Multiresistant Uropathogenic Escherichia coli from a Region in India Where Urinary Tract Infections Are Endemic: Genotypic and Phenotypic Characteristics of Sequence Type 131 Isolates of the CTX-M-15 Extended-Spectrum-β-Lactamase-Producing Lineage

ABSTRACTEscherichia colisequence type 131 (O25b:H4), associated with the CTX-M-15 extended-spectrum beta-lactamases (ESBLs) and linked predominantly to the community-onset antimicrobial-resistant infections, has globally emerged as a public health concern. However, scant attention is given to the understanding of the molecular epidemiology of these strains in high-burden countries such as India. Of the 100 clinicalE. coliisolates obtained by us from a setting where urinary tract infections are endemic, 16 ST131E. coliisolates were identified by multilocus sequence typing (MLST). Further, genotyping and phenotyping methods were employed to characterize their virulence and drug resistance patterns. All the 16 ST131 isolates harbored the CTX-M-15 gene, and half of them also carried TEM-1; 11 of these were positive forblaOXAgroups 1 and 12 foraac(6′)-Ib-cr. At least 12 isolates were refractory to four non-beta-lactam antibiotics: ciprofloxacin, gentamicin, sulfamethoxazole-trimethoprim, and tetracycline. Nine isolates carried the class 1 integron. Plasmid analysis indicated a large pool of up to six plasmids per strain with a mean of approximately three plasmids. Conjugation and PCR-based replicon typing (PBRT) revealed that the spread of resistance was associated with the FIA incompatibility group of plasmids. Pulsed-field gel electrophoresis (PFGE) and genotyping of the virulence genes showed a low level of diversity among these strains. The association of ESBL-encoding plasmid with virulence was demonstrated in transconjugants by serum assay. None of the 16 ST131 ESBL-producingE. colistrains were known to synthesize carbapenemase enzymes. In conclusion, our study reports a snapshot of the highly virulent/multiresistant clone ST131 of uropathogenicE. colifrom India. This study suggests that the ST131 genotypes from this region are clonally evolved and are strongly associated with the CTX-M-15 enzyme, carry a high antibiotic resistance background, and have emerged as an important cause of community-acquired urinary tract infections.

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Relative Fecal Abundance of Extended-Spectrum-β-Lactamase-Producing Escherichia coli Strains and Their Occurrence in Urinary Tract Infections in Women

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00238-13 ◽

2013 ◽

Vol 57 (9) ◽

pp. 4512-4517 ◽

Cited By ~ 58

Author(s):

Etienne Ruppé ◽

Brandusa Lixandru ◽

Radu Cojocaru ◽

Çağrı Büke ◽

Elisabeth Paramythiotou ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Virulence Factors ◽

Urinary Tract Infections ◽

Predictive Values ◽

Content Type ◽

Extended Spectrum Beta Lactamase ◽

E Coli ◽

Extended Spectrum ◽

Tract Infections

ABSTRACTExtended-spectrum-beta-lactamase (ESBL)-producingEscherichia coli(ESBLE. coli) strains are of major concern because few antibiotics remain active against these bacteria. We investigated the association between the fecal relative abundance (RA) of ESBL-producingE. coli(ESBL-RA) and the occurrence of ESBLE. coliurinary tract infections (UTIs). The first stool samples passed after suspicion of UTI from 310 women with subsequently confirmedE. coliUTIs were sampled and tested for ESBL-RA by culture on selective agar. Predictive values of ESBL-RA for ESBLE. coliUTI were analyzed for women who were not exposed to antibiotics when the stool was passed. ESBLE. coliisolates were characterized for ESBL type, phylogroup, relatedness, and virulence factors. The prevalence of ESBLE. colifecal carriage was 20.3%, with ESBLE. coliUTIs being present in 12.3% of the women. The mean ESBL-RA (95% confidence interval [CI]) was 13-fold higher in women exposed to antibiotics at the time of sampling than in those not exposed (14.3% [range, 5.6% to 36.9%] versus 1.1% [range, 0.32% to 3.6%], respectively;P< 0.001) and 18-fold higher in women with ESBLE. coliUTI than in those with anotherE. coliUTI (10.0% [range, 0.54% to 100%] versus 0.56% [range, 0.15% to 2.1%[, respectively;P< 0.05). An ESBL-RA of <0.1% was 100% predictive of a non-ESBLE. coliUTI. ESBL type, phylogroup, relatedness, and virulence factors were not found to be associated with ESBL-RA. In conclusion, ESBL-RA was linked to the occurrence of ESBLE. coliUTI in women who were not exposed to antibiotics and who had the same clone ofE. coliin urine samples and fecal samples. Especially, a low ESBL-RA appeared to be associated with a low risk of ESBLE. coliinfection.

