Abstract:
:Treatment of Mycobacterium abscessus infections is extremely challenging due to its intrinsic resistance to most antibiotics, and research of pathogenesis is limited due to a lack of a practical in vivo model of infection. The objective of this study was to establish a simple in vivo model for M. abscessus infection, virulence, and drug testing in Galleria mellonella larvae. We inoculated larvae with M. abscessus bacteria and assessed histopathology, CFU count, and mortality with and without antibiotic treatment. We also constructed a luminescent, recombinant M. abscessus mutant, mDB158, and imaged infected larvae using the IVIS in vivo imaging system. M. abscessus proliferated and induced granuloma-like responses in infected larvae, leading to larval mortality. The G. mellonella model was further validated successfully by demonstration of the expected favorable antimicrobial effect of treatment with meropenem and the superiority of combination treatment (meropenem and tigecycline) over that with single agents. We then used IVIS imaging of larvae infected with luminescent M. abscessus, allowing live real-time assessment of bacterial load. We used this method to compare the antimicrobial effects of various antibiotics (meropenem, amikacin, linezolid, levofloxacin, etc.) on bacterial proliferation and larval survival. Meropenem and amikacin had the most favorable effects, correlating well with common clinical practice guidelines. These findings suggest G. mellonella to be an excellent in vivo model for research of M. abscessus infection, pathogenesis, and treatment. Luminescent M. abscessus and IVIS imaging further facilitates this model. Results obtained in this model clearly substantiated common clinical practice, thus validating the model as a predictor of treatment efficacy and outcome.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Meir M,Grosfeld T,Barkan Ddoi
10.1128/AAC.02539-17subject
Has Abstractpub_date
2018-03-27 00:00:00issue
4eissn
0066-4804issn
1098-6596pii
AAC.02539-17journal_volume
62pub_type
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2016-12-27 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.3.535
更新日期:1986-03-01 00:00:00
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更新日期:2016-08-22 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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abstract::Bacterial adaptation to external stresses and toxic compounds is a key step in the emergence of multidrug-resistant strains that are a serious threat to human health. Although some of the proteins and regulators involved in antibiotic resistance mechanisms have been described, no information is available to date conce...
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