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1.  Experimental model of corynebacterium renale pyelonephritis produced in mice. 
Infection and Immunity  1977;16(1):263-267.
Corynebacterium renale type I (strain 115), 1.7 X 10(7) to 4.5 X 10(7) organisms, introduced intravenously into mice disappeared from the blood less than 24 h after inoculation and did not produce pyelonephritis. The same strain, 1 X 10(7) to 5 X 10(7) organisms, inoculated into the urinary bladder of mice was not recovered from the blood in any of the mice, but caused pyelonephritis accompanied by ureteritis and cystitis in 16 of 21 (76%) mice. Pyelonephritis and cystitis in mice were histopathologically similar to those found in cows. The antibody response was observed only in the mice with pyelonephritis or pyelitis, but not in those with only cystitis or in those without lesions, as found in cows. Similar diseases were produced in mice by C. renale types II and III but less frequently than by type I. It is suggested, therefore, that mice may be useful in the study of bovine C. renale infection.
PMCID: PMC421517  PMID: 873610
2.  Comparison of Escherichia coli Strains Recovered from Human Cystitis and Pyelonephritis Infections in Transurethrally Challenged Mice 
Infection and Immunity  1998;66(7):3059-3065.
Urinary tract infection, most frequently caused by Escherichia coli, is one of the most common bacterial infections in humans. A vast amount of literature regarding the mechanisms through which E. coli induces pyelonephritis has accumulated. Although cystitis accounts for 95% of visits to physicians for symptoms of urinary tract infections, few in vivo studies have investigated possible differences between E. coli recovered from patients with clinical symptoms of cystitis and that from patients with symptoms of pyelonephritis. Epidemiological studies indicate that cystitis-associated strains appear to differ from pyelonephritis-associated strains in elaboration of some putative virulence factors. With transurethrally challenged mice we studied possible differences using three each of the most virulent pyelonephritis and cystitis E. coli strains in our collection. The results indicate that cystitis strains colonize the bladder more rapidly than do pyelonephritis strains, while the rates of kidney colonization are similar. Cystitis strains colonize the bladder in higher numbers, induce more pronounced histologic changes in the bladder, and are more rapidly eliminated from the mouse urinary tract than pyelonephritis strains. These results provide evidence that cystitis strains differ from pyelonephritis strains in this model, that this model is useful for the study of the uropathogenicity of cystitis strains, and that it would be unwise to use pyelonephritis strains to study putative virulence factors important in the development of cystitis.
PMCID: PMC108313  PMID: 9632566
3.  Detection of Streptococcus suis in Bioaerosols of Swine Confinement Buildings 
Applied and Environmental Microbiology  2014;80(11):3296-3304.
Streptococcus suis is an important swine pathogen that can cause septicemia, meningitis, and pneumonia. Also recognized as an emerging zoonotic agent, it is responsible for outbreaks of human infections in Asian countries. Serotype 2 is the predominant isolate from diseased animals and humans. The aerosolization of S. suis in the air of swine confinement buildings (SCB) was studied. The presence of S. suis in bioaerosols was monitored in SCB where cases of infection had been reported and in healthy SCB without reported infections. Using a quantitative-PCR (qPCR) method, we determined the total number of bacteria (1 × 108 to 2 × 108 airborne/m3), total number of S. suis bacteria (4 × 105 to 10 × 105 airborne/m3), and number of S. suis serotype 2 and 1/2 bacteria (1 × 103 to 30 × 103 airborne/m3) present in the air. S. suis serotypes 2 and 1/2 were detected in the air of all growing/finishing SCB that had documented cases of S. suis infection and in 50% of healthy SCB. The total number of bacteria and total numbers of S. suis and S. suis serotype 2 and 1/2 bacteria were monitored in one positive SCB during a 5-week period, and it was shown that the aerosolized S. suis serotypes 2 and 1/2 remain airborne for a prolonged period. When the effect of aerosolization on S. suis was observed, the percentage of intact S. suis bacteria (showing cell membrane integrity) in the air might have been up to 13%. Finally S. suis was found in nasal swabs from 14 out of 21 healthy finishing-SCB workers, suggesting significant exposure to the pathogen. This report provides a better understanding of the aerosolization, prevalence, and persistence of S. suis in SCB.
