Analysis of blaCHDL Genes and Insertion Sequences Related to Carbapenem Resistance in Acinetobacter baumannii Clinical Strains Isolated in Warsaw, Poland

Alicja Słoczyńska,Stefan Tyski,Agnieszka E Laudy,Matthew E Wand

doi:10.3390/ijms22052486

Abstract

Acinetobacter baumannii is an important cause of nosocomial infections worldwide. The elucidation of the carbapenem resistance mechanisms of hospital strains is necessary for the effective treatment and prevention of resistance gene transmission. The main mechanism of carbapenem resistance in A. baumannii is carbapenemases, whose expressions are affected by the presence of insertion sequences (ISs) upstream of blaCHDL genes. In this study, 61 imipenem-nonsusceptible A. baumannii isolates were characterized using phenotypic (drug-susceptibility profile using CarbaAcineto NP) and molecular methods. Pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) methods were utilized for the genotyping. The majority of isolates (59/61) carried one of the following acquired blaCHDL genes: blaOXA-24-like (39/59), ISAba1-blaOXA-23-like (14/59) or ISAba3-blaOXA-58-like (6/59). Whole genome sequence analysis of 15 selected isolates identified the following intrinsic blaOXA-66 (OXA-51-like; n = 15) and acquired class D β-lactamases (CHDLs): ISAba1-blaOXA-23 (OXA-23-like; n = 7), ISAba3-blaOXA-58-ISAba3 (OXA-58-like; n = 2) and blaOXA-72 (OXA-24-like; n = 6). The isolates were classified into 21 pulsotypes using PFGE, and the representative 15 isolates were found to belong to sequence type ST2 of the Pasteur MLST scheme from the global IC2 clone. The Oxford MLST scheme revealed the diversity among these studied isolates, and identified five sequence types (ST195, ST208, ST208/ST1806, ST348 and ST425). CHDL-type carbapenemases and insertion elements upstream of the blaCHDL genes were found to be widespread among Polish A. baumannii clinical isolates, and this contributed to their carbapenem resistance.

Highlights

IntroductionIn February 2017, the World Health Organization (WHO) published a list of the antibiotic-resistant “priority pathogens” that pose the greatest threat to human health [1]
In February 2017, the World Health Organization (WHO) published a list of the antibiotic-resistant “priority pathogens” that pose the greatest threat to human health [1].Carbapenem-resistant Acinetobacter baumannii was classified as the most pressing threat in “the critical group”
PCR analysis of the blaCHDL genes occurrence among these isolates revealed the presence of intrinsic blaOXA-51-like genes and following acquired blaCHDL genes: blaOXA-23-like in 14 of the 61 (23%) isolates, blaOXA-24-like in 39 of the 61 (64%) isolates and blaOXA-58-like in 6 of the 61 (10%) isolates

Summary

Introduction

In February 2017, the World Health Organization (WHO) published a list of the antibiotic-resistant “priority pathogens” that pose the greatest threat to human health [1]. Carbapenem-resistant Acinetobacter baumannii was classified as the most pressing threat in “the critical group”. This non-fermentative, Gram-negative coccobacillus is one of the main causes of severe nosocomial infections, such as ventilator-associated pneumonia, bloodstream infections, bacteremia, urinary tract infections and wound infections, especially in burn patients and post-surgical procedures [2,3]. The increased incidence of carbapenem resistance among clinical isolates, which has risen dramatically over the last twenty years, is of major concern.

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