Dynamic Gene Clusters Mediating Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates

Abstract

Acinetobacter baumanni (A. baumannii), a nonfermenting Gram-negative bacterium, has recently been associated with a broad range of nosocomial infections. To gain more meaningful insight into the problem of nosocomial illnesses caused by the multidrug-resistant (MDR) A. baumannii, as well as the factors that increase the risk of catching these infections, this investigation included a total of 86 clinical A. baumannii infections. Repetitive extragenic palindromic (REP)-PCR was used to investigate imipenem-resistant A. baumannii isolates for dynamic gene clusters causing carbapenem resistance. Four distinct A. baumannii lineages were found in the REP-PCR-DNA fingerprints of all isolates, with 95% of the samples coming from two dominant lineages. Imipenem, amikacin, and ciprofloxacin were less effective against genotype (A) isolates because of enhanced antibiotic tolerance. Lastly, to gain more insight into the mode of action of imipenem, we explored the binding affinity of imipenem toward different Acinetobacter baumannii OXA beta-lactamase class enzymes.

Keywords: Acinetobacter baumannii; carbapenem-resistant; dynamic gene; imipenem; nosocomial infection; repetitive extragenic palindromic.

Figure 1

Acinetobacter baumannii relationships are depicted in this dendrogram. Using the unweighted pair group method of arithmetic averages of Acinetobacter baumannii REP-PCR DNA fingerprints, the dendrogram was built. Imipenem resistance profiles, Acinetobacter isolates, and REP-PCR fingerprints are all displayed. The dotted vertical line indicates the 90% similarity threshold.

Figure 2

The 2D and 3D molecular docking interactions of imipenem (green in 3D interactions) with OXA proteins: OXA-23 (A), OXA-48 (B), OXA-23 A220 (C), OXA-24 (D), OXA-143 (E), OXA-655 (F), OXA-10 (G), and OXA-51 (H). The hydrogen bonds are illustrated as dotted blue arrows; (C atoms, green; S atoms, yellow; O atoms, red).

Figure 2

The 2D and 3D molecular docking interactions of imipenem (green in 3D interactions) with OXA proteins: OXA-23 (A), OXA-48 (B), OXA-23 A220 (C), OXA-24 (D), OXA-143 (E), OXA-655 (F), OXA-10 (G), and OXA-51 (H). The hydrogen bonds are illustrated as dotted blue arrows; (C atoms, green; S atoms, yellow; O atoms, red).

Figure 2

The 2D and 3D molecular docking interactions of imipenem (green in 3D interactions) with OXA proteins: OXA-23 (A), OXA-48 (B), OXA-23 A220 (C), OXA-24 (D), OXA-143 (E), OXA-655 (F), OXA-10 (G), and OXA-51 (H). The hydrogen bonds are illustrated as dotted blue arrows; (C atoms, green; S atoms, yellow; O atoms, red).