PMCID: PMC4018844  PMID: 24632262
4.  Genotypic Analysis of E. coli Strains Isolated from Patients with Cystitis and Pyelonephritis 
Urinary tract infection is the most common health problem affecting millions of people each year, mainly caused by a large genetically heterogeneous group of Escherichia coli called uropathogenic E. coli This study investigates the genotypic analysis of E. coli strains isolated from patients with cystitis and pyelonephritis.
During 2008-2009, 90 E. coli strains were analyzed, consisting of 48 isolates causing pyelonephritis in children and 42 isolates causing cystitis. Having identified the strains by standard methods, they were subtyped by pulsed field gel electrophoresis (PFGE) and their corresponding patterns were compared using dendrogram.
Sixty five PFGE profiles were obtained from the genome of E. coli strains by this genotyping method. Thirty six and thirty three patterns were obtained for pyelonephritis and cystitis, respectively. Most strains exhi-bited twelve and thirteen bands and the patterns with eight or nineteen bands had the lowest rate. Genome sizes of the strains were between 1610-4170 kbp.
With due attention to these results, genetic patterns showed that the strains had different clonalities and it could be suggested in some cases that the strains causing pyelonephritis or cystitis have common patterns and different diseases could be explained by different gene factors.
PMCID: PMC3438433  PMID: 22997556
Uropathogenic Escherichia coli; Pyelonephritis; Cystitis; Electrophoresis; Genetic patterns
1. It has been possible to demonstrate, in Berkefeld filtrates of infectious material from experimental cases of swine influenza, a virus which when administered intranasally to susceptible swine induced a mild, usually afebrile illness of short duration. The changes in the respiratory tract resembled those in swine influenza but were usually much less extensive. When the filtrable virus was mixed with pure cultures of H. influenzae suis and administered to swine a disease identical clinically and pathologically with swine influenza was induced. The data presented indicate that the filtrable virus of swine influenza and H. influenzae suis act in concert to produce swine influenza and that neither alone is capable of inducing the disease. 2. One attack of swine influenza usually renders an animal immune to reinfection. Blood serum from an animal made immune in this way neutralizes infectious material from swine influenza in vitro, as shown by the failure of the mixture to produce disease in a susceptible animal. 3. The virus can be stored in a dried state or in glycerol for several weeks at least. In one instance dried material apparently retained both the virus and H. influenzas suis in viable form for a period of 54 days. 4. Fatal cases of experimental swine influenza have been observed in which H. influenzae suis was the only organism that could be cultivated from the respiratory tract. 5. Attention has been called to some features of marked similarity between epizootic swine influenzae and epidemic influenzae in man.
PMCID: PMC2132000  PMID: 19869924
6.  Nutritional and metabolic features of Eubacterium suis. 
Journal of Clinical Microbiology  1982;15(5):895-901.
We studied the nutritional and metabolic features of Eubacterium suis, an anaerobic animal pathogen that causes cystitis and pyelonephritis in pigs. Peptone-yeast extract-starch (PYS) medium, which contained Trypticase (BBL Microbiology Systems), yeast extract, starch, minerals, cysteine, and sodium carbonate, was shown to support excellent growth of this organism (absorbance at 600 nm = 1.8). Growth was considerably less (absorbance at 600 nm = 0.6) when the starch in the medium was replaced by maltose. Formate, acetate, and ethanol were the major products of fermentation of starch or maltose. The organism appears to require a fermentable carbohydrate for growth since the deletion of starch from PYS resulted in a negligible amount of growth. Growth decreased by approximately 20% when CO2 was rigorously excluded from PYS minus Na2CO3. The deletion of only yeast extract from PYS resulted in a decrease in growth of about 75%, and the simultaneous deletion of both yeast extract and Trypticase resulted in negligible growth. When the yeast extract in PYS was replaced by a defined mixture of purine and pyrimidine bases, vitamins, and amino acids, growth was greater than or equal to 80% that observed in PYS. The deletion of Trypticase from this medium resulted in no detectable growth, suggesting a possible peptide requirement for E. suis growth. Good growth (absorbance at 600 nm = 1.4) was obtained when adenine and uracil were substituted for the mixture of purine and pyrimidine bases in modified PYS; the substitution of pyridoxal, riboflavin, and nicotinic acid for the vitamin mixture gave comparable growth. The nutritional requirement of E. suis apparently reflect the fact that the organism adapts to its natural niche by doing away with certain biosynthetic capabilities which it does not seem to require.
