Diversity of carbapenem-resistant Acinetobacter baumannii and bacteriophage-mediated spread of the Oxa23 carbapenemase

Abstract

Carbapenem-resistant Acinetobacter baumannii are prevalent in low- and middle-income countries such as Egypt, but little is known about the molecular epidemiology and mechanisms of resistance in these settings. Here, we characterize carbapenem-resistant A. baumannii from Alexandria, Egypt, and place it in a regional context. Fifty-four carbapenem-resistant isolates from Alexandria Main University Hospital (AMUH), Alexandria, Egypt, collected between 2010 and 2015 were genome sequenced using Illumina technology. Genomes were de novo assembled and annotated. Genomes for 36 isolates from the Middle East region were downloaded from GenBank. The core-gene compliment was determined using Roary, and analyses of recombination were performed in Gubbins. Multilocus sequence typing (MLST) sequence type (ST) and antibiotic-resistance genes were identified. The majority of Egyptian isolates belonged to one of three major clades, corresponding to Pasteur MLST clonal complex (CCPAS) 1, CCPAS2 and STPAS158. Strains belonging to STPAS158 have been reported almost exclusively from North Africa, the Middle East and Pakistan, and may represent a region-specific lineage. All isolates carried an oxa23 gene, six carried bla NDM-1 and one carried bla NDM-2. The oxa23 gene was located on a variety of different mobile elements, with Tn2006 predominant in CCPAS2 strains, and Tn2008 predominant in other lineages. Of particular concern, in 8 of the 13 CCPAS1 strains, the oxa23 gene was located in a temperate bacteriophage phiOXA, previously identified only once before in a CCPAS1 clone from the USA military. The carbapenem-resistant A. baumannii population in AMUH is very diverse, and indicates an endemic circulating population, including a region-specific lineage. A major mechanism for oxa23 dissemination in CCPAS1 isolates appears to be a bacteriophage, presenting new concerns about the ability of these carbapenemases to spread throughout the bacterial population.

Mobile genetic elements in Acinetobacter antibiotic‐resistance acquisition and dissemination

“…Numerous studies since have identified a relationship between IS Aba1 insertion upstream of bla OXA‐23 and carbapenem resistance, and IS insertion is often part of a composite transposon structure as previously reviewed 80 and discussed below. IS Aba4 has also been reported to activate bla OXA‐23 expression in isolates from Algeria and France 81 and was similarly found adjacent to bla OXA‐23 in an isolate from Egypt 82 . Together, these studies suggest that IS‐mediated enhancement of expression is required for bla OXA‐23 to confer carbapenem resistance.…”

“…However, another study in China showed that the majority of bla OXA‐23 was found within Tn 2006 , 112 suggesting that there can be significant variability within a geographic region. In a concerning finding, sequencing of A. baumannii isolates from Egypt identified the presence of bla OXA‐23 in these composite transposon structures, one of which was inserted in the prophage phiOXA‐A35 in 6/54 strains 82 . PhiOXA‐A35 is identical to a prophage in A. baumannii ABUW‐5075 113 that was originally isolated in the United States, 114 demonstrating that the prophage has been found in multiple geographic areas.…”

Streptococcus pyogenes Φ1207.3 Is a Temperate Bacteriophage Carrying the Macrolide Resistance Gene Pair mef (A)- msr (D) and Capable of Lysogenizing Different Streptococci

“…Prophages play an important role in shaping the S. pyogenes genome, affecting the physiology and pathogenesis of this organism. Prophages are rarely found to directly encode antimicrobial resistance genes, and their transfer seldom occurs between different bacterial species ( 9 , 25 , 26 ). In S. pyogenes , the macrolide efflux genes mef (A)- msr (D) were found associated with several prophages, including Φ1207.3, Φ10394.4, Φ29862, Φ29961, Φ29854, and Φm46.1 and its variant, VP_00501.1 ( 15 , 16 , 18 , 19 ).…”

Emergence of uncommon KL38-OCL6-ST220 carbapenem-resistant Acinetobacter pittii strain, co-producing chromosomal NDM-1 and OXA-820 carbapenemases

“…A previous study from Krahn et al (2016) demonstrated that transposon Tn125, which embedded the bla NDM-1 gene, could transfer via phage-mediated transduction within the species of A. baumannii. Thus, prophages may play a key role in the horizontal gene transfer (HGT) of carbapenems resistance genes, such as bla NDM-1 and bla OXA-23 (Krahn et al, 2016;Abouelfetouh et al, 2022). Another study from Loh et al (2020) in China showed a wide variation in the number of prophages in A. baumannii genomes.…”