Host Imprints on Bacterial Genomes—Rapid, Divergent Evolution in Individual Patients

Zdziarski, Jaroslaw; Brzuszkiewicz, Elżbieta; Wullt, Björn; Liesegang, Heiko; Biran, Dvora; Voigt, Birgit; Grönberg-Hernandez, Jenny; Ragnarsdóttir, Bryndís; Hecker, Michael; Ron, Eliora Z.; Daniel, Rolf; Gottschalk, Gerhard; Hacker, Jörg; Svanborg, Catharina; Dobrindt, Ulrich

doi:10.1371/journal.ppat.1001078

Cited by 128 publications

(133 citation statements)

References 53 publications

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“…Taken together, our data suggest E. coli VR50 is a commensal strain, remarkably similar to E. coli K-12, which has gained the ability to persist in the urinary tract through gene acquisition. This is in stark contrast to the prototypical ABU E. coli strain 83972, which appears to have evolved through mutation and gene loss from a virulent UPEC strain (9,10,(15)(16)(17)46).…”

Section: Phenotypic Characteristics Of E Coli Vr50 E Coli Vr50 (Ormentioning

confidence: 78%

“…Molecular and genomic analyses of the ABU prototype E. coli strain 83972 also support this observation. E. coli 83972 is a clinical isolate capable of long-term bladder colonization, as shown in human inoculation studies (13)(14)(15). The virulence-associated adhesin genes of E. coli 83972 have become attenuated through a series of independent mutational events.…”

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confidence: 99%

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Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

et al. 2015

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e Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder. U rinary tract infections (UTIs) are among the most common infectious diseases of humans and a major cause of morbidity. It is estimated that 40 to 50% of all adult women experience at least one UTI episode in their lifetime (1). In addition to welldocumented symptomatic infections, many UTIs are asymptomatic. These infections, referred to as asymptomatic bacteriuria (ABU), represent a carrier state that resembles commensalism and occur in a percentage of the population, depending on age and gender. ABU patients may carry Ͼ10 5 CFU of a single bacterial strain/ml of urine for months or years without significant symptoms.Escherichia coli causes more than 80% of all symptomatic and asymptomatic UTIs. In general, strains that cause symptomatic UTI are collectively described as uropathogenic E. coli (UPEC), while strains that cause asymptomatic UTI are referred to as ABU E. coli. Both UPEC and ABU E. coli strains exhibit a high degree of genetic diversity that is largely attributed to the presence of virulence/fitness genes on mobile genetic elements referred to as pathogenicity islands (PAIs) or genomic islands (GIs) (2, 3). While no single virulence factor is uniquely definitive for UPEC or ABU E. coli, the ability to colonize the urinary tract is enhanced by a number of factors, including fimbriae (e.g., type 1, P, F1C, and Afa), autotransporter proteins (e.g., Ag43, UpaB, and UpaH), cell surface polysaccharides (e.g., O antigen), and siderophores (e.g., ente...

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Section: Phenotypic Characteristics Of E Coli Vr50 E Coli Vr50 (Ormentioning

confidence: 78%

mentioning

confidence: 99%

Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

et al. 2015

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“…The prototype ABU or APN strains E. coli 83972 (OR:K5:H-) (13,(15)(16)(17) and E. coli CFT073 (O6:K2:H1) (59) were cultured on tryptic soy agar (16 hours, 37°C), harvested in PBS (pH 7.2, 10 10 CFU/ml), and diluted as appropriate. Human kidney carcinoma (A498, ATCC HTB44), human colon cancer (HT29, DLD-1, ATCC), and bladder carcinoma cells (J82, ATCC HTB-1 and ATCC HTB-9) were cultured in RPMI-1640 supplemented with 1 mM sodium pyruvate, 1 mM nonessential amino acids, gentamycin (50 μg/ml -1 ), and 5% FCS (PAA).…”

Section: Methodsmentioning

confidence: 99%

“…While virulent Escherichia coli cause severe, potentially life-threatening disease by breaking the inertia of the mucosal barrier and infecting the kidneys, the most common outcome of bacteriuria is an asymptomatic carrier state resembling commensalism at other mucosal sites (12). Patients with asymptomatic bacteriuria (ABU) may carry the same strain for months or years without developing a destructive host response, and the bacteria co-evolve with their hosts in a niche with little microbial competition (13). The molecular determinants of long-term bacterial persistence and adaptation are still poorly understood, however.…”

Section: Introductionmentioning

confidence: 99%

Bacterial control of host gene expression through RNA polymerase II

Lutay¹,

Ambite²,

Hernández³

et al. 2013

J. Clin. Invest.

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The normal flora furnishes the host with ecological barriers that prevent pathogen attack while maintaining tissue homeostasis. Urinary tract infections (UTIs) constitute a highly relevant model of microbial adaptation in which some patients infected with Escherichia coli develop acute pyelonephritis, while other patients with bacteriuria exhibit an asymptomatic carrier state similar to bacterial commensalism. It remains unclear if the lack of destructive inflammation merely reflects low virulence or if carrier strains actively inhibit disease-associated responses in the host. Here, we identify a new mechanism of bacterial adaptation through broad suppression of RNA polymerase II-dependent (Pol II-dependent) host gene expression. Over 60% of all genes were suppressed 24 hours after human inoculation with the prototype asymptomatic bacteriuria (ABU) strain E. coli 83972, and inhibition was verified by infection of human cells. Specific repressors and activators of Pol II-dependent transcription were modified, Pol II phosphorylation was inhibited, and pathogen-specific signaling was suppressed in cell lines and inoculated patients. An increased frequency of strains inhibiting Pol II was epidemiologically verified in ABU and fecal strains compared with acute pyelonephritis, and a Pol II antagonist suppressed the disease-associated host response. These results suggest that by manipulating host gene expression, ABU strains promote tissue integrity while inhibiting pathology. Such bacterial modulation of host gene expression may be essential to sustain asymptomatic bacterial carriage by ensuring that potentially destructive immune activation will not occur.

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“…Among these studies are anecdotal reports of protection against symptomatic P. aeruginosa UTIs, including 1 patient with asymptomatic cocolonization of 83972 and P. aeruginosa that progressed to UTI following loss of 83972 (26,66). E. coli 83972 possesses the Yersinia HPI (71,72) and was observed to produce escherichelin in ironrestricted medium (data not shown).…”

Section: Escherichelin Does Not Support Iron-dependent E Coli Growthmentioning

confidence: 99%

Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria

Ohlemacher¹,

Giblin²,

d’Avignon³

et al. 2017

Journal of Clinical Investigation

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Host Imprints on Bacterial Genomes—Rapid, Divergent Evolution in Individual Patients

Cited by 128 publications

References 53 publications

Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

Bacterial control of host gene expression through RNA polymerase II

Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria

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