PMCID: PMC272210  PMID: 6808018
7.  Differences in Virulence Factors among Clinical Isolates of Escherichia coli Causing Cystitis and Pyelonephritis in Women and Prostatitis in Men 
Journal of Clinical Microbiology  2002;40(12):4445-4449.
Differences in the presence of nine urovirulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men have been studied. Hemolysin and necrotizing factor type 1 occur significantly more frequently among isolates causing prostatitis than among those causing cystitis (P < 0.0001) or pyelonephritis (P < 0.005). Moreover, the papGIII gene occurred more frequently in E. coli isolates associated with prostatitis (27%) than in those associated with pyelonephritis (9%) (P < 0.05). Genes encoding aerobactin and PapC occurred significantly less frequently in isolates causing cystitis than in those causing prostatitis (P < 0.01 and P < 0.0001, respectively) and pyelonephritis (P < 0.01 and P < 0.0001, respectively). No differences in the presence of Sat or type 1 fimbriae were found. Finally, AAFII and Bfp fimbriae are no longer considered uropathogenic virulence factors since they were not found in any of the strains analyzed. Overall, the results showed that clinical isolates producing prostatitis need greater virulence than isolates producing pyelonephritis in women or, in particular, cystitis in women (P < 0.05). Overall, the results suggest that clinical isolates producing prostatitis are more virulent that those producing pyelonephritis or cystitis in women.
PMCID: PMC154654  PMID: 12454134
8.  Family History and Risk of Recurrent Cystitis and Pyelonephritis in Women 
The Journal of urology  2010;184(2):564-569.
Recurrent urinary tract infections and pyelonephritis have risk factors suggesting genetic sources. Family history variables indicative of genetic risk merit further investigation. We evaluated the risk of recurrent cystitis and pyelonephritis in women with and those without a family history of urinary tract infection.
Materials and Methods
We conducted a population based case-control study of 1,261 women 18 to 49 years old enrolled in a Northwest health plan. Participants were cases identified from plan databases with documented recurrent cystitis (431) or pyelonephritis (400). Shared controls (430) were similar age women with no urinary tract infection history. We evaluated the history of urinary tract infection and pyelonephritis in first-degree female relatives (mother, sister[s], daughter[s]) and other covariates, ascertained through questionnaires and computerized databases.
Of the cases 70.9% with recurrent cystitis and 75.2% with pyelonephritis, and of the controls 42.4% reported a urinary tract infection history in 1 or more female relative (p <0.001 for each case group vs controls). In both case groups odds ratios were significantly increased for women reporting a urinary tract infection history in their mother, sister(s) or daughter(s). Risk increased with a greater number of affected relatives. In women with 1 vs 2 or more relatives the ORs for recurrent cystitis were 3.1 (95% CI 2.1, 4.7) and 5.0 (3.1, 8.1), and the ORs for pyelonephritis were 3.3 (2.2, 5.0) and 5.5 (3.4, 9.0), respectively.
In these community dwelling women a urinary tract infection history in female relatives was strongly and consistently associated with urinary tract infection recurrence and pyelonephritis. Risk estimates increased with stronger family history indices, suggesting a genetic component for increased susceptibility to these infections.
