Chromosomal and plasmid-encoded virulence and multidrug resistance of Escherichia coli ST58/24 infecting a 2-year-old sickle cell patient with sepsis in Kampala Uganda, East Africa

Reuben S Maghembe; Maximilian A K Magulye; Emmanuel Eilu; Simon Sekyanzi; Savannah Mwesigwa; Eric Katagirya

doi:10.1016/j.heliyon.2024.e30187

Chromosomal and plasmid-encoded virulence and multidrug resistance of Escherichia coli ST58/24 infecting a 2-year-old sickle cell patient with sepsis in Kampala Uganda, East Africa

Heliyon. 2024 Apr 26;10(9):e30187. doi: 10.1016/j.heliyon.2024.e30187. eCollection 2024 May 15.

Authors

Reuben S Maghembe^{1

2

3

4

5}, Maximilian A K Magulye^{2

5}, Emmanuel Eilu¹, Simon Sekyanzi⁶, Savannah Mwesigwa⁵, Eric Katagirya⁵

Affiliations

¹ Department of Microbiologgy and Immunology, Faculty of Biomedical Sciences, Kampala International University, Western Campus, Ishaka, Uganda.
² Department of Health and Biomedical Sciences, Didia Education and Health Organization, P. O. Box 113, Shinyanga, Tanzania.
³ Biological and Marine Sciences Unit, Faculty of Natural and Applied Sciences, Marian University College, P. O. Box 47, Bagamoyo, Tanzania.
⁴ Microbiology Section, Department of Biological Sciences, Faculty of Science, University of Botswana, Private Bag 00704, Gaborone, Botswana.
⁵ Department of Immunology and Molecular Biology, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda.
⁶ Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda.

Abstract

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 Escherichia coli (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 E. coli 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 in silico. The genome also harbors multidrug resistance genotypes including extended spectrum beta lactamase (ESBL) genes such as blaTEM-1A/B, sulfonamide resistance genes sul1/2, fluoroquinolone resistance genes dfrA5 and nonsynonymous mutations of the gene pmrB, 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.

Keywords: Escherichia coli ST58/24; ExPEC; Multidrug resistance; Sepsis; Sickle cell; Strain RSM044; Virulence.

Grants and funding

D43 TW010319/TW/FIC NIH HHS/United States