Expansion of a subset within C2 clade of Escherichia coli sequence type 131 (ST131) is driving the increasing rates of Aminoglycoside resistance: a molecular epidemiology report from Iran

Abstract

21The most important lineage of Escherichia coli, named sequence type 131 (ST131) is a 22 pandemic clone which drives the increasing rates of antibiotic resistance. While the 23 pervasiveness of ST131 clade C, especially subclades C2 and C1-M27 has been demonstrated in 24 numerous global surveys, no report about the ST131 clades and its virotypes has been published 25 from Iran, so far. So, in this study we investigated and compared the virotypes, antibiotic 26 susceptibility patterns, resistance/ virulence determinants and clonality of ST131 clades collected 27 during one-year surveillance study. 28 Most of isolates belonged to clade C2 (34/76 [44.7%]), with the highest virulence factor (VF) 29 scores and resistance rates. The distinctive profiles of clade C2 virulence genes were revealed by 30 "principle coordinates analysis" (PcoA) test. The distribution of hlyA/cnf1virulence genes among 31 clade C2 was not uniform, so that positive strains showed significantly higher rates of resistance 32 markers (bla CTX-M-15 , bla OXA-1 , aac6Ib/Ib-cr and aac3IIa) and ampicillin-33 sulbactam/gentamicin/tobramycin resistance. Virotype C as the most common virotype (48.7%) 34 was predominant among clade C1 population, while almost all of virotypes E and F [(22/23), 35 95.6%] strains belonged to clade C2, with the highest VF scores and aminoglycoside resistance 36 rates. "Multi locus variable Number tandem repeats analysis" (MLVA) clustered clades C1 and 37 C2 together, while clades A and B strains were mostly identified as singletons. 38 Appearance of virotypes E and F among clade C2 strains with higher rates of aminoglycoside 39 resistance/virulence genes content demonstrate the shifting dynamics of this pandemic clone in 40 response to antibiotic selection pressure by establishing the newly-emerged subsets. 41 (ST131), the currently emerged clone of Escherichia coli which is 60 disseminated worldwide cause severe hospital-acquired and community-onset infections (1, 2). 61The pervasiveness of ST131 has been reported by many global surveys and increasing 62 prevalence of fluoroquinolone and cephalosporine resistance in E. coli population is attributed to 63 this clone (3). 64Extensive studies of ST131 clone have been started from 10 years ago and it has found to be 65 rapidly expanding across the globe. The first description of this clone was in 2008 (4, 5) and has 66 now been found on every continent examined; it is estimated that up to 30% of all ExPEC 67 isolates in some regions belong to ST131 lineage (6). 68 69 whole genome sequencing analysis by several 70 studies revealed that ST131 consist of different clades: clade A, B and C (8). Generally, the 71 clades A and B which are minor parts of ST131 population, are susceptible to fluoroquinolone 72 and cephalosporine, while clade C (also known as H30) represents the largest clade and 73 comprises two sub-clades: C1 (or H30R) and C2 (H30Rx), both of which are resistant to 74 fluoroquinolone (8). The carriage of CTX-M-15 Extended Spectrum β-lactamase (ESBL) gene 75 wh...