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Volume 6, Issue 11

Development of acute and lung mono-challenge models in mice using oropharyngeal aspiration Open Access

Abstract

Antimicrobial-resistant pathogens such as and can cause potentially fatal infections in susceptible individuals, with respiratory tract infections among the most common clinical presentations. The development of novel treatments or prophylactic interventions to combat these infections is urgently needed and requires robust, reliable animal models for their preclinical evaluation. In particular, the bacterial burden needs to be accurately determined before and after administration of the potential therapy under evaluation to quantify the effectiveness of the treatment. We provide two reliable, non-invasive murine acute lung challenge models with either or using an oropharyngeal aspiration technique, which has been widely overlooked in studies testing vaccines or treatments for these pathogens. Here, we show that this non-surgical technique to deliver suspensions into mouse lungs does not significantly impact animal welfare (based on welfare monitoring and weight) and allows uniform bilateral distribution of the bacterial dose, resulting in even bioburden in both lungs. The optimal timepoint for humane killing and organ harvest was 24 h after challenge for both pathogens, and at least 4×10 and 10 c.f.u. per mouse were needed to obtain a reproducible or bioburden, respectively. These mouse challenge models offer a valuable tool to assess therapeutic interventions against or infections.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Acinetobacter baumannii , mouse lung challenge model , oropharyngeal aspiration and Pseudomonas aeruginosa
Funding
This study was supported by the:
  • HORIZON EUROPE Marie Sklodowska-Curie Actions (Award 860325)
    • Principle Award Recipient: SiobhánMcClean
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-11-21
2024-12-02
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References

  1. Diggle SP, Whiteley M. Microbe Profile: Pseudomonas aeruginosa: opportunistic pathogen and lab rat. Microbiology 2020; 166:30–33 [View Article] [PubMed]
     [Google Scholar]
  2. Ayoub Moubareck C, Hammoudi Halat D. Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in A Threatening Nosocomial Pathogen. Antibiotics 2020; 9:119 [View Article] [PubMed]
     [Google Scholar]
  3. Collaborators G. Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the global burden of disease study 2019. Lancet 2022; 400:2221–2248
     [Google Scholar]
  4. European Centre for Disease Prevention and Control Annual epidemiological report for 2019 – Healthcare associated infections acquired in intensive care units. In In: ECDC. Annual Epidemiological Report for 2019 Stockholm: ECDC; 2023 https://www.ecdc.europa.eu/en/publications-data/healthcare-associated-infections-intensive-care-units-2019
     [Google Scholar]
  5. Garnacho-Montero J, Ortiz-Leyba C, Fernández-Hinojosa E, Aldabó-Pallás T, Cayuela A et al. Acinetobacter baumannii ventilator-associated pneumonia: epidemiological and clinical findings. Intensive Care Med 2005; 31:649–655 [View Article] [PubMed]
     [Google Scholar]
  6. Costa MI, Cipriano A, Santos FV, Valdoleiros SR, Furtado I et al. Clinical profile and microbiological aetiology diagnosis in adult patients hospitalized with community-acquired pneumonia. Pulmonology 2022; 28:358–367 [View Article] [PubMed]
     [Google Scholar]
  7. Ma C, McClean S. Mapping Global Prevalence of Acinetobacter baumannii and Recent Vaccine Development to Tackle It. Vaccines 2021; 9:570 [View Article] [PubMed]
     [Google Scholar]
  8. Emerson J, Rosenfeld M, McNamara S, Ramsey B, Gibson RL. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol 2002; 34:91–100 [View Article] [PubMed]
     [Google Scholar]
  9. Courtney JM, Bradley J, Mccaughan J, O’Connor TM, Shortt C et al. Predictors of mortality in adults with cystic fibrosis. Pediatr Pulmonol 2007; 42:525–532 [View Article] [PubMed]
     [Google Scholar]
