Croxall, G

McNally, A

Nottingham Trent Institutional Repository (IRep)

1 Pathogenesis of Escherichia coli from polymicrobial Urinary tract infections 2 3 Response to Piatti: 4 5 Gemma Croxall and Alan McNally 6 7 Pathogen Research Group, Nottingham Trent University, Clifton Lane, Nottingham 8 NG11 8NS 9 10 On behalf of the authors of our manuscript on pathogenesis of E. coli from 11 polymicrobial urinary tract infections (Croxall et al, 2011), we present a response to 12 the correspondence submitted by Gabriella Piatti. We thank the author for their 13 interest in our work, and especially welcome their comment on the importance of 14 studying such infections. We also hereby attempt to clarify some points of confusion 15 in the authors interpretation of the data displayed in the initial publication. 16 17 Piatti begins by stating that our analysis of antimicrobial resistance data was 18 (probably) performed regardless of patient group. We clearly state in our manuscript 19 that there was no difference in levels of antimicrobial resistance between 20 polymicrobial and monomicrobial samples. As there was no statistically significant 21 difference we chose not to present that data in detail given the amount of data we had 22 to present on what we considered our significant findings, namely that poylmicrobial 23 UTI contain high numbers of organisms with significant levels of antimicrobial 24 resistance and high levels of invasiveness and are going untreated in clinical settings. 25 The author is correct that this is not in agreement with previous literature, and that is a 26 key reason why we believe our study and others like it need to be conducted and 27 published. Only by performing controlled, co-ordinated equivalent studies across 28 multiple sites can a true evaluation of organisms circulating in polymicrobial UTI be 29 determined and compared. We believe this to be of immediate requirement in the field, 30 particularly when one considers comparisons of primary secondary and tertiary 31 healthcare facilities, as well as geographical variations in circulating bacterial 32 populations. 33 34 Piatti goes on to explain that the simultaneous discovery of enhanced ciprofoloxacin 35 resistance and increased pathogenic potential is in their opinion contradictory, and 36 that we have not compared "virulence genes" across our isolates. Additionally there is 37 a suggestion that without full analysis there is "doubt on the real significance of our 38 findings". Firstly, we do not consider enhanced resistance and pathogenesis within a 39 population of E. coli as contradictory at all. Particular attention has recently been paid 40 to the emergence of strains such as E. coli ST131 which is both highly resistant and 41 pathogenic. Additionally when viewing our results as a population it is clear there will 42 be some strains which have increased resistance and some which have increased 43 pathogenesis, and that the results cannot be generalised as all E. coli displaying both 44 phenotypes. The study of the population was outwith the scope of our manuscript, 45 which we state clearly in abstract, introduction and discussion is about highlighting 46 the presence of potentially dangerous pathogens in UTI samples that go untreated. 47 Similarly the presence of "virulence genes" would need to have been conducted at the 48 level of our E. coli population, outwith the scope of our manuscript. The author will 49 be pleased to know that a comprehensive analysis of the E. coli population was 50 conducted, and is currently under review for publication in another journal. In that 1 51 work the entire population is genotyped by M L S T and the V A G multiplex P C R they 52 refer to (Johnson & Stell, 2000) and correlated to antimicrobial resistance on a strain 53 by strain basis. The debate of "virulence genes" is a contentious one also, particularly 54 in E x P E C where it would appear there is no real virulence gene signature to speak of, 55 rather that E. coli has a vast array of tools to choose from the accessory gene pool 56 within which there is enormous overlap and redundancy (Barl et al, 2008, 57 Bielaszewska et al., 2007, Brzuszkiewicz et al., 2006, Dobrindt et al., 2004). 58 59 One final point from Piatti is that when studying ciprofloxacin resistance we did so 60 only in elderly patients and did not analyse catheterised - v - non-catheterised patients. 61 W e state in the manuscript a comparison between those 2 groups showing no 62 significant difference. Indeed most of our comparative analyses across those 2 groups 63 were not significant, primarily due to the sampling bias given to allow collection of 64 primarily polymicrobial samples, and therefore far fewer catheterised patients. The 65 reason this was done is the same as the reason we studied elderly patients, namely that 66 the funding generously received from the Dowager Countess Eleanor Peel trust was to 67 study the potential pathogens present in, and going untreated in, polymicrobial U T I in 68 elderly patients, as made clear throughout the presentation of our work. Undoubtedly 69 our findings have opened up the possibility of similar studies across wider cohorts, 70 and we encourage Piatti and others to join us in studying this topic to a much greater 71 level. 72 73 References: 74 Barl, T. , Dobrindt, U. , Y u , X. , Katcoff, D. J . , Sompolinsky, D., Bonacorsi, S., 75 Hacker, J . & Bachmanna, T. T. (2008). Genotyping D N A chip for the simultaneous 76 assessment of antibiotic resistance and pathogenic potential of extraintestinal 77 pathogenic Escherichia coli. Int. J. Antimicrob. Agents 32, 272-277'. 78 Bielaszewska, M . , Dobrindt, U. , Gartner, J . , Gallitz, L , Hacker, J . , Karch, H . , 79 Muller, D., Schuberte, S., Schmidt, M . A. & other authors (2007). Aspects of 80 genome plasticity in pathogenic Escherichia coli. Internal J. Med. Microbiol. 297, 81 625-639. 82 Brzuszkiewicz, E . , Bruggemann, H . , Liesegang, H . , Emmerth, M . , Olschlager, T., 83 Nagy, G. , Albermann, K. , Wagner, C , Buchrieser, C . & other authors (2006). 84 H o w to become a uropathogen: comparative genomic analysis of extraintestinal 85 pathogenic Escherichia coli strains. Proc Nat Acad Sci USA. 103, 12879-84. 86 Croxall, G . , Weston, V. , Joseph, S., Manning, G. , Cheetham, P. & McNally, A . 87 (2011). Increased Human Pathogenic Potential of Escherichia coli from 88 Polymicrobial Urinary Tract Infections in Comparison to Isolates from 89 Monomicrobial Culture Samples. J. Med Microbiol. 60, 102-102-109. 90 Dobrindt, U. , Hochhut, B., Hentschel, U. & Hacker, J . (2004). Genomic islands in 91 pathogenic and environmental microorganisms. Nat Rev Microbiol 2, 414-424. 92 Johnson, J . R. & Stell, A. L . (2000). Extended virulence genotypes of Escherichia 93 coli strains from patients with urosepsis in relation to phylogeny and host compromise. 94 J. Infect. Dis. 181, 261-272. 2 

Author's reply to 'Pathogenesis of Escherichia coli from polymicrobial urinary tract infections'

http://irep.ntu.ac.uk/id/eprint/13192/1/205593_7749%20McNally%20Postprint.pdf

Author's reply to 'Pathogenesis of Escherichia coli from polymicrobial urinary tract infections'

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