Success of Escherichia coli O25b:H4 ST131 clade C associated with a decrease in virulence

Abstract

word count: 248 22 Text word count: 5256 23 24 25 2 Abstract 26 Escherichia coli of sequence type (ST) 131 resistant to fluoroquinolones and producer of 27CTX-M-15 is globally one of the major extraintestinal pathogenic E. coli (ExPEC). ST131 28 phylogenesis showed that multidrug-resistant ST131 strains belong to a clade called C, 29 descending from an ancestral clade called B, comprising mostly antibiotic-susceptible strains. 30 Antibiotic resistance could appear as one of the keys of the clade C global success. We 31 hypothesized that other features of ST131 clade C could contribute to this success since other 32 major global ExPEC clones (ST73, ST95) are mostly antibiotic-susceptible. To test this 33 hypothesis, we measured the growth abilities, early biofilm formation and virulence-factor 34 content of a collection of clade B and clade C strains. Moreover, using competition assays, we 35 measured the capacity of selected representative strains of clades B and C to colonize the 36 mouse intestine and urinary tract, and to kill mice in a septicemia model. Clade B and C 37 strains had similar growth ability. However, clade B strains were more frequently early 38 biofilm producers, expressed mostly faster their type 1 fimbriae and displayed more virulence 39 factor-encoding genes than clade C strains. Clade B outcompeted clade C in the gut and/or 40 urinary tract colonization models and in the septicemia model. These results strongly suggest 41 that clade C strain evolution includes a loss of virulence, i.e. a process that could enhance 42 micro-organism persistence in a given host and thus optimize transmission. This process, 43 associated with acquired antibiotic-resistance, could ensure clade C strain survival in 44 environments under antibiotic pressure.45 46 47 48 49 50 3 Importance 51Extraintestinal pathogen Escherichia coli (ExPEC) are virulent but mostly antibiotic-52 susceptible. One worrying exception is ST131, a major multidrug resistant ExPEC clone that 53 has spread worldwide since the 2000s. To contain the emergence of this threatening clone, we 54 need to understand what factors favored its emergence and dissemination. Here, we 55 investigated whether multidrug-resistant ST131 had advantageous phenotypic properties 56 beyond multidrug resistance. To this end, we competed the emergent multidrug-resistant 57 ST131 with its antibiotic-susceptible ancestor in different conditions: biofilm production, in 58 vivo colonization and virulence experiments. In all in vivo competitions, we found that 59 multidrug-resistant ST131 was losing to its ancestor, suggesting a lesser virulence of 60 multidrug-resistant ST131. It was previously described that losing virulence can increase 61 micro-organism persistence in some populations and subsequently its level of transmissibility. 62Thus, a decreased level of virulence, associated with multidrug resistance, could explain the 63 global success of ST131. 64 65 66 67 68 69 70 71 72 73 74 75 In the last two decades, Escherichia coli O25b:H4 of sequence type (ST) ...

Plasmids shape the diverse accessory resistomes of Escherichia coli ST131

“…Although 83 972 lost virulence during its adaptation to commensalism [122], here it had AMR genes like PBP3 that it shared with an E. coli gut microbiome (3_2_53FAA). This retention of certain AMR genes in asymptomatic specimens is important when assessing the AMR gene evolution in ST131 [123,124].…”

“…coli gut microbiome (3_2_53FAA). This retention of certain AMR genes in asymptomatic specimens is important when assessing the AMR gene evolution in ST131 [123, 124].…”

Plasmids shape the diverse accessory resistomes ofEscherichia coliST131

“…Although 83972 lost virulence during its adaptation to commensalism [123], here it had AMR genes like PBP3 that it shared with an E. coli gut microbiome (3_2_53FAA). This retention of certain AMR genes in asymptomatic specimens is important when assessing the AMR gene evolution in ST131 [124][125]. Within ST131, Clade C core genomes are highly conserved but accessory genomes have extensive differences in AMR gene content [50,52,61].…”