TY - JOUR
T1 - Molecularly defined extraintestinal pathogenic Escherichia coli status predicts virulence in a murine sepsis model better than does virotype, individual virulence genes, or clonal subset among E. coli ST131 isolates
AU - Merino, Irene
AU - Porter, Stephen B.
AU - Johnston, Brian
AU - Clabots, Connie
AU - Thuras, Paul
AU - Ruiz-Garbajosa, Patricia
AU - Cantón, Rafael
AU - Johnson, James R.
N1 - Publisher Copyright:
©, This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Background: Escherichia coli ST131, mainly its H30 clade, is the leading cause of extraintestinal E. coli infections but its correlates of virulence are undefined. Materials and methods: We tested in a murine sepsis model 84 ST131 isolates that differed by country of origin (Spain vs. USA), clonal subset, resistance markers, and virulence genes (VGs). Virulence outcomes, including illness severity score (ISS) and “killer” status (>80% mouse lethality), were compared statistically with clonal subset, individual and combined VGs, molecularly defined extraintestinal and uropathogenic E. coli (ExPEC, UPEC) status, and country of origin. Results: Virulence varied widely by strain. Univariable correlates of median ISS and percent “killer” (outcomes if variable present vs. absent) included pap (ISS, 4.4 vs. 3.8; “killer”, 71% vs. 46%), kpsMII (4.1 vs. 2.3; 59% vs. 25%), K2/K100 (4.4 vs. 3.2; 77% vs. 41%), ExPEC (4.2 vs. 2.2; 62% vs. 17%), Spanish origin (4.3 vs. 3.1; 65% vs. 36%), and H30R1 subset (2.5 vs. 4.1; 35% vs. 59%). With multivariable adjustment, ExPEC status was the only consistently significantly predictive variable. Conclusion: Within ST131 the strongest predictor of experimental virulence was molecularly defined ExPEC status. Clonal subsets seemed to behave differently in the murine sepsis model by country of origin.
AB - Background: Escherichia coli ST131, mainly its H30 clade, is the leading cause of extraintestinal E. coli infections but its correlates of virulence are undefined. Materials and methods: We tested in a murine sepsis model 84 ST131 isolates that differed by country of origin (Spain vs. USA), clonal subset, resistance markers, and virulence genes (VGs). Virulence outcomes, including illness severity score (ISS) and “killer” status (>80% mouse lethality), were compared statistically with clonal subset, individual and combined VGs, molecularly defined extraintestinal and uropathogenic E. coli (ExPEC, UPEC) status, and country of origin. Results: Virulence varied widely by strain. Univariable correlates of median ISS and percent “killer” (outcomes if variable present vs. absent) included pap (ISS, 4.4 vs. 3.8; “killer”, 71% vs. 46%), kpsMII (4.1 vs. 2.3; 59% vs. 25%), K2/K100 (4.4 vs. 3.2; 77% vs. 41%), ExPEC (4.2 vs. 2.2; 62% vs. 17%), Spanish origin (4.3 vs. 3.1; 65% vs. 36%), and H30R1 subset (2.5 vs. 4.1; 35% vs. 59%). With multivariable adjustment, ExPEC status was the only consistently significantly predictive variable. Conclusion: Within ST131 the strongest predictor of experimental virulence was molecularly defined ExPEC status. Clonal subsets seemed to behave differently in the murine sepsis model by country of origin.
KW - E. coli
KW - ExPEC
KW - mouse sepsis model
KW - virulence
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U2 - 10.1080/21505594.2020.1747799
DO - 10.1080/21505594.2020.1747799
M3 - Article
C2 - 32264739
AN - SCOPUS:85083208527
SN - 2150-5594
VL - 11
SP - 327
EP - 336
JO - Virulence
JF - Virulence
IS - 1
ER -