PMCID: PMC3665335  PMID: 20639019
urinary tract infections; epidemiology; pyelonephritis; female; case-control studies
9.  Bacterial Characteristics in Relation to Clinical Source of Escherichia coli Isolates from Women with Acute Cystitis or Pyelonephritis and Uninfected Women 
Journal of Clinical Microbiology  2005;43(12):6064-6072.
Characteristics differentiating Escherichia coli strains that cause cystitis or pyelonephritis from fecal E. coli remain incompletely defined, particularly among adult women in the United States. Accordingly, phylogenetic group, O antigens, and virulence factors (VFs) were analyzed among 329 E. coli isolates from the mid-to-late 1990s from women in the United States with acute pyelonephritis (n = 170), cystitis (n = 83), or no infection (fecal; n = 76). Compared with fecal and cystitis isolates, pyelonephritis isolates exhibited a greater prevalence of phylogenetic group B2, most virulence-associated O antigens, and most VFs and had higher VF scores. In contrast, cystitis and fecal isolates differed minimally. By stepwise multivariable logistic regression, significant (P ≤ 0.015) predictors of cystitis and/or pyelonephritis (versus fecal) included afa/dra (Dr-binding adhesins), ibeA (invasion of brain endothelium), iha (putative adhesin-siderophore), malX (pathogenicity island marker), the O75 antigen, papEF (P fimbriae), papG allele II (P adhesin variant), group B2, and sfa/foc (S and F1C fimbriae). However, virulence profiles overlapped considerably among source groups and varied greatly within each group. E. coli “clonal group A” (CGA) and the O2:K5/K7:H1 and O75:K+ clonal groups were significantly associated with cystitis and/or pyelonephritis. These findings identify potential vaccine targets, suggest that urovirulence is multiply determined, and confirm the urovirulence of specific E. coli clonal groups, including recently recognized CGA.
PMCID: PMC1317206  PMID: 16333100
10.  Medical and Infectious Complications Associated with Pyelonephritis among Pregnant Women at Delivery 
Objective. Pyelonephritis is a common cause of antepartum admission and maternal morbidity. Medical complications associated with pyelonephritis during delivery are not well described; thus the objective of this study was to estimate medical, infectious, and obstetric complications associated with pyelonephritis during the delivery admission. Study Design. We conducted a retrospective cohort study using the Nationwide Inpatient Sample (NIS) for the years 2008–2010. The NIS was queried for all delivery-related discharges. During the delivery admission, the ICD-9-CM codes for pyelonephritis were used to identify cases and were compared to women without pyelonephritis. A multivariable logistic regression model was constructed for various medical, infectious, and obstetric complications among women with pyelonephritis compared to women without, while controlling for preexisting medical conditions and demographics. Results. During the years 2008–2010, there were 26,397 records with a diagnosis of pyelonephritis during the delivery admission, for a rate of 2.1 per 1000 deliveries. Women with pyelonephritis had increased associated risks for transfusion, need for mechanical ventilation, acute heart failure, pneumonia, pulmonary edema, acute respiratory distress syndrome, sepsis, acute renal failure, preterm labor, and chorioamnionitis, while controlling for preexisting medical conditions. Conclusions. Pyelonephritis at delivery admissions is associated with significant medical and infectious morbidity.
PMCID: PMC3804393  PMID: 24194632
11.  Streptococcus suis Causes Septic Arthritis and Bacteremia: Phenotypic Characterization and Molecular Confirmation 
Streptococcus suis is a swine pathogen that causes meningitis, septicemia, pneumonia, and endocarditis. The first case of human S. suis infection was reported in Denmark in 1968, and since then, this infection with has been reported in many countries, especially in Southeast Asia because of the high density of pigs in this region. We report the case of a patient with septic arthritis and bacteremia caused by S. suis. Cases in which S. suis is isolated from the joint fluid are very rare, and to the best of our knowledge, this is first case report of S. suis infection in Korea. The identity of this organism was confirmed by phenotypic characterization and 16S rRNA sequence analysis. An 81-yr-old Korean woman who presented with fever, arthralgia, and headache was admitted to a secondary referral center in Korea. Culture of aspirated joint fluid and blood samples showed the growth of S. suis biotype II, which was identified by the Vitek2 GPI and API 20 Strep systems (bioMérieux, USA), and this organism was susceptible to penicillin G and vancomycin. The 16S rRNA sequences of the blood culture isolates showed 99% homology with those of S. suis subsp. suis, which are reported in GenBank. The patient's fever subsided, and blood and joint cultures were negative for bacterial growth after antibiotic therapy; however, the swelling and pain in her left knee joint persisted. She plans to undergo total knee replacement.
