Global Clone-Specific Resistomes Explored in Clinical Isolates Recovered from Egypt.

() is a highly problematic pathogen with an enormous capacity to acquire or upregulate antibiotic drug resistance determinants. The genomic epidemiology and resistome structure of 46 clinical isolates were studied using whole-genome sequencing. The isolates were chosen based on reduced susceptibility to at least three classes of antimicrobial compounds and were initially identified using MALDI-TOF/MS, followed by polymerase chain reaction amplification of genes. The susceptibility profiles were determined using a broth microdilution assay. Multi-, extensive-, and pan-drug resistance was shown by 34.8%, 63.0%, and 2.2% of the isolates, respectively. These were most susceptible to colistin (95.7%), amikacin, and trimethoprim/sulfamethoxazole (32.6% each), while only 26.1% of isolates were susceptible to tigecycline. In silico multi-locus sequence typing revealed 8 Pasteur and 22 Oxford sequence types (STs) including four novel STs (ST 2805, 2806, 2807, and 2808). The majority of the isolates belonged to Global Clone (GC) 2 (76.4%), GC5 (19.6%), GC4 (6.5%), GC9 (4.3%), and GC7 (2.2%) lineages. An extensive resistome potentially conferring resistance to the majority of the tested antimicrobials was identified in silico. Of all known carbapenem resistance genes, was carried by most of the isolates (69.6%), followed by IS-amplified (56.5%), and (21.7% each), and (2.2%) genes. A significant correlation was found between carbapenem resistance and mutations, which were evident in 35 (76.0%) isolates. A lower proportion of carbapenem resistance was noted for strains possessing both - and . Amikacin resistance was most probably mediated by , , and , most commonly coexisting in GC2 isolates. No mutations were found in or operons in the colistin-resistant isolates. Tigecycline resistance was associated with (N268Y) and (A436T) mutations. While the lineage-specific distribution of some genes (e.g., and alleles) was evident, some resistance genes, such as and , were found in all GCs. The data generated here highlight the contribution of five GCs in infections in Egypt and enable the comprehensive analysis of GC-specific resistomes, thus revealing the dissemination of the carbapenem resistance gene in isolates encompassing all GCs.