The innate resistome of “recalcitrant” Acinetobacter baumannii and the role of nanoparticles in combating these MDR pathogens

Abstract

Acinetobacter baumannii, a nosocomial pathogen, and member of ESKAPE bacteria are currently a global threat. A. baumannii is equipped naturally laden with strong intrinsic resistance factors and is also capable of acquiring many resistance determinants against different antibiotic classes. Intrinsic resistome is defined as a mechanism of antibiotic resistance that is innately expressed/chromosomally encoded, irrespective of prior antibiotic exposure. Although these innate resistance factors are themselves poorly effective in conferring a high-level resistance, together with other resistance factors their force can be large enough to confer an organism multidrug resistant (MDR). In A. baumannii, which are predominantly of environmental origin (an opportunistic pathogen), weight on the impact of extreme resistance and evolution is often laid on their intrinsic antibiotic resistance phenotype. This review is focused on emphasizing the role of intrinsic resistome involved in the antibiotic resistance of A. baumannii, the understanding of which will be very helpful in combating this opportunistic pathogen. With a dead-end in the treatment of infections due to MDR A. baumannii, different avenues have to be explored for a better treatment option. This review will also discuss the application of nanoparticles as antimicrobials and as a conjugate for restoring the bioactivity of the available drugs against MDR pathogens.

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Fig. 1

Abbreviations

ESKAPE:

Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species

MDR:

Multidrug-resistant

XDR:

Extensive drug-resistant

PDR:

Pan-drug resistant

BAP:

Biofilm-associated protein

LPS:

Lipopolysaccharides

OMVs:

Outer membrane vesicles

PBP:

Penicillin-binding proteins

ADC:

Acinetobacter-derived cephalosporinases

RND:

Resistance nodulation division

CRAB:

Carbapenem-resistant

MBL:

Metallo β-lactamase

CHDLs:

Chromosomally mediated carbapenem hydrolyzing oxacillinase

OMPs:

Outer membrane proteins

CarO:

Carbapenem resistance-associated Omp

MFS:

Major facilitator superfamily

MATE:

Multidrug and toxic compound extrusion

QRDRs:

Quinolone resistance-determining regions

NP:

Nanoparticles

ROS:

Reactive-oxygen species

Ag:

Silver, Au- Gold, CeO2-cerium oxide nanoparticles

FeO:

Ferrous oxide

Cu:

Copper

NiO:

Nickle oxide

ZnO:

Zinc oxide

TiO2 :

Titanium dioxide

Al2O3 :

Aluminium oxide

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Funding

National Natural Science Foundation of China (grant no.81771756). The Postdoctoral Foundation of Jiangsu Province (grant no.1601002C).

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Aparna Vasudevan and Dineshkumar Kesavan wrote the manuscript. Zhaoliang Su critically reviewed and edited the manuscript. Shengjun Wang revised for its integrity and accuracy. Huaxi Xu approved the final version of this manuscript and takes responsibility for its contents.

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Correspondence to Huaxi Xu.

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Aparna, V., Dineshkumar, K., Su, Z. et al. The innate resistome of “recalcitrant” Acinetobacter baumannii and the role of nanoparticles in combating these MDR pathogens. Appl Nanosci (2021). https://doi.org/10.1007/s13204-021-01877-6

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Keywords

  • Acinetobacter baumannii
  • Intrinsic resistome
  • Outer membrane permeability
  • Drug efflux pumps
  • β-Lactamases
  • Nanoparticles
  • Conjugate drugs