Maghembe Reuben S, Magulye Maximilian A K, Eilu Emmanuel, Sekyanzi Simon, Mwesigwa Savannah, Katagirya Eric
Department of Microbiologgy and Immunology, Faculty of Biomedical Sciences, Kampala International University, Western Campus, Ishaka, Uganda.
Department of Health and Biomedical Sciences, Didia Education and Health Organization, P. O. Box 113, Shinyanga, Tanzania.
Heliyon. 2024 Apr 26;10(9):e30187. doi: 10.1016/j.heliyon.2024.e30187. eCollection 2024 May 15.
Sepsis and drug resistance represent a complex of the most common global causes of mortality in intensive care units (ICUs) especially among patients with comorbidities. Extraintestinal pathogenic (ExPEC) strains are highly implicated in systemic infections, with multidrug resistance exacerbating the risk of chronic conditions and patient mortality. The diversity of virulence and evolution of multidrug resistance are yet to be fully deciphered. In this work, we aimed at unveiling the pathogens and their genomic determinants of virulence and drug resistance relevant to increased sepsis in a sickle cell child admitted to ICU. From a rectal swab, we isolated a strain of from the patient and phenotypically tested it against a panel of selected beta lactams, fluoroquinolones, macrolides, aminoglycosides and colistin. We then sequenced the entire genome and integrated multiple bioinformatic pipelines to divulge the virulence and multidrug resistance profiles of the isolate. Our results revealed that the isolate belongs to the sequence type (ST) 58/24, which (ST58), is a known ExPEC. With the use of PathogenFinder, we were able to confirm that this isolate is a human pathogen (p = 0.936). The assembled chromosome and two plasmids encode virulence factors related to capsule (antiphagocytosis), serum survival and resistance, type 6 secretion system (T6SS), multiple siderophores (iron acquisition), and biosynthetic gene clusters for polyketides and nonribosomal peptides exhibiting host cell damaging activity . The genome also harbors multidrug resistance genotypes including extended spectrum beta lactamase (ESBL) genes such as 1A/B, sulfonamide resistance genes , fluoroquinolone resistance genes and nonsynonymous mutations of the gene , conferring intrinsic colistin resistance. Conclusively, this pathogen holds the potential to cause systemic infection and might exacerbate sickle cell anemia in the patient. The virulence and multidrug resistance profiles are encoded by both the chromosome and plasmids. Genomic surveillance of pathogens with multidrug resistance among patients with commodities is crucial for effective disease management.
脓毒症和耐药性是重症监护病房（ICU）中最常见的全球死亡原因组合，在患有合并症的患者中尤为如此。肠外致病性（ExPEC）菌株与全身感染高度相关，多重耐药性加剧了慢性病风险和患者死亡率。毒力多样性和多重耐药性的演变尚未完全阐明。在这项工作中，我们旨在揭示与入住ICU的镰状细胞病患儿脓毒症增加相关的病原体及其毒力和耐药性的基因组决定因素。从直肠拭子中，我们从患者身上分离出一株菌株，并对其进行表型测试，以检测一组选定的β-内酰胺类、氟喹诺酮类、大环内酯类、氨基糖苷类和黏菌素。然后，我们对整个基因组进行测序，并整合多个生物信息学管道，以揭示分离株的毒力和多重耐药性特征。我们的结果表明，该分离株属于序列型（ST）58/24，其中（ST58）是一种已知的ExPEC。使用PathogenFinder，我们能够确认该分离株是一种人类病原体（p = 0.936）。组装的染色体和两个质粒编码与荚膜（抗吞噬作用）、血清存活和抗性、6型分泌系统（T6SS）、多种铁载体（铁获取）以及具有宿主细胞损伤活性的聚酮化合物和非核糖体肽的生物合成基因簇相关的毒力因子。该基因组还含有多重耐药基因型，包括超广谱β-内酰胺酶（ESBL）基因，如1A/B、磺胺耐药基因、氟喹诺酮耐药基因和基因的非同义突变，赋予内在的黏菌素耐药性。总之，这种病原体有可能引起全身感染，并可能使患者的镰状细胞贫血恶化。毒力和多重耐药性特征由染色体和质粒编码。对患有合并症患者中具有多重耐药性的病原体进行基因组监测对于有效的疾病管理至关重要。
