Skip to content
1887

Abstract

Reports of β-lactamase-producing are increasing worldwide.

. This study aimed to elucidate the molecular characteristics and evolution of β-lactamase-producing .

A total of 159 clinical isolates were characterized using multi-locus sequence typing. Antimicrobial resistance genes and integrative and conjugative element (ICE) types were identified through PCR and DNA sequencing. The genetic structure of ICE was further investigated using whole-genome sequencing.

Out of 159 clinical isolates, 20.8% (=33) were β-lactamase producers. Thirteen sequence types (STs) were identified. ST 103, 155, 165 and 388 have been identified in previous studies, suggesting that strains with these STs tend to acquire the β-lactamase gene . Among β-lactamase producers, 66.7% (=22) of were located on ICE. The ICEs could be classified into two groups based on their sequence (types I and II). Among these strains, 2017-Y3 harboured a macrolide resistance gene, , in ICE. A comparative analysis of the ICE region of this strain and those from other countries suggested that each isolate was derived from ICE type I or II. These regions, including ), were similar to those of Tn, which is commonly found in .

This study revealed several STs associated with the acquisition of β-lactamase genes on ICEs. Additionally, ICE evolution involved the acquisition of exogenous genes. The accumulation of resistance genes in ICE raises concerns regarding the emergence of multidrug-resistant .

Funding
This study was supported by the:
  • Japan Society for the Promotion of Science (Award 20H01077)
    • Principle Award Recipient: ShojiSeyama
  • Research Institute of Meijo University
    • Principle Award Recipient: TakeakiWajima
  • Takeda Science Foundation
    • Principle Award Recipient: TakeakiWajima
  • Japan Society for the Promotion of Science (Award 23KJ1955)
    • Principle Award Recipient: EmiTanaka
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001904
2024-10-03
2025-01-14
Loading full text...

Full text loading...