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Escherichia coli from community-acquired urinary tract infections resistant to fluoroquinolones and extended-spectrum beta-lactams

The Journal of Infection in Developing Countries ◽

10.3855/jidc.361 ◽

2007 ◽

Vol 1 (03) ◽

pp. 257-262 ◽

Cited By ~ 25

Author(s):

Samuel Kariuki ◽

Gunturu Revathi ◽

John Corkill ◽

John Kiiru ◽

Joyce Mwituria ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Nalidixic Acid ◽

Urinary Tract Infections ◽

Acid Resistance ◽

Beta Lactam ◽

E Coli ◽

Extended Spectrum ◽

Tract Infections ◽

Multiple Drugs

Background: Uropathogenic Escherichia coli are increasingly becoming resistant to flouroquinolones and to other commonly available antimicrobials. We sought to investigate the genetic basis for fluoroquinolone and extended spectrum beta-lactam (ESBL) resistance in 17 fluoroquinolone-resistant (MIC of levofloxacin and ciprofloxacin >32 μg/ml) E. coli isolated from patients with urinary tract infections (UTIs). Methods: We applied PCR and Pulsed Field Gel Electrophoresis (PFGE) to characterize resistance genes and to determine clonal relatedness of strains, respectively. Results: Twelve of the 17 E. coli were resistant to multiple drugs, including ampicillin, co-amoxyclav, cefotaxime, ceftriaxone, ceftazidime and gentamicin and nalidixic acid and produced plasmid-mediated CTX-M-15 type ESBLs and CMY-2 AmpC type enzymes. The other 5 E. coli that were non-ESBL-producing were multiply resistant to ampicillin, nitrofurantoin, cefoxitin, nalidixic acid. Resistance to fluoroquinolones resulted from a combination of the presence of qnrA, qnrB, ciprofloxacin acetylating enzyme designated aac(6’)-1b-cr, and mutations in the two amino acid substitutions; 83 Serine (TCG) to Leucine (TTG) and 87 Aspartic acid (GAC) to Asparagine (AAC). Conclusion: Antibiogram patterns and PFGE of E. coli showed that these were community acquired UTI caused by pockets of clonally-related and some discreet strain types. Plasmid-mediated CTX-M-15 beta-lactamases and CMY-2 AmpC enzymes and fluoroquinolone resistant E. coli are becoming increasingly prevalent in hospitals in Kenya, posing a major challenge in the management of UTIs.

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Single Clinical Isolates from Acute Uncomplicated Urinary Tract Infections Are Representative of Dominant In Situ Populations

mBio ◽

10.1128/mbio.01064-13 ◽

2014 ◽

Vol 5 (2) ◽

Cited By ~ 18

Author(s):

Dana Willner ◽

Serene Low ◽

Jason A. Steen ◽

Narelle George ◽

Graeme R. Nimmo ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Clinical Isolates ◽