PMCID: PMC3115998  PMID: 21474987
Streptococcus suis; Arthritis; Bacteremia
12.  In Vivo Phase Variation of Escherichia coli Type 1 Fimbrial Genes in Women with Urinary Tract Infection 
Infection and Immunity  1998;66(7):3303-3310.
Type 1 fimbriae, expressed by most Escherichia coli strains, are thought to attach to human uroepithelium as an initial step in the pathogenesis of urinary tract infections (UTI). Numerous reports using both in vitro and murine models support this role for type 1 fimbriae in colonization. Unfortunately, only a limited number of studies have directly examined the expression of fimbriae in vivo. To determine whether type 1 fimbrial genes are transcribed during an acute UTI, we employed a modification of an established method. The orientation (ON or OFF) of the invertible promoter element, which drives transcription of type 1 fimbrial genes, was determined by PCR amplification using primers that flank the invertible element, followed by SnaBI digestion. The orientation of the type 1 fimbrial switch was determined under three experimental conditions. First, E. coli strains from different clinical sources (acute pyelonephritis patients, cystitis patients, and fecal controls) were tested under different in vitro culture conditions (agar versus broth; aerated versus static). The genes in the more-virulent strains (those causing acute pyelonephritis) demonstrated a resistance, in aerated broth, to switching from OFF to ON, while those in fecal strains readily switched from OFF to ON. Second, bladder and kidney tissue from CBA mice transurethrally inoculated with E. coli CFT073 (an established murine model of ascending UTI) was assayed. The switches directly amplified from infected bladder and kidney tissues were estimated to be 33 and 39% ON, respectively, by using a standard curve. Finally, bacteria present in urine samples collected from women with cystitis were tested for type 1 fimbria switch orientation. For all 11 cases, an average of only 4% of the switches in the bacteria in the urine were ON. In 7 of the 11 cases, we found that all of the visible type 1 fimbrial switches were in the OFF position (upper limit of detection of assay, 98% OFF). Strains recovered from these urine samples, however, were shown after culture in vitro to be capable of switching the fimbrial gene to the ON position and expressing mannose-sensitive hemagglutinin. The results from experimental infections and cases of cystitis in women suggest that type 1 fimbrial genes are transcribed both in the bladder and in the kidney. However, those bacteria found in the urine and not attached to the uroepithelium are not transcriptionally active for type 1 fimbrial genes.