References

  1. Murphy TF, Apicella MA. Nontypable Haemophilus influenzae: a review of clinical aspects, surface antigens, and the human immune response to infection. Rev Infect Dis 1987; 9:1–15 [View Article] [PubMed]
    [Google Scholar]
  2. Bender JM, Cox CM, Mottice S, She RC, Korgenski K et al. Invasive Haemophilus influenzae disease in Utah children: an 11-year population-based study in the era of conjugate vaccine. Clin Infect Dis 2010; 50:e41-46 [View Article] [PubMed]
    [Google Scholar]
  3. Suga S, Ishiwada N, Sasaki Y, Akeda H, Nishi J et al. A nationwide population-based surveillance of invasive Haemophilus influenzae diseases in children after the introduction of the Haemophilus influenzae type b vaccine in Japan. Vaccine 2018; 36:5678–5684 [View Article] [PubMed]
    [Google Scholar]
  4. Mikasa K, Aoki N, Aoki Y, Abe S, Iwata S et al. JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases: The Japanese Association for Infectious Diseases/Japanese Society of Chemotherapy - The JAID/JSC Guide to Clinical Management of Infectious Disease/Guideline-preparing Committee Respiratory Infectious Disease WG. J Infect Chemother 2016; 22:S1–S65 [View Article] [PubMed]
    [Google Scholar]
  5. Ishiwada N, Fujimaki K, Matsumoto T, Kiyota H, Tateda K et al. Nationwide surveillance of bacterial pathogens isolated from children conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2017: general overview of pathogenic antimicrobial susceptibility. J Infect Chemother 2021; 27:139–150 [View Article] [PubMed]
    [Google Scholar]
  6. Tanaka E, Hara N, Wajima T, Ochiai S, Seyama S et al. Emergence of Haemophilus influenzae with low susceptibility to quinolones and persistence in tosufloxacin treatment. J Glob Antimicrob Resist 2019; 18:104–108 [View Article] [PubMed]
    [Google Scholar]
  7. Gutmann L, Williamson R, Collatz E, Acar JF. Mechanisms of beta-lactam resistance in Haemophilus influenzae. Eur J Clin Microbiol Infect Dis 1988; 7:610–615 [View Article] [PubMed]
    [Google Scholar]
  8. Sahm DF, Jones ME, Hickey ML, Diakun DR, Mani SV et al. Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in Asia and Europe, 1997-1998. J Antimicrob Chemother 2000; 45:457–466 [View Article] [PubMed]
    [Google Scholar]
  9. Ubukata K, Shibasaki Y, Yamamoto K, Chiba N, Hasegawa K et al. Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. Antimicrob Agents Chemother 2001; 45:1693–1699 [View Article] [PubMed]
    [Google Scholar]
  10. Yamada S, Seyama S, Wajima T, Yuzawa Y, Saito M et al. β-Lactamase-non-producing ampicillin-resistant Haemophilus influenzae is acquiring multidrug resistance. J Infect Public Health 2020; 13:497–501 [View Article] [PubMed]
    [Google Scholar]
  11. Hasegawa K, Yamamoto K, Chiba N, Kobayashi R, Nagai K et al. Diversity of ampicillin-resistance genes in Haemophilus influenzae in Japan and the United States. Microb Drug Resist 2003; 9:39–46 [View Article] [PubMed]
    [Google Scholar]
  12. Tokimatsu I, Matsumoto T, Tsukada H, Fujikura Y, Miki M et al. Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2019-2020: General view of the pathogens’ antibacterial susceptibility. J Infect Chemother 2023; 29:731–743 [View Article] [PubMed]
    [Google Scholar]
  13. Potts CC, Rodriguez-Rivera LD, Retchless AC, Buono SA, Chen AT et al. Antimicrobial susceptibility survey of invasive Haemophilus influenzae in the United States in 2016. Microbiol Spectr 2022; 10:e0257921 [View Article] [PubMed]
    [Google Scholar]
  14. Hara N, Wajima T, Seyama S, Tanaka E, Shirai A et al. Isolation of multidrug-resistant Haemophilus influenzae harbouring multiple exogenous genes from a patient diagnosed with acute sinusitis. J Infect Chemother 2019; 25:385–387 [View Article] [PubMed]
    [Google Scholar]
  15. Johannessen H, Anthonisen IL, Zecic N, Hegstad K, Ranheim TE et al. Characterization and fitness cost of Tn7100, a novel integrative and conjugative element conferring multidrug resistance in Haemophilus influenzae. Front Microbiol 2022; 13:945411 [View Article] [PubMed]
    [Google Scholar]
  16. Michel C, Argudín MDLA, Wautier M, Echahidi F, Prevost B et al. Multiple interspecies recombination events documented by whole-genome sequencing in multidrug-resistant Haemophilus influenzae clinical isolates. Access Microbiol 2024; 6:000649.v3 [View Article] [PubMed]
    [Google Scholar]
  17. Seyama S, Wajima T, Suzuki M, Ushio M, Fujii T et al. Emergence and molecular characterization of Haemophilus influenzae harbouring mef(A). J Antimicrob Chemother 2017; 72:948–949 [View Article] [PubMed]
    [Google Scholar]
