Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection

Nisco, Nicole J. De; Neugent, Michael L.; Mull, Jason; Chen, Luming; Kuprasertkul, Amy; Santos, Marcela de Souza; Palmer, Kelli L.; Zimmern, Philippe E.; Orth, Kim

doi:10.1016/j.jmb.2019.04.008

Cited by 88 publications

(70 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…QIRs potentially provide inocula for reinfection after antibiotic treatment depletes extracellular bacteria in the bladder lumen. Consistent with the findings from this animal model, recent data from De Nisco and colleagues demonstrated the presence of bacteria in the bladder walls of women with RUTIs (12). From the bladder, the infection can spread to the kidneys (pyelonephritis) and the bloodstream (sepsis).…”

Section: Introductionsupporting

confidence: 81%

Rapid Growth and Metabolism of Uropathogenic Escherichia coli in Relation to Urine Composition

Reitzer

2019

Clin Microbiol Rev

Self Cite

View full text Add to dashboard Cite

SUMMARYUropathogenicEscherichia coli(UPEC) strains cause a majority of urinary tract infections (UTIs). Since UPEC strains can become antibiotic resistant, adjunct or alternate therapies are urgently needed. UPEC strains grow extremely rapidly in patients with UTIs. Thus, this review focuses on the relation between urine composition and UPEC growth and metabolism. Compilation of urinary components from two major data sources suggests the presence of sufficient amino acids and carbohydrates as energy sources and abundant phosphorus, sulfur, and nitrogen sources. In a mouse UTI model, mutants lacking enzymes of the tricarboxylic acid cycle, gluconeogenesis, and the nonoxidative branch of the pentose cycle are less competitive than the corresponding parental strains, which is consistent with amino acids as major energy sources. Other evidence suggests that carbohydrates are required energy sources. UPEC strains in urineex vivoandin vivoexpress transporters for peptides, amino acids, carbohydrates, and iron and genes associated with nitrogen limitation, amino acid synthesis, nucleotide synthesis, and nucleotide salvage. Mouse models confirm the requirement for many, but not all, of these genes. Laboratory evolution studies suggest that rapid nutrient uptake without metabolic rewiring is sufficient to account for rapid growth. Proteins and pathways required for rapid growth should be considered potential targets for alternate or adjunct therapies.

show abstract

Section: Introductionsupporting

confidence: 81%

Rapid Growth and Metabolism of Uropathogenic Escherichia coli in Relation to Urine Composition

Reitzer

2019

Clin Microbiol Rev

Self Cite

View full text Add to dashboard Cite

show abstract

“…Animal models demonstrated that bacteria can attach to the bladder surface, get internalized, and thus persist in the bladder wall where they remain protected from the action of antibiotics (5). Consistent with these findings, recent data from De Nisco and colleagues demonstrated the presence of bacteria in the bladder wall of women with rUTIs (6).…”

Section: Introductionsupporting

confidence: 64%

“…Except for W3110-LR, all other E. coli wild-type strains were obtained from Coli Genetic Stock Center at Yale University. Clinical isolates of uropathogenic E. coli were collected at University of Texas Southwestern Medical School from patients suffering from recurrent urinary tract infections (6). When constructing the mutant strains, an antibiotic resistance gene replaced the gene of interest.…”

Section: Methodsmentioning

confidence: 99%

FIMBRIAE AND FLAGELLA MEDIATED SURFACE MOTILITY AND THE EFFECT OF GLUCOSE ON NONPATHOGENIC AND UROPATHOGENICESCHERICHIA COLI

Ambagaspitiye¹,

Sudarshan²,

Hogins³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

word count: 223 15 Text word count (including abstract and importance): 3965 16 17 2ABSTRACT 18 We characterized the surface motility of nonpathogenic and pathogenic E. coli strains 19 with respect to the appendage requirement, flagella versus fimbriae, and the glucose requirement. 20 Nonpathogenic lab strains exhibited either slow or fast surface movement. The slow strains 21 required type 1 fimbriae for movement, while the fast strains required flagella and had an 22 insertion in the flhDC promoter region. Surface movement of three uropathogenic E. coli 23 (UPEC) strains was fast and required flagella, but these strains did not have an insertion in the 24 flhDC promoter region. We assessed swimming motility as an indicator of flagella synthesis and 25 found that glucose inhibited swimming of the slow nonpathogenic strains but not of the fast 26 nonpathogenic or pathogenic strains. Fimbriae-based surface motility requires glucose, which 27 inhibits cyclic-AMP (cAMP) and flagella synthesis; therefore, we examined whether surface 28 motility required cAMP. The surface motility of a slow, fimbriae-dominant, nonpathogenic strain 29 did not require cAMP, which was expected because fimbriae synthesis does not require cAMP. 30In contrast, the surface motility of a faster, flagella-dominant, UPEC strain required cAMP, 31 which was unexpected because swarming was unaffected by the presence of glucose. Electron 32 microscopy verified the presence or absence of fimbriae or flagella. In summary, surface 33 motilities of the nonpathogenic and uropathogenic E. coli strains of this study differed in the 34 appendage used and the effects of glucose on flagella synthesis. 35 36 IMPORTANCE 37Uropathogenic Escherichia coli strains cause 80-90% of community-acquired urinary 38 tract infections, and recurrent urinary tract infections, which can last for years, and often become 39 antibiotic resistant. Urinary tract infections can be associated with intra-vesical lesions extending 40 3 from localized trigonitis/cystitis to widely distributed pancystitis: motility may be a factor that 41 distinguishes between these infection patterns. Nonpathogenic and uropathogenic E. coli were 42 shown to exhibit fimbriae-and flagella-dependent surface motility, respectively, and the 43 difference was attributed to altered control of flagella synthesis by glucose. Uropathogenic E. 44 coli strains grow more rapidly in urine than nonpathogenic strains, which implies differences in 45 metabolism. Understanding the basis for glucose-insensitive control of flagella-dependent 46 motility could provide insight into uropathogenic E. coli metabolism and virulence. 47 48 49 Escherichia coli is an extraordinarily successful pathogen which causes a variety of 50 diseases, including urinary tract infections (1). Uropathogenic E. coli (UPEC) is the predominant 51 cause of acute and recurrent urinary tract infections, which can become antibiotic resistant and 52 persist for years (2, 3). In women with recurrent urinary tract infections (rUTIs), the cla...

