Hamed Samira M, Elkhatib Walid F, Brangsch Hanka, Gesraha Ahmed S, Moustafa Shawky, Khater Dalia F, Pletz Mathias W, Sprague Lisa D, Neubauer Heinrich, Wareth Gamal
Department of Microbiology and Immunology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza 12451, Egypt.
Microbiology and Immunology Department, Faculty of Pharmacy, Ain Shams University, African Union Organization Street, Cairo 11566, Egypt.
Antibiotics (Basel). 2023 Jul 4;12(7):1149. doi: 10.3390/antibiotics12071149.
() 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.
（）是一种极具问题的病原体，具有获取或上调抗生素耐药决定因素的巨大能力。使用全基因组测序研究了46株临床分离株的基因组流行病学和耐药基因组结构。这些分离株是根据对至少三类抗菌化合物敏感性降低而选择的，最初使用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF/MS）进行鉴定，随后通过基因的聚合酶链反应扩增。使用肉汤微量稀释法测定药敏谱。分别有34.8%、63.0%和2.2%的分离株表现出多重耐药、广泛耐药和泛耐药。这些分离株对黏菌素（95.7%）、阿米卡星和甲氧苄啶/磺胺甲恶唑（各32.6%）最敏感，而只有26.1%的分离株对替加环素敏感。计算机多位点序列分型揭示了8种巴斯德和22种牛津序列类型（STs），包括4种新的STs（ST 2805、2806、2807和2808）。大多数分离株属于全球克隆（GC）2（76.4%）、GC5（19.6%）、GC4（6.5%）、GC9（4.3%）和GC7（2.2%）谱系。在计算机上鉴定出一个广泛的耐药基因组，可能赋予对大多数测试抗菌药物的耐药性。在所有已知的碳青霉烯耐药基因中，大多数分离株（69.6%）携带，其次是IS扩增的（56.5%）、和（各21.7%）以及（2.2%）基因。发现碳青霉烯耐药与突变之间存在显著相关性，在35株（76.0%）分离株中很明显。同时拥有和的菌株碳青霉烯耐药比例较低。阿米卡星耐药最可能由、和介导，最常见于GC2分离株中。在耐黏菌素的分离株中未发现或操纵子中的突变。替加环素耐药与（N268Y）和（A436T）突变有关。虽然一些基因（如和等位基因）的谱系特异性分布很明显，但一些耐药基因，如和，在所有GC中都有发现。这里生成的数据突出了五个GC在埃及感染中的作用，并能够对GC特异性耐药基因组进行全面分析，从而揭示碳青霉烯耐药基因在涵盖所有GC的分离株中的传播情况。