PMCID: PMC108346  PMID: 9632599
1. During a 3 year study of the lungworm as intermediate host for the swine influenza virus 98 transmission experiments, using 216 swine, have been conducted. Of these, 50 gave negative results. In the remaining 48, transmission of swine influenza virus by way of the lungworm was demonstrated in one or more animals of each experiment. Irregularities in the results would appear to be due not so much to lack of transmission of masked virus by the lungworms as to failure to evoke its pathogenic capabilities. 2. The stimulus of choice that was most successful in the provocation of swine influenza consisted of multiple intramuscular injections of H. influenzae suis. In several experiments pigs developed swine influenza virus infections 9 to 17 days after infestation with infected lungworms in the absence of any known provocative stress. In these instances an immune response of the swine to the lungworms themselves is suspected of having furnished the provocation. 3. During May, June, July, and August, swine prepared by the ingestion of lungworms carrying virus were absolutely refractory to the provocation of influenza, and they were relatively refractory in September and October. The masked virus was activated most readily during the first 4 months of the year. 4. In a single experiment we succeeded in demonstrating by direct means the presence of swine influenza virus in the neighborhood of lungworms at the base of the lung at a time when the virus was not demonstrable anywhere else in the respiratory tract. 5. Masked swine influenza virus was found to be present in lungworm ova obtained either from the respiratory tracts or the feces of infected swine. 6. In a number of instances, masked swine influenza virus has been found to persist for over a year in lungworm larvae within the earthworm intermediate hosts, and in one case its presence was demonstrated after 32 months. 7. Two varieties of a single species of earthworm, namely, Allolobophora caliginosa f. typica (Savigny) and A. caliginosa f. trapezoides (Dugès), have been found separately capable of serving as intermediate hosts for virus-infected lungworms. 8. Lungworm ova, obtained from convalescent swine which are no longer carrying swine influenza virus in infectious form in their respiratory tracts, contain masked virus.
PMCID: PMC2135320  PMID: 19871268
Bacteriological examination of the genito-urinary tract of calves originating in a herd in which infectious cystitis and pyelonephritis exists among the cows, revealed a variety of cultural types of diphtheroids. Of these types, one obtained from a considerable number of the calves resembled in morphology and cultural characters the organism cultivated from the actual cases of the disease. This group had agglutination affinities like those of the organism mentioned and was capable of absorbing agglutinin from antiserum specific for it. When three cows were inoculated intra-urethrally with cultures isolated from the sheaths of calves, two developed transient infections and the other a severe prolonged cystitis and pyelonephritis.
PMCID: PMC2131856  PMID: 19869737
15.  Slaughterhouse Pigs Are a Major Reservoir of Streptococcus suis Serotype 2 Capable of Causing Human Infection in Southern Vietnam 
PLoS ONE  2011;6(3):e17943.
Streptococcus suis is a pathogen of major economic significance to the swine industry and is increasingly recognized as an emerging zoonotic agent in Asia. In Vietnam, S. suis is the leading cause of bacterial meningitis in adult humans. Zoonotic transmission is most frequently associated with serotype 2 strains and occupational exposure to pigs or consumption of infected pork. To gain insight into the role of pigs for human consumption as a reservoir for zoonotic infection in southern Vietnam, we determined the prevalence and diversity of S. suis carriage in healthy slaughterhouse pigs. Nasopharyngeal tonsils were sampled from pigs at slaughterhouses serving six provinces in southern Vietnam and Ho Chi Minh City area from September 2006 to November 2007. Samples were screened by bacterial culture. Isolates of S. suis were serotyped and characterized by multi locus sequence typing (MLST) and pulse field gel electrophoresis (PFGE). Antibiotic susceptibility profiles and associated genetic resistance determinants, and the presence of putative virulence factors were determined. 41% (222/542) of pigs carried S. suis of one or multiple serotypes. 8% (45/542) carried S. suis serotype 2 which was the most common serotype found (45/317 strains, 14%). 80% of serotype 2 strains belonged to the MLST clonal complex 1,which was previously associated with meningitis cases in Vietnam and outbreaks of severe disease in China in 1998 and 2005. These strains clustered with representative strains isolated from patients with meningitis in PFGE analysis, and showed similar antimicrobial resistance and virulence factor profiles. Slaughterhouse pigs are a major reservoir of S. suis serotype 2 capable of causing human infection in southern Vietnam. Strict hygiene at processing facilities, and health education programs addressing food safety and proper handling of pork should be encouraged.
PMCID: PMC3065462  PMID: 21464930
16.  Risk Factors Associated with Acute Pyelonephritis in Healthy Women 
Annals of internal medicine  2005;142(1):20-27.
Although most cases of acute pyelonephritis occur in otherwise healthy women, data on risk factors for this condition are lacking.
To evaluate infection characteristics, incidence, and risk factors associated with acute pyelonephritis in a sample of women.
Population-based case–control study.
