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Published on: January 5, 2024
The Association between Transformation Ability and Antimicrobial Resistant Potential in Haemophilus influenzae
Emi Tanaka1, Takeaki Wajima1, Ruri Ota1
1Department of Microbiology, Faculty of Pharmacy, Meijo University.
Abstract:
The prevalence of quinolone low-susceptible Haemophilus influenzae has increased in Japan. Low quinolone susceptibility is caused by point mutations in target genes; however, it can also be caused by horizontal gene transfer via natural transformation. In this study, we examined whether this horizontal gene transfer could be associated with resistance to not only quinolones but also other antimicrobial agents. Horizontal transfer ability was quantified using the experimental transfer assay method for low quinolone susceptibility. Further, the association between horizontal transfer ability and resistance to β-lactams, the first-choice drugs for H. influenzae infection, was investigated. The transformation efficiency of 50 clinical isolates varied widely, ranging from 102 to 106 colony forming unit (CFU) of the colonies obtained by horizontal transfer assay. Efficiency was associated with β-lactam resistance caused by ftsI mutations, indicating that strains with high horizontal transfer ability acquired quinolone low-susceptibility as well as β-lactam resistance more easily. Strains with high transformation efficiency increased the transcript level of comA, suggesting that enhanced com operon was associated with a high DNA uptake ability. Overall, this study revealed that the transformation ability of H. influenzae was associated with multiple antimicrobial resistance. Increase in the number of strains with high horizontal transformation ability has raised concerns regarding the rapid spread of antimicrobial-resistant H. influenzae.
Insights
Horizontal gene transfer in Haemophilus influenzae increases resistance to multiple antimicrobial agents, including quinolones and beta-lactams. This enhanced transformation ability raises concerns about the spread of antimicrobial resistance.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- Increasing prevalence of quinolone low-susceptible Haemophilus influenzae in Japan.
- Low quinolone susceptibility arises from target gene mutations or horizontal gene transfer via natural transformation.
- Need to investigate the link between horizontal gene transfer and resistance to other antimicrobial agents.
Purpose of the Study:
- To examine the association between horizontal gene transfer ability and resistance to quinolones and beta-lactams in Haemophilus influenzae.
- To quantify horizontal transfer ability using experimental transfer assays.
- To investigate the role of the com operon in DNA uptake.
Main Methods:
- Experimental transfer assay to quantify horizontal transfer ability in 50 clinical isolates of Haemophilus influenzae.
- Investigation of the association between transformation efficiency and resistance to beta-lactams.
- Analysis of comA transcript levels in strains with high transformation efficiency.
Main Results:
- Transformation efficiency varied widely (10^2 to 10^6 CFU) among isolates.
- High horizontal transfer ability was associated with beta-lactam resistance due to ftsI mutations.
- Strains with high transformation efficiency showed increased comA transcript levels, suggesting enhanced DNA uptake.
- Horizontal transfer ability correlated with multiple antimicrobial resistance.
Conclusions:
- Transformation ability of Haemophilus influenzae is linked to multiple antimicrobial resistance.
- Increased prevalence of strains with high horizontal transfer ability facilitates the spread of antimicrobial resistance.
- Enhanced com operon activity contributes to high DNA uptake ability.
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