Content Type ◽

E Coli ◽

Strain Diversity ◽

Amplicon Pyrosequencing ◽

Culture Independent ◽

Tract Infections

ABSTRACTUrinary tract infections (UTIs) are one of the most commonly acquired bacterial infections in humans, and uropathogenicEscherichia colistrains are responsible for over 80% of all cases. The standard method for identification of uropathogens in clinical laboratories is cultivation, primarily using solid growth media under aerobic conditions, coupled with morphological and biochemical tests of typically a single isolate colony. However, these methods detect only culturable microorganisms, and characterization is phenotypic in nature. Here, we explored the genotypic identity of communities in acute uncomplicated UTIs from 50 individuals by using culture-independent amplicon pyrosequencing and whole-genome and metagenomic shotgun sequencing. Genus-level characterization of the UTI communities was achieved using the 16S rRNA gene (V8 region). Overall UTI community richness was very low in comparison to other human microbiomes. We strain-typedEscherichia-dominated UTIs using amplicon pyrosequencing of the fimbrial adhesin gene,fimH. There were nine highly abundantfimHtypes, and each UTI sample was dominated by a single type. Molecular analysis of the corresponding clinical isolates revealed that in the majority of cases the isolate was representative of the dominant taxon in the community at both the genus and the strain level. Shotgun sequencing was performed on a subset of eightE. coliurine UTI and isolate pairs. The majority of UTI microbial metagenomic sequences mapped to isolate genomes, confirming the results obtained using phylogenetic markers. We conclude that for the majority of acute uncomplicatedE. coli-mediated UTIs, single cultured isolates are diagnostic of the infection.IMPORTANCEIn clinical practice, the diagnosis and treatment of acute uncomplicated urinary tract infection (UTI) are based on analysis of a single bacterial isolate cultured from urine, and it is assumed that this isolate represents the dominant UTI pathogen. However, these methods detect only culturable bacteria, and the existence of multiple pathogens as well as strain diversity within a single infection is not examined. Here, we explored bacteria present in acute uncomplicated UTIs using culture-independent sequence-based methods.Escherichia coliwas the most common organism identified, and analysis ofE. colidominant UTI samples and their paired clinical isolates revealed that in the majority of infections the cultured isolate was representative of the dominant taxon at both the genus and the strain level. Our data demonstrate that in most cases single cultured isolates are diagnostic of UTI and are consistent with the notion of bottlenecks that limit strain diversity during UTI pathogenesis.

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Role of Urinary Cathelicidin LL-37 and Human β-Defensin 1 in Uncomplicated Escherichia coli Urinary Tract Infections

Infection and Immunity ◽

10.1128/iai.01393-13 ◽

2014 ◽

Vol 82 (4) ◽

pp. 1572-1578 ◽

Cited By ~ 41

Author(s):

Karen L. Nielsen ◽

Pia Dynesen ◽

Preben Larsen ◽

Lotte Jakobsen ◽

Paal S. Andersen ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Adult Women ◽

Content Type ◽

E Coli ◽

Innate Defense ◽

High Level ◽

Tract Infections

ABSTRACTCathelicidin (LL-37) and human β-defensin 1 (hBD-1) are important components of the innate defense in the urinary tract. The aim of this study was to characterize whether these peptides are important for developing uncomplicatedEscherichia coliurinary tract infections (UTIs). This was investigated by comparing urinary peptide levels of UTI patients during and after infection to those of controls, as well as characterizing the fecal flora of participants with respect to susceptibility to LL-37 andin vivovirulence. Forty-seven UTI patients and 50 controls who had never had a UTI were included. Participants were otherwise healthy, premenopausal, adult women. LL-37 MIC levels were compared for fecalE. coliclones from patients and controls and were also compared based on phylotypes (A, B1, B2, and D).In vivovirulence was investigated in the murine UTI model by use of selected fecal isolates from patients and controls. On average, UTI patients had significantly more LL-37 in urine during infection than postinfection, and patient LL-37 levels postinfection were significantly lower than those of controls. hBD-1 showed similar urine levels for UTI patients and controls. FecalE. coliisolates from controls had higher LL-37 susceptibility than fecal and UTIE. coliisolates from UTI patients.In vivostudies showed a high level of virulence of fecalE. coliisolates from both patients and controls and showed no difference in virulence correlated with the LL-37 MIC level. The results indicate that the concentration of LL-37 in the urinary tract and low susceptibility to LL-37 may increase the likelihood of UTI in a complex interplay between host and pathogen attributes.

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Outbreak of extended spectrum beta-lactamase producing E. coli in a nursing home in Ireland, May 2006

Weekly releases (1997–2007) ◽

10.2807/esw.11.35.03036-en ◽

2006 ◽

Vol 11 (35) ◽

Cited By ~ 1

Author(s):

H Pelly ◽

D Morris ◽

E O’Connell ◽

B Hanahoe ◽

C Chambers ◽

...