Group Health Cooperative, a prepaid health plan in Washington.
788 nonpregnant women, 18 to 49 years of age. Case-patients (n = 242) were women with pyelonephritis who were identified from computerized databases. Controls were 546 similar-age women with no pyelonephritis diagnosis in the previous 5 years who were randomly selected from enrollment databases. Response rates for case-patients and controls were 73% and 64%, respectively.
Characteristics of infection and potential risk factors for pyelonephritis, ascertained through computer-assisted telephone interview and computerized databases.
7% of case-patients were hospitalized. Escherichia coli was the infecting pathogen in 85% of cases. In multivariable models, factors associated with pyelonephritis risk were frequency of sexual intercourse in the previous 30 days (odds ratio, 5.6 [95% CI, 2.8 to 11.0] for ≥3 times per week), recent urinary tract infection (UTI) (odds ratio, 4.4 [CI, 2.8 to 7.1]), diabetes (odds ratio, 4.1 [CI, 1.6 to 10.9]), recent incontinence (odds ratio, 3.9 [CI. 2.6 to 5.9]), new sexual partner in the previous year (odds ratio, 2.2 [CI, 1.4 to 3.6]), recent spermicide use (odds ratio, 1.7 [CI, 1.1 to 2.8]), and UTI history in the participant's mother (odds ratio, 1.6 [CI, 1.1 to 2.5]). Risk factors for selected subgroups (patients ≤ 30 years of age, patients > 30 years of age, patients with no UTI history, and inpatients) were also evaluated.
Potential recall bias, reliance on automated case definition criteria, and limited data on diabetes and incontinence variables.
Few nonpregnant, community-dwelling women younger than 50 years of age with pyelonephritis are hospitalized. As with cystitis in reproductive-age women, sexual behaviors and patient and family history of UTI are associated with increased pyelonephritis risk. Diabetes and incontinence also seem to independently increase the risk for pyelonephritis.
PMCID: PMC3722605  PMID: 15630106
17.  Prevalence of Pathogenicity Island IICFT073 Genes among Extraintestinal Clinical Isolates of Escherichia coli 
Journal of Clinical Microbiology  2005;43(5):2425-2434.
Uropathogenic Escherichia coli is the most common cause of urinary tract infection (UTI). Cystitis in women is by far the most common UTI; pyelonephritis in both sexes and prostatitis in men are more severe but are less frequent complaints. The ability of E. coli to cause UTI is associated with specific virulence determinants, some of which are encoded on pathogenicity islands (PAI). One such PAI (PAI IICFT073), of the prototypical uropathogenic E. coli strain CFT073, contains 116 open reading frames, including iron-regulated genes, carbohydrate biosynthetic genes, the serine protease autotransporter picU, a two-partner secretion system, a type I secretion system, mobility genes, and a large number of hypothetical genes. To determine the association of PAI IICFT073 with UTI, PCR was used to examine the prevalence of the five virulence-associated loci among the ECOR collection and a collection of E. coli isolated from patients with cystitis, pyelonephritis, prostatitis, or septicemia. All PAI IICFT073 loci were found to be more prevalent among the B2 phylogenetic group than any other group within the ECOR collection and among invasive prostatitis strains than were cystitis or pyelonephritis strains. These data support the theory that clinical isolates causing prostatitis are more virulent than those producing cystitis or pyelonephritis in women.
PMCID: PMC1153811  PMID: 15872276
18.  In Vivo Dynamics of Type 1 Fimbria Regulation in Uropathogenic Escherichia coli during Experimental Urinary Tract Infection 
Infection and Immunity  2001;69(5):2838-2846.
