Genetic basis of multidrug resistance in Acinetobacter clinical isolates in Taiwan
Yu-Chi Lin1, Ko-Chiang Hsia, Yee-Chun Chen
1Research and Diagnostic Center, Centers for Disease Control, Taipei, Taiwan.
Abstract:
Multidrug-resistant (MDR) Acinetobacter spp. have emerged as a threat to public health. We investigated the various genes involved in resistance to fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems in 75 clinical Acinetobacter isolates from a Taiwanese hospital. All isolates were tested for the gyrA mutations, the presence of integrons, bla(AmpC), and carbapenem resistance genes. The Ser83Leu mutation in GyrA accounted for fluoroquinolone resistance. The presence of integrons containing aminoglycoside-modifying enzymes was associated with resistance to gentamicin and tobramycin but not with resistance to amikacin. The presence of an ISAba1 element upstream of bla(AmpC) was correlated with cephalosporin resistance. Although most Acinetobacter baumannii isolates with ISAba1-bla(OXA-51-)(like) were resistant to carbapenems, several isolates remained susceptible to carbapenems. Transformation by the introduction of ISAba1-bla(OXA-23) or ISAba1-bla(OXA-66) into A. baumannii ATCC 15151 (CIP 70.10), resulting in the overexpression of OXA-23 or OXA-66, respectively, suggested the role of the ISAba1 element as a strong promoter. The two transformants showed significantly increased resistance to piperacillin-tazobactam, imipenem, and meropenem. The cefepime resistance conferred by ISAba1-bla(OXA-23) and the impact of ISAba1-bla(OXA-66) on carbapenem resistance in A. baumannii are reported here for the first time. Continuous surveillance of antibiotic resistance genes in MDR Acinetobacter spp. and elucidation of their antibiotic resistance mechanisms are crucial for the development of therapy regimens and for the prevention of further dissemination of these antibiotic resistance genes.
Insights
Multidrug-resistant Acinetobacter species pose a public health threat. This study identified key resistance genes, including gyrA mutations and ISAba1-bla elements, crucial for understanding and combating antibiotic resistance in Acinetobacter baumannii.
Area of Science:
- Microbiology
- Molecular Biology
- Public Health
Background:
- Multidrug-resistant (MDR) Acinetobacter spp. are a significant global health concern.
- Understanding the genetic basis of antibiotic resistance in these pathogens is critical for effective treatment strategies.
Purpose of the Study:
- To investigate the genetic mechanisms conferring resistance to fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems in clinical Acinetobacter isolates.
- To elucidate the role of specific genes and mobile genetic elements in multidrug resistance.
Main Methods:
- Analysis of 75 clinical Acinetobacter isolates from Taiwan.
- Testing for gyrA mutations, integrons, bla(AmpC), and carbapenem resistance genes.
- Experimental transformation to assess the function of ISAba1-bla elements.
Main Results:
- Fluoroquinolone resistance was linked to the Ser83Leu mutation in GyrA.
- Integrons correlated with resistance to gentamicin and tobramycin, but not amikacin.
- ISAba1 element upstream of bla(AmpC) was associated with cephalosporin resistance.
- ISAba1-bla(OXA-23) and ISAba1-bla(OXA-66) conferred resistance to carbapenems and piperacillin-tazobactam.
- The ISAba1 element acts as a strong promoter for resistance gene expression.
Conclusions:
- Specific genetic mutations and the ISAba1 element play key roles in the multidrug resistance of Acinetobacter spp.
- The findings highlight the importance of continuous surveillance and understanding resistance mechanisms for developing new therapies and preventing spread.
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