Keyword(s):

Escherichia Coli ◽

Nursing Home ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Beta Lactamase ◽

Extended Spectrum Beta Lactamase ◽

E Coli ◽

Extended Spectrum ◽

Tract Infections

In May 2006, a consultant microbiologist noted two isolates of extended spectrum beta-lactamase (ESBL)-producing Escherichia coli associated with urinary tract infections in a single week in two residents in a nursing home in Ireland

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Diversity and Population Overlap between Avian and HumanEscherichia coliBelonging to Sequence Type 95

mSphere ◽

10.1128/msphere.00333-18 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 11

Author(s):

Steffen L. Jørgensen ◽

Marc Stegger ◽

Eglé Kudirkiene ◽

Berit Lilje ◽

Louise L. Poulsen ◽

...

Keyword(s):

Urinary Tract ◽

Urinary Tract Infections ◽

Large Scale ◽

Sequence Type ◽

Comparative Genomic ◽

Avian Host ◽

Whole Genome ◽

Content Type ◽

E Coli ◽

Tract Infections

ABSTRACTAvian-pathogenicEscherichia coli(APEC) is a subgroup of extraintestinal pathogenicE.coli(ExPEC) presumed to be zoonotic and to represent an external reservoir for extraintestinal infections in humans, including uropathogenicE. coli(UPEC) causing urinary tract infections. Comparative genomics has previously been applied to investigate whether APEC and human ExPEC are distinct entities. Even so, whole-genome-based studies are limited, and large-scale comparisons focused on single sequence types (STs) are not available yet. In this study, comparative genomic analysis was performed on 323 APEC and human ExPEC genomes belonging to sequence type 95 (ST95) to investigate whether APEC and human ExPEC are distinct entities. Our study showed that APEC of ST95 did not constitute a unique ExPEC branch and was genetically diverse. A large genetic overlap between APEC and certain human ExPEC was observed, with APEC located on multiple branches together with closely related human ExPEC, including nearly identical APEC and human ExPEC. These results illustrate that certain ExPEC clones may indeed have the potential to cause infection in both poultry and humans. Previously described ExPEC-associated genes were found to be encoded on ColV plasmids. These virulence-associated plasmids seem to be crucial for ExPEC strains to cause avian colibacillosis and are strongly associated with strains of the mixed APEC/human ExPEC clusters. The phylogenetic analysis revealed two distinct branches consisting of exclusively closely related human ExPEC which did not carry the virulence-associated plasmids, emphasizing a lower avian virulence potential of human ExPEC in relation to an avian host.IMPORTANCEAPEC causes a range of infections in poultry, collectively called colibacillosis, and is the leading cause of mortality and is associated with major economic significance in the poultry industry. A growing number of studies have suggested APEC as an external reservoir of human ExPEC, including UPEC, which is a reservoir. ExPEC belonging to ST95 is considered one of the most important pathogens in both poultry and humans. This study is the first in-depth whole-genome-based comparison of ST95E. coliwhich investigates both the core genomes as well as the accessory genomes of avian and human ExPEC. We demonstrated that multiple lineages of ExPEC belonging to ST95 exist, of which the majority may cause infection in humans, while only part of the ST95 cluster seem to be avian pathogenic. These findings further support the idea that urinary tract infections may be a zoonotic infection.

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Escherichia coli CFT073 Fitness Factors during Urinary Tract Infection: Identification Using an Ordered Transposon Library

Applied and Environmental Microbiology ◽

10.1128/aem.00691-20 ◽

2020 ◽

Vol 86 (13) ◽

Cited By ~ 1

Author(s):

