Highly carbapenem-resistant Achromobacter xylosoxidans harboring blaNDM-1 in Myanmar

Abstract

Achromobacter xylosoxidans is a multidrug-resistant, non-glucose-fermenting, gram-negative bacterium with intrinsic resistance to many antimicrobial agents. Between 2016 and 2017, five A. xylosoxidans isolates were obtained from five patients at three hospitals in Myanmar. Minimum inhibitory concentrations (MICs) against various antimicrobial agents were determined using the microdilution method. Whole genome sequencing was performed with the MiSeq and MinION platforms. Resistance genes and their surrounding structures were identified and compared. All five isolates were resistant to amikacin and aztreonam. Among them, one isolate, MyNCGM749, was resistant to imipenem and meropenem with MICs of 256 µg/mL and amikacin with MIC of >512 µg/mL but intermediate to ciprofloxacin with MIC of 2 µg/mL. The isolate carried bla_NDM-1 encoding metallo-β-lactamase, bla_PSE-1 encoding extended-spectrum-β-lactamase, and bla_OXA-114 (encoding intrinsic -β-lactamase present in A. xylosoxidans), along with five aminoglycoside modification encoding genes including aac(6')-Ib, aph (6)-Id, aph(3'')-Ib, ant(4')-Iib, and aph(3')-VI on its chromosome. The genetic structure surrounding bla_NDM-1 contained four IS91 elements identical to those found in carbapenem-resistant Pseudomonas asiatica isolates in Myanmar. This is the first report of A. xylosoxidans in Myanmar. Although A. xylosoxidans harboring bla_NDM-1 has been reported in a single strain from India, its genomic details have not been previously described. This study indicates that the bla_NDM-1-containing structure flanked by IS91 is spreading among gram-negative, non-glucose-fermenting bacteria in Myanmar and neighboring countries.IMPORTANCEAchromobacter species were originally environmental organisms that became opportunistic pathogens with multidrug resistance. Achromobacter xylosoxidans is associated with nosocomially acquired infections affecting multiple organ systems, including the respiratory and urinary tracts, and, less commonly, the cardiovascular and central nervous systems. To date, carbapenem-resistant A. xylosoxidans carrying carbapenemase-encoding genes has been reported in several countries, including Greece, India, Italy, Japan, Korea, Libya, and the Netherlands. In this molecular epidemiological study on A. xylosoxidans in Myanmar, we identified the genomic structure surrounding bla_NDM-1, flanked by IS91. This structure may facilitate the spread of non-glucose-fermenting gram-negative bacteria, such as Achromobacter, Pseudomonas, and Stenotrophomonas species, in Asian countries.

Keywords: Achromobacter xylosoxidans; blaNDM-1; carbapenemase; multidrug resistance.

Fig 1

Genomic environments surrounding bla_NDM-1 in A. xylosoxidans MyNCGM152. The genetic environment of bla_NDM-1 in MyNCGM749 closely resembled those observed in clinical isolates of P. asiatica from Myanmar and an environmental isolate of S. acidaminiphila from Bangladesh. Abbreviations: orf1: gene encoding hypothetical protein, orf2: gene encoding CPBP family intramembrane glutamic endopeptidase, orf3: gene encoding ABC transporter ATP-binding protein, orf4: gene encoding hypothetical protein, orf5: gene encoding hypothetical protein, orf6: gene encoding glutathione S-transferase N-terminal domain-containing protein, orf7: gene encoding hypothetical protein, orf8: gene encoding DNA repair ATPase, orf9: gene encoding nucleotidyltransferase domain-containing protein, and orf10: gene encoding multicopper oxidase domain-containing protein.

Fig 2

Molecular phylogenetic tree of A. xylosoxidans strains based on whole genome sequences. The tree includes 39 strains collected from several countries, including Australia, Argentina, Canada, China, France, Germany, India, Japan, Nigeria, Oman, Russia, Serbia, Thailand, the United Kingdom, and the United States. The five strains tested in this study, obtained from Myanmar, are highlighted in gray. Asterisk (*) indicates a pair of strains with the furthest distance. Asterisks (**) indicate with the closest distance.