show abstract

“…QIRs can persist for weeks to months, during which time the urine may be sterile; however, bacteria can reemerge from a QIR to cause a rUTI (25)(26)(27). Importantly, structures similar to IBCs can be found in the urine of human patients suffering from UTI, further supporting the relevance of experiments with the mouse model (28)(29)(30)(31).…”

mentioning

confidence: 86%

Adaptation of Arginine Synthesis among Uropathogenic Branches of the Escherichia coli Phylogeny Reveals Adjustment to the Urinary Tract Habitat

Hibbing

Dodson

Kalas

et al. 2020

mBio

View full text Add to dashboard Cite

Urinary tract infections (UTIs) are predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC pathogenesis requires passage through a severe population bottleneck involving intracellular bacterial communities (IBCs) that are clonal expansions of a single invading UPEC bacterium in a urothelial superficial facet cell. IBCs occur only during acute pathogenesis. The bacteria in IBCs form the founder population that develops into persistent extracellular infections. Only a small fraction of UPEC organisms proceed through the IBC cycle, regardless of the inoculum size. This dramatic reduction in population size precludes the utility of genomic mutagenesis technologies for identifying genes important for persistence. To circumvent this bottleneck, we previously identified 29 positively selected genes (PSGs) within UPEC and hypothesized that they contribute to virulence. Here, we show that 8 of these 29 PSGs are required for fitness during persistent bacteriuria. Conversely, 7/8 of these PSG mutants showed essentially no phenotype in acute UTI. Deletion of the PSG argI leads to arginine auxotrophy. Relative to the other arg genes, argI in the B2 clade (which comprises most UPEC strains) of E. coli has diverged from argI in other E. coli clades. Replacement of argI in a UPEC strain with a non-UPEC argI allele complemented the arginine auxotrophy but not the persistent bacteriuria defect, showing that the UPEC argI allele contributes to persistent infection. These results highlight the complex roles of metabolic pathways during infection and demonstrate that evolutionary approaches can identify infection-specific gene functions downstream of population bottlenecks, shedding light on virulence and the genetic evolution of pathogenesis. IMPORTANCE Uropathogenic Escherichia coli (UPEC) is the most common cause of human urinary tract infection (UTI). Population bottlenecks during early stages of UTI make high-throughput screens impractical for understanding clinically important later stages of UTI, such as persistence and recurrence. As UPEC is hypothesized to be adapted to these later pathogenic stages, we previously identified 29 genes evolving under positive selection in UPEC. Here, we found that 8 of these genes, including argI (which is involved in arginine biosynthesis), are important for persistence in a mouse model of UTI. Deletion of argI and other arginine synthesis genes resulted in (i) arginine auxotrophy and (ii) defects in persistent UTI. Replacement of a B2 clade argI with a non-B2 clade argI complemented arginine auxotrophy, but the resulting strain remained attenuated in its ability to cause persistent bacteriuria. Thus, argI may have a second function during UTI that is not related to simple arginine synthesis. This study demonstrates how variation in metabolic genes can impact virulence and provides insight into the mechanisms and evolution of bacterial virulence.

show abstract

Direct Detection of Tissue-Resident Bacteria and Chronic Inflammation in the Bladder Wall of Postmenopausal Women with Recurrent Urinary Tract Infection

Cited by 88 publications

References 46 publications

Rapid Growth and Metabolism of Uropathogenic Escherichia coli in Relation to Urine Composition

Rapid Growth and Metabolism of Uropathogenic Escherichia coli in Relation to Urine Composition

FIMBRIAE AND FLAGELLA MEDIATED SURFACE MOTILITY AND THE EFFECT OF GLUCOSE ON NONPATHOGENIC AND UROPATHOGENICESCHERICHIA COLI

Adaptation of Arginine Synthesis among Uropathogenic Branches of the Escherichia coli Phylogeny Reveals Adjustment to the Urinary Tract Habitat

Contact Info

Product

Resources

About