Allyson E. Shea ◽

Juan Marzoa ◽

Stephanie D. Himpsl ◽

Sara N. Smith ◽

Lili Zhao ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Human Urine ◽

Transposon Mutagenesis ◽

Content Type ◽

E Coli ◽

Tract Infections

ABSTRACT Urinary tract infections (UTI), the second most diagnosed infectious disease worldwide, are caused primarily by uropathogenic Escherichia coli (UPEC), placing a significant financial burden on the health care system. High-throughput transposon mutagenesis combined with genome-targeted sequencing is a powerful technique to interrogate genomes for fitness genes. Genome-wide analysis of E. coli requires random libraries of at least 50,000 mutants to achieve 99.99% saturation; however, the traditional murine model of ascending UTI does not permit testing of large mutant pools due to a bottleneck during infection. To address this, an E. coli CFT073 transposon mutant ordered library of 9,216 mutants was created and insertion sites were identified. A single transposon mutant was selected for each gene to assemble a condensed library consisting of 2,913 unique nonessential mutants. Using a modified UTI model in BALB/c mice, we identified 36 genes important for colonizing the bladder, including purB, yihE, and carB. Screening of the condensed library in vitro identified yigP and ubiG to be essential for growth in human urine. Additionally, we developed a novel quantitative PCR (qPCR) technique to identify genes with fitness defects within defined subgroups of related genes (e.g., genes encoding fimbriae, toxins, etc.) following UTI. The number of mutants within these subgroups circumvents bottleneck restriction and facilitates validation of multiple mutants to generate individual competitive indices. Collectively, this study investigates the bottleneck effects during UTI, provides two techniques for evading those effects that can be applied to other disease models, and contributes a genetic tool in prototype strain CFT073 to the field. IMPORTANCE Uropathogenic Escherichia coli strains cause most uncomplicated urinary tract infections (UTI), one of the most common infectious diseases worldwide. Random transposon mutagenesis techniques have been utilized to identify essential bacterial genes during infection; however, this has been met with limitations when applied to the murine UTI model. Conventional high-throughput transposon mutagenesis screens are not feasible because of inoculum size restrictions due to a bottleneck during infection. Our study utilizes a condensed ordered transposon library, limiting the number of mutants while maintaining the largest possible genome coverage. Screening of this library in vivo, and in human urine in vitro, identified numerous candidate fitness factors. Additionally, we have developed a novel technique using qPCR to quantify bacterial outputs following infection with small subgroups of transposon mutants. Molecular approaches developed in this study will serve as useful tools to probe in vivo models that are restricted by anatomical, physiological, or genetic bottleneck limitations.

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Pharmacodynamic Evaluation of Fosfomycin against Escherichia coli and Klebsiella spp. from Urinary Tract Infections and the Influence of pH on Fosfomycin Activities

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02498-16 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 12

Author(s):

Nayara Helisandra Fedrigo ◽

Josmar Mazucheli ◽

James Albiero ◽

Danielle Rosani Shinohara ◽

Fernanda Gomes Lodi ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Oral Dose ◽

Single Oral Dose ◽

Urinary Tract Infections ◽

Bacterial Isolates ◽

Gram Negative ◽

Content Type ◽

E Coli ◽

Tract Infections

ABSTRACT Fosfomycin is widely used for the treatment of uncomplicated urinary tract infection (UTI), and it has recently been recommended that fosfomycin be used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacilli. Whether urine acidification can improve bacterial susceptibility to fosfomycin oral dosing regimens has not been analyzed. The MIC of fosfomycin for 245 Gram-negative bacterial isolates, consisting of 158 Escherichia coli isolates and 87 Klebsiella isolates which were collected from patients with urinary tract infections, were determined at pH 6.0 and 7.0 using the agar dilution method. Monte Carlo simulation of the urinary fosfomycin area under the concentration-time curve (AUC) after a single oral dose of 3,000 mg fosfomycin and the MIC distribution were used to determine the probability of target attainment (PTA). Fosfomycin was effective against E. coli (MIC90 ≤ 16 μg/ml) but not against Klebsiella spp. (MIC90 > 512 μg/ml). Acidification of the environment increased the susceptibility of 71% of the bacterial isolates and resulted in a statistically significant decrease in bacterial survival. The use of a regimen consisting of a single oral dose of fosfomycin against an E. coli isolate with an MIC of ≤64 mg/liter was able to achieve a PTA of ≥90% for a target pharmacodynamic index (AUC/MIC) of 23 in urine; PTA was not achieved when the MIC was higher than 64 mg/liter. The cumulative fractions of the bacterial responses (CFR) were 99% and 55% against E. coli and Klebsiella spp., respectively, based on simulated drug exposure in urine with an acidic pH of 6.0. A decrease of the pH from 7.0 to 6.0 improved the PTA and CFR of the target pharmacodynamic index in both E. coli and Klebsiella isolates.