  10. Durda-Masny M, Goździk-Spychalska J, John A, Czaiński W, Stróżewska W et al. The determinants of survival among adults with cystic fibrosis-a cohort study. J Physiol Anthropol 2021; 40:19 [View Article] [PubMed]
     [Google Scholar]
  11. Rosenfeld M. Association of Pseudomonas aeruginosa infection stage with lung function trajectory in children with cystic fibrosis. J Cyst Fibros 156900134–00140
     [Google Scholar]
  12. Malhotra S, Hayes D, Wozniak DJ. Cystic fibrosis and Pseudomonas aeruginosa: the host-microbe interface. Clin Microbiol Rev 2019; 32:e00138–00118 [View Article] [PubMed]
     [Google Scholar]
  13. Miller WR, Arias CA. ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics. Nat Rev Microbiol 2024; 22:598–616 [View Article] [PubMed]
     [Google Scholar]
  14. Azam MW, Khan AU. Updates on the pathogenicity status of Pseudomonas aeruginosa. Drug Discov Today 2019; 24:350–359 [View Article] [PubMed]
     [Google Scholar]
  15. CDC Antibiotic Resistance Threats in the United States 2019 [View Article]
     [Google Scholar]
  16. WHO Bacterial Priority Pathogens List, 2024: Bacterial Pathogens of Public Health Importance to Guide Research, Development and Strategies to Prevent and Control Antimicrobial Resistance Geneva: World Health Organization; 2024
     [Google Scholar]
  17. Chen W. Current advances and challenges in the development of Acinetobacter vaccines. Hum Vaccin Immunother 2015; 11:2495–2500 [View Article] [PubMed]
     [Google Scholar]
  18. Wood SJ, Kuzel TM, Shafikhani SH. Pseudomonas aeruginosa: infections, animal modeling, and therapeutics. Cells 2023; 12:199 [View Article] [PubMed]
     [Google Scholar]
  19. Reyne N, McCarron A, Cmielewski P, Parsons D, Donnelley M. To bead or not to bead: a review of Pseudomonas aeruginosa lung infection models for cystic fibrosis. Front Physiol 2023; 14:1104856 [View Article] [PubMed]
     [Google Scholar]
  20. Mizgerd JP, Skerrett SJ. Animal models of human pneumonia. Am J Physiol Lung Cell Mol Physiol 2008; 294:L387–98 [View Article] [PubMed]
     [Google Scholar]
  21. Bakker-Woudenberg IAJM. Experimental models of pulmonary infection. J Microbiol Methods 2003; 54:295–313 [View Article] [PubMed]
     [Google Scholar]
  22. Coleman FT, Mueschenborn S, Meluleni G, Ray C, Carey VJ et al. Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection. Proc Natl Acad Sci U S A 2003; 100:1949–1954 [View Article] [PubMed]
     [Google Scholar]
  23. Madenspacher JH, Fessler MB. A non-invasive and technically non-intensive method for induction and phenotyping of experimental bacterial Pneumonia in Mice. J Vis Exp 2016; 54508:54508 [View Article] [PubMed]
     [Google Scholar]
  24. Lakatos HF, Burgess HA, Thatcher TH, Redonnet MR, Hernady E et al. Oropharyngeal aspiration of a silica suspension produces a superior model of silicosis in the mouse when compared to intratracheal instillation. Exp Lung Res 2006; 32:181–199 [View Article] [PubMed]
     [Google Scholar]
  25. Galligioni V, Movia D, Ruiz-Pérez D, Sánchez-Morgado JM, Prina-Mello A. The case for modernizing biomedical research in ireland through the creation of an Irish 3Rs centre. Animals 2022; 12:1078 [View Article]
     [Google Scholar]
  26. De Soyza A, Hall AJ, Mahenthiralingam E, Drevinek P, Kaca W et al. Developing an international Pseudomonas aeruginosa reference panel. Microbiologyopen 2013; 2:1010–1023 [View Article] [PubMed]
     [Google Scholar]
  27. Lucchetti-Miganeh C, Redelberger D, Chambonnier G, Rechenmann F, Elsen S et al. Pseudomonas aeruginosa genome evolution in patients and under the hospital environment. Pathogens 2014; 3:309–340 [View Article] [PubMed]
     [Google Scholar]
  28. Cullen L, Weiser R, Olszak T, Maldonado RF, Moreira AS et al. Phenotypic characterization of an international Pseudomonas aeruginosa reference panel: strains of cystic fibrosis (CF) origin show less in vivo virulence than non-CF strains. Microbiology 2015; 161:1961–1977 [View Article] [PubMed]
     [Google Scholar]
  29. Schaub IG, Hauber FD. A biochemical and serological study of a group of identical unidentifiable gram-negative bacilli from human sources. J Bacteriol 1948; 56:379–385 [View Article] [PubMed]
     [Google Scholar]
