Evolution of mutations in the ftsI gene leading to amino acid substitutions in PBP3 in Haemophilus influenzae strains under the selective pressure of ampicillin and cefuroxime

Background: Aminopenicillins are recommended agents for non-invasive Haemophilus influenzae infections. One of the mechanisms of resistance to β-lactams is the alteration of the transpeptidase region of penicillin binding protein 3 (PBP3) which is caused by mutations in the ftsI gene. It was shown t...

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Main Authors: Vladislav Jakubu (Author), Iveta Vrbova (Author), Ibrahim Bitar (Author), Marketa Cechova (Author), Lucia Malisova (Author), Helena Zemlickova (Author)
Format: Book
Published: Elsevier, 2024-09-01T00:00:00Z.
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001 doaj_00d71c6d4dcd426eaace2d1a2f2b2f5b
042 |a dc 
100 1 0 |a Vladislav Jakubu  |e author 
700 1 0 |a Iveta Vrbova  |e author 
700 1 0 |a Ibrahim Bitar  |e author 
700 1 0 |a Marketa Cechova  |e author 
700 1 0 |a Lucia Malisova  |e author 
700 1 0 |a Helena Zemlickova  |e author 
245 0 0 |a Evolution of mutations in the ftsI gene leading to amino acid substitutions in PBP3 in Haemophilus influenzae strains under the selective pressure of ampicillin and cefuroxime 
260 |b Elsevier,   |c 2024-09-01T00:00:00Z. 
500 |a 1438-4221 
500 |a 10.1016/j.ijmm.2024.151626 
520 |a Background: Aminopenicillins are recommended agents for non-invasive Haemophilus influenzae infections. One of the mechanisms of resistance to β-lactams is the alteration of the transpeptidase region of penicillin binding protein 3 (PBP3) which is caused by mutations in the ftsI gene. It was shown that exposure to beta-lactams has a stimulating effect on increase of prevalence of H. influenzae strains with the non-enzymatic mechanism of resistance. Objectives: The aim of our study was to compare the mutational potential of ampicillin and cefuroxime in H. influenzae strains, determination of minimum inhibitory concentration and the evolution of mutations over time, focusing on amino acid substitutions in PBP3. Methods: 30 days of serial passaging of strains in liquid broth containing increasing concentrations of ampicillin or cefuroxime was followed by whole-genome sequencing. Results: On average, cefuroxime increased the minimum inhibitory concentration more than ampicillin. The minimum inhibitory concentration was increased by a maximum of 32 fold. Substitutions in the PBP3 started to appear after 15 days of passaging. In PBP3, cefuroxime caused different substitutions than ampicillin. Conclusions: Our experiment observed differences in mutation selection by ampicillin and cefuroxime. Selection pressure of antibiotics in vitro generated substitutions that do not occur in clinical strains in the Czech Republic. 
546 |a EN 
690 |a Ampicillin 
690 |a Cefuroxime 
690 |a Haemophilus 
690 |a PBP3 
690 |a WGS 
690 |a Microbiology 
690 |a QR1-502 
690 |a Other systems of medicine 
690 |a RZ201-999 
655 7 |a article  |2 local 
786 0 |n International Journal of Medical Microbiology, Vol 316, Iss , Pp 151626- (2024) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S1438422124000304 
787 0 |n https://doaj.org/toc/1438-4221 
856 4 1 |u https://doaj.org/article/00d71c6d4dcd426eaace2d1a2f2b2f5b  |z Connect to this object online.