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In Vitro Efficacy of Flomoxef against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Associated with Urinary Tract Infections in Malaysia

Antibiotics ◽

10.3390/antibiotics10020181 ◽

2021 ◽

Vol 10 (2) ◽

pp. 181

Author(s):

Soo Tein Ngoi ◽

Cindy Shuan Ju Teh ◽

Chun Wie Chong ◽

Kartini Abdul Jabar ◽

Shiang Chiet Tan ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Klebsiella Pneumoniae ◽

Urinary Tract Infections ◽

In Vitro Susceptibility ◽

E Coli ◽

Extended Spectrum ◽

Tract Infections ◽

Esbl Producers

The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has greatly affected the clinical efficacy of β-lactam antibiotics in the management of urinary tract infections (UTIs). The limited treatment options have resulted in the increased use of carbapenem. However, flomoxef could be a potential carbapenem-sparing strategy for UTIs caused by ESBL-producers. Here, we compared the in vitro susceptibility of UTI-associated ESBL-producers to flomoxef and established β-lactam antibiotics. Fifty Escherichia coli and Klebsiella pneumoniae strains isolated from urine samples were subjected to broth microdilution assay, and the presence of ESBL genes was detected by polymerase chain reactions. High rates of resistance to amoxicillin-clavulanate (76–80%), ticarcillin-clavulanate (58–76%), and piperacillin-tazobactam (48–50%) were observed, indicated by high minimum inhibitory concentration (MIC) values (32 µg/mL to 128 µg/mL) for both species. The ESBL genes blaCTX-M and blaTEM were detected in both E. coli (58% and 54%, respectively) and K. pneumoniae (88% and 74%, respectively), whereas blaSHV was found only in K. pneumoniae (94%). Carbapenems remained as the most effective antibiotics against ESBL-producing E. coli and K. pneumoniae associated with UTIs, followed by flomoxef and cephamycins. In conclusion, flomoxef may be a potential alternative to carbapenem for UTIs caused by ESBL-producers in Malaysia.

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Dissemination and Systemic Colonization of Uropathogenic Escherichia coli in a Murine Model of Bacteremia

mBio ◽

10.1128/mbio.00262-10 ◽

2010 ◽

Vol 1 (5) ◽

Cited By ~ 46

Author(s):

Sara N. Smith ◽

Erin C. Hagan ◽

M. Chelsea Lane ◽

Harry L. T. Mobley

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Murine Model ◽

Systemic Disease ◽

Content Type ◽

E Coli ◽

Bacterial Genes ◽

Tract Infections ◽

K 12

ABSTRACTInfection with uropathogenicEscherichia coli(UPEC), the causative agent of most uncomplicated urinary tract infections, proceeds in an ascending manner and, if left untreated, may result in bacteremia and urosepsis. To examine the fate of UPEC after its entry into the bloodstream, we developed a murine model of sublethal bacteremia. CBA/J mice were inoculated intravenously with 1 × 106 CFU of pyelonephritis strainE. coliCFT073 carrying a bioluminescent reporter. Biophotonic imaging, used to monitor the infection over 48 h, demonstrated that the bacteria disseminated systemically and appeared to localize at discrete sites. UPEC was recovered from the spleen, liver, kidneys, lungs, heart, brain, and intestines as early as 20 min postinoculation, peaking at 24 h postinoculation. A nonpathogenicE. coliK-12 strain, however, disseminated at significantly lower levels (P< 0.01) and was cleared from the liver and cecum by 24 h postinoculation. Isogenic mutants lacking type 1 fimbriae, P fimbriae, capsule, TonB, the heme receptors Hma and ChuA, or particularly the sialic acid catabolism enzyme NanA were significantly outcompeted by wild-type CFT073 during bacteremia (P< 0.05), while flagellin and hemolysin mutants were not.IMPORTANCEE. coliis the primary cause of urinary tract infections. In severe cases of kidney infection, bacteria can enter the bloodstream and cause systemic disease. While the ability ofE. colito cause urinary tract infection has been extensively studied, the fate of these bacteria once they enter the bloodstream is largely unknown. Here we used an imaging technique to develop a mouse model ofE. colibloodstream infection and identify bacterial genes that are important for the bacteria to spread to and infect various organs. Understanding how urinary tract pathogens likeE. colicause disease after they enter the bloodstream may aid in the development of protective and therapeutic treatments.

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