  30. Tansho-Nagakawa S, Sato Y, Ubagai T, Kikuchi-Ueda T, Kamoshida GO et al. Histopathological analysis of Acinetobacter baumannii lung infection in a mouse model. Pol J Microbiol 2021; 70:469–477 [View Article] [PubMed]
     [Google Scholar]
  31. Lorenz A, Pawar V, Häussler S, Weiss S. Insights into host-pathogen interactions from state-of-the-art animal models of respiratory Pseudomonas aeruginosa infections. FEBS Lett 2016; 590:3941–3959 [View Article] [PubMed]
     [Google Scholar]
  32. Akkermans A, Chapsal J-M, Coccia EM, Depraetere H, Dierick J-F et al. Animal testing for vaccines. Implementing replacement, reduction and refinement: challenges and priorities. Biologicals 2020; 68:92–107 [View Article] [PubMed]
     [Google Scholar]
  33. Zeng Y, Jin H, Wang J, Guo C, Chen W et al. An optimized method for intratracheal instillation in mice. J Pharmacol Toxicol Methods 2022; 118:107230 [View Article] [PubMed]
     [Google Scholar]
  34. Freschi L, Bertelli C, Jeukens J, Moore MP, Kukavica-Ibrulj I et al. Genomic characterisation of an international Pseudomonas aeruginosa reference panel indicates that the two major groups draw upon distinct mobile gene pools. FEMS Microbiol Lett 2018; 365: [View Article] [PubMed]
     [Google Scholar]
  35. Lorè NI, Cigana C, De Fino I, Riva C, Juhas M et al. Cystic fibrosis-niche adaptation of Pseudomonas aeruginosa reduces virulence in multiple infection hosts. PLoS One 2012; 7:e35648 [View Article] [PubMed]
     [Google Scholar]
  36. Bragonzi A, Paroni M, Nonis A, Cramer N, Montanari S et al. Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence. Am J Respir Crit Care Med 2009; 180:138–145 [View Article] [PubMed]
     [Google Scholar]
  37. Jacobs AC, Thompson MG, Black CC, Kessler JL, Clark LP et al. AB5075, a highly virulent isolate of Acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments. mBio 2014; 5:10–1128 [View Article]
     [Google Scholar]
  38. Harris G, Kuo Lee R, Lam CK, Kanzaki G, Patel GB et al. A mouse model of Acinetobacter baumannii-associated pneumonia using a clinically isolated hypervirulent strain. Antimicrob Agents Chemother 2013; 57:3601–3613 [View Article] [PubMed]
     [Google Scholar]
  39. Bragonzi A. Murine models of acute and chronic lung infection with cystic fibrosis pathogens. Int J Med Microbiol 2010; 300:584–593 [View Article] [PubMed]
     [Google Scholar]
  40. van Faassen H, KuoLee R, Harris G, Zhao X, Conlan JW et al. Neutrophils play an important role in host resistance to respiratory infection with Acinetobacter baumannii in mice. Infect Immun 2007; 75:5597–5608 [View Article] [PubMed]
     [Google Scholar]
  41. Knapp S, Wieland CW, Florquin S, Pantophlet R, Dijkshoorn L et al. Differential roles of CD14 and toll-like receptors 4 and 2 in murine Acinetobacter pneumonia. Am J Respir Crit Care Med 2006; 173:122–129 [View Article] [PubMed]
     [Google Scholar]
  42. Bergamini G, Perico ME, Di Palma S, Sabatini D, Andreetta F et al. Mouse pneumonia model by Acinetobacter baumannii multidrug resistant strains: comparison between intranasal inoculation, intratracheal instillation and oropharyngeal aspiration techniques. PLoS One 2021; 16:e0260627 [View Article]
     [Google Scholar]
  43. Baker SM, Pociask D, Clements JD, McLachlan JB, Morici LA. Intradermal vaccination with a Pseudomonas aeruginosa vaccine adjuvanted with a mutant bacterial ADP-ribosylating enterotoxin protects against acute pneumonia. Vaccine 2019; 37:808–816 [View Article] [PubMed]
     [Google Scholar]
  44. Moustafa DA, Wu AW, Zamora D, Daly SM, Sturge CR et al. Peptide-conjugated phosphorodiamidate morpholino oligomers retain activity against multidrug-resistant Pseudomonas aeruginosa In Vitro and In Vivo. mBio 2021; 12:e02411-20 [View Article] [PubMed]
     [Google Scholar]
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Development of acute Pseudomonas aeruginosa and Acinetobacter baumannii lung mono-challenge models in mice using oropharyngeal aspiration
Access Microbiology 6, 000860.v3 (2024); https://doi.org/10.1099/acmi.0.000860.v3
/content/journal/acmi/10.1099/acmi.0.000860.v3
/content/journal/acmi/10.1099/acmi.0.000860.v3
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