Abstract

Resistance to the last-line antibiotics against invasive Gram-negative bacterial infection is a rising concern in public health. Multidrug resistant (MDR) Acinetobacter baumannii Aci46 can resist colistin and carbapenems with a minimum inhibitory concentration of 512 µg/mL as determined by microdilution method and shows no zone of inhibition by disk diffusion method. These phenotypic characteristics prompted us to further investigate the genotypic characteristics of Aci46. Next generation sequencing was applied in this study to obtain whole genome data. We determined that Aci46 belongs to Pasture ST2 and is phylogenetically clustered with international clone (IC) II as the predominant strain in Thailand. Interestingly, Aci46 is identical to Oxford ST1962 that previously has never been isolated in Thailand. Two plasmids were identified (pAci46a and pAci46b), neither of which harbors any antibiotic resistance genes but pAci46a carries a conjugational system (type 4 secretion system or T4SS). Comparative genomics with other polymyxin and carbapenem-resistant A. baumannii strains (AC30 and R14) identified shared features such as CzcCBA, encoding a cobalt/zinc/cadmium efflux RND transporter, as well as a drug transporter with a possible role in colistin and/or carbapenem resistance in A. baumannii. Single nucleotide polymorphism (SNP) analyses against MDR ACICU strain showed three novel mutations i.e., Glu229Asp, Pro200Leu, and Ala138Thr, in the polymyxin resistance component, PmrB. Overall, this study focused on Aci46 whole genome data analysis, its correlation with antibiotic resistance phenotypes, and the presence of potential virulence associated factors.

Highlights

  • Acinetobacter baumannii is an opportunistic pathogenic bacterium that causes nosocomial infections in immunocompromised patients, especially patients treated in the intensive care unit (ICU) [1,2]

  • We found that Aci46 was resistant to all twenty drugs (Table 1, Figure S1 and Supplement Table S1) with a minimum inhibitory concentration (MIC) for colistin of 512 μg/mL (Figure 1)

  • We have demonstrated that Aci46 is an XDR strain according to the definition described by Magiorakos et al [4]

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Summary

Introduction

Acinetobacter baumannii is an opportunistic pathogenic bacterium that causes nosocomial infections in immunocompromised patients, especially patients treated in the intensive care unit (ICU) [1,2]. A. baumannii infections usually occur following: trauma, surgery, catheterization, or endotracheal intubation [3]. This bacterium is well known for its multidrug resistant (MDR) characteristics, defined as resistance to at least one agent in three or more antibiotic categories [4], and as a nosocomial ESKAPE pathogen, a group including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa, and Enterobacter species [5]. Presence of the carbapenemase encoding genes, blaOXA-23 or blaOXA-51, in combination with insertion sequence elements is frequently found in CRAB [11]

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