas vesicles. Genome Announc 2013; 1:e01039-13 [View Article] [PubMed]
    [Google Scholar]
  56. Daubin V, Lerat E, Perrière G. The source of laterally transferred genes in bacterial genomes. Genome Biol 2003; 4:R57 [View Article]
    [Google Scholar]
  57. Rocha EPC, Danchin A. Base composition bias might result from competition for metabolic resources. Trends Genet 2002; 18:291–294 [View Article]
    [Google Scholar]
  58. Thompson SA, Maani EV, Lindell AH, King CJ, McArthur JV. Novel tetracycline resistance determinant isolated from an environmental strain of Serratia marcescens . Appl Environ Microbiol 2007; 73:2199–2206 [View Article]
    [Google Scholar]
  59. Correia S, Poeta P, Hébraud M, Capelo JL, Igrejas G. Mechanisms of quinolone action and resistance: where do we stand?. J Med Microbiol 2017; 66:551–559 [View Article]
    [Google Scholar]
  60. Goluszko P, Nowacki MR. Extracellular haemolytic activity of Serratia marcescens . FEMS Microbiol Lett 1989; 52:207–211 [View Article]
    [Google Scholar]
  61. Cho G-S, Stein M, Brinks E, Rathje J, Lee W et al. Serratia nevei sp. nov. and Serratia bockelmannii sp. nov., isolated from fresh produce in Germany and reclassification of Serratia marcescens subsp. sakuensis Ajithkumar et al. 2003 as a later heterotypic synonym of Serratia marcescens subsp. marcescens . Syst Appl Microbiol 2020; 43:126055 [View Article] [PubMed]
    [Google Scholar]
  62. Kumar N, Browne HP, Viciani E, Forster SC, Clare S et al. Adaptation of host transmission cycle during Clostridium difficile speciation. Nat Genet 2019; 51:1315–1320 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000793
Loading
/content/journal/mgen/10.1099/mgen.0.000793
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

EXCEL
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error