  18. Wajima T, Seyama S, Nakamura Y, Kashima C, Nakaminami H et al. Prevalence of macrolide-non-susceptible isolates among β-lactamase-negative ampicillin-resistant Haemophilus influenzae in a tertiary care hospital in Japan. J Glob Antimicrob Resist 2016; 6:22–26 [View Article] [PubMed]
    [Google Scholar]
  19. Meats E, Feil EJ, Stringer S, Cody AJ, Goldstein R et al. Characterization of encapsulated and noncapsulated Haemophilus influenzae and determination of phylogenetic relationships by multilocus sequence typing. J Clin Microbiol 2003; 41:1623–1636 [View Article] [PubMed]
    [Google Scholar]
  20. Juhas M, Power PM, Harding RM, Ferguson DJP, Dimopoulou ID et al. Sequence and functional analyses of Haemophilus spp. genomic islands. Genome Biol 2007; 8:R237 [View Article] [PubMed]
    [Google Scholar]
  21. Giufrè M, Cardines R, Marra M, Carollo M, Cerquetti M et al. Antibiotic susceptibility and molecular typing of invasive Haemophilus influenzae isolates, with emergence of ciprofloxacin resistance, 2017-2021, Italy. Microorganisms 2023; 11:315 [View Article] [PubMed]
    [Google Scholar]
  22. Heliodoro CIM, Bettencourt CR, Bajanca-Lavado MP. Molecular epidemiology of invasive haemophilus influenzae disease in portugal: an update of the post-vaccine period, 2011-2018. Eur J Clin Microbiol Infect Dis 2020; 39:1471–1480
    [Google Scholar]
  23. Tønnessen R, García I, Debech N, Lindstrøm JC, Wester AL et al. Molecular epidemiology and antibiotic resistance profiles of invasive Haemophilus influenzae from Norway 2017-2021. Front Microbiol 2022; 13:973257 [View Article] [PubMed]
    [Google Scholar]
  24. Tsang RSW, Shuel M, Whyte K, Hoang L, Tyrrell G et al. Antibiotic susceptibility and molecular analysis of invasive Haemophilus influenzae in Canada, 2007 to 2014. J Antimicrob Chemother 2017; 72:1314–1319 [View Article]
    [Google Scholar]
  25. Ubukata K, Morozumi M, Sakuma M, Adachi Y, Mokuno E et al. Genetic characteristics and antibiotic resistance of Haemophilus influenzae isolates from pediatric patients with acute otitis media after introduction of 13-valent pneumococcal conjugate vaccine in Japan. J Infect Chemother 2019; 25:720–726 [View Article] [PubMed]
    [Google Scholar]
  26. Fleury C, Resman F, Rau J, Riesbeck K. Prevalence, distribution and transfer of small β-lactamase-containing plasmids in Swedish Haemophilus influenzae. J Antimicrob Chemother 2014; 69:1238–1242 [View Article] [PubMed]
    [Google Scholar]
  27. Søndergaard A, San Millan A, Santos-Lopez A, Nielsen SM, Gonzalez-Zorn B et al. Molecular organization of small plasmids bearing blaTEM-1 and conferring resistance to β-lactams in Haemophilus influenzae. Antimicrob Agents Chemother 2012; 56:4958–4960 [View Article] [PubMed]
    [Google Scholar]
  28. Juhas M, Dimopoulou I, Robinson E, Elamin A, Harding R et al. Identification of another module involved in the horizontal transfer of the Haemophilus genomic island ICEHin1056. Plasmid 2013; 70:277–283 [View Article] [PubMed]
    [Google Scholar]
  29. Hegstad K, Mylvaganam H, Janice J, Josefsen E, Sivertsen A et al. Role of horizontal gene transfer in the development of multidrug resistance in Haemophilus influenzae. mSphere 2020; 5:e00969-19 [View Article] [PubMed]
    [Google Scholar]
  30. Tristram S, Jacobs MR, Appelbaum PC. Antimicrobial resistance in Haemophilus influenzae. Clin Microbiol Rev 2007; 20:368–389 [View Article] [PubMed]
    [Google Scholar]
  31. Uda K, Okubo Y, Kinoshita N, Morisaki N, Kasai M et al. Nationwide survey of indications for oral antimicrobial prescription for pediatric patients from 2013 to 2016 in Japan. J Infect Chemother 2019; 25:758–763 [View Article] [PubMed]
    [Google Scholar]
  32. The Government of Japan National Action Plan on Antimicrobial Resistance (AMR) 2023-2027; 2023
  33. Kusama Y, Tsuzuki S, Muraki Y, Koizumi R, Ishikane M et al. The effects of Japan’s National Action plan on antimicrobial resistance on antimicrobial use. Int J Infect Dis 2021; 103:154–156 [View Article] [PubMed]
    [Google Scholar]
  34. Nikolaou E, Hubbard ATM, Botelho J, Marschall TAM, Ferreira DM et al. Antibiotic resistance is associated with integrative and conjugative elements and genomic islands in naturally circulating Streptococcus pneumoniae isolates from adults in Liverpool, UK. Genes (Basel) 2020; 11:e625 [View Article] [PubMed]
    [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.001904
Loading
/content/journal/jmm/10.1099/jmm.0.001904
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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