Escherichia coli is the primary cause of uncomplicated infections of the urinary tract including cystitis. More serious infections, characterized as acute pyelonephritis, can also develop. Type 1 fimbriae of E. coli contribute to virulence in the urinary tract; however, only recently has the expression of the type 1 fimbriae been investigated in vivo using molecular techniques. Transcription of type 1 fimbrial genes is controlled by a promoter that resides on a 314-bp invertible element capable of two orientations. One places the promoter in the ON orientation, allowing for transcription; the other places the promoter in the OFF orientation, preventing transcription. A PCR-based assay was developed to measure the orientation of the invertible element during an experimental urinary tract infection in mice. Using this assay, it was found that the percentage of the population ON in urine samples correlated with the respective CFU per gram of bladder (P = 0.0006) but not with CFU per gram of kidney (P > 0.069). Cystitis isolates present in the urine of mice during the course of infection had a higher percentage of their invertible elements in the ON orientation than did pyelonephritis isolates (85 and 34%, respectively, at 24 h; P < 0.0001). In general, cystitis isolates, unlike pyelonephritis isolates, were more likely to maintain their invertible elements in the ON orientation for the entire period of infection. E. coli cells expressing type 1 fimbriae, expelled in urine, were shown by scanning electron microscopy to be densely packed on the surface of uroepithelial cells. These results suggest that expression of type 1 fimbriae is more critical for cystitis strains than for pyelonephritis strains in the early stages of an infection during bladder colonization.
PMCID: PMC98232  PMID: 11292696
19.  Virulence of Escherichia coli in relation to host factors in women with symptomatic urinary tract infection. 
Journal of Clinical Microbiology  1988;26(8):1471-1476.
The relationship between bacterial characteristics and the severity of urinary tract infection in adults has not been clarified. In this study, Escherichia coli strains (n = 178) were prospectively collected from women with community-acquired urinary tract infection. The isolates were identified by O:K:H serotype and characterized for adherence, hemolysin production, and serum bactericidal resistance. The patients had acute pyelonephritis with or without complicating factors and acute cystitis. Nine serotypes (O1:K1:H7, O1:K1:H-, O2:K1:H-, O4:K12:H1, O7:K1:H-, O9:K34:H-, O16:K1:H6, O16:K1:H-, and O75:K5:H-) comprised 65% of the strains in uncomplicated pyelonephritis, but were significantly less often encountered in complicated pyelonephritis or cystitis. Adherence was the single property most characteristic of the pyelonephritogenic clones. Adhesins specifically recognizing Gal alpha 1----4Gal beta-containing receptors occurred in 80% of strains in uncomplicated pyelonephritis, in 50% of strains in complicated infections, and in 37% of cystitis strains. Hemolysin production and serum resistance did not correlate with any disease pattern. Advanced age did not seem to reduce the selection of virulent E. coli to cause pyelonephritis. These results demonstrate in women a relationship between E. coli virulence and the severity of urinary tract infection analogous to that previously observed in pediatric populations and also illustrate the balance between host resistance and bacterial virulence in the urinary tract.
PMCID: PMC266644  PMID: 3049654
20.  Group B streptococcus cystitis presenting in a diabetic patient with a massive abdominopelvic abscess: a case report 
Streptococcus agalactiae or group B streptococcus is a Gram-positive pathogen that is typically associated with neonatal disease and infection in pregnant women. Group B streptococcus also causes invasive infections in non-pregnant adults including urinary tract infections. The spectrum of urinary tract infections caused by group B streptococcus includes cystitis, pyelonephritis, urosepsis and asymptomatic bacteriuria, which is particularly common among elderly individuals. A rare form of invasive group B streptococcus infection in adults is secondary abscess. Here, we present the first reported case of a patient who developed an unusual, massive abdominopelvic abscess secondary to acute group B streptococcus urinary tract infection.
Case presentation
A 46-year-old African-American woman presented to the University Emergency Department complaining of urinary tract infection symptoms and severe abdominal pain. Diagnostic imaging by transvaginal ultrasound and computed tomography revealed a massive peripherally-enhancing, low-attenuating fluid collection within her pelvis. The patient’s abdominopelvic abscess was drained by ultrasound-guided drainage and this yielded a septic aspirate that was culture positive for abundant S. agalactiae. A recent history of urinary tract infection symptoms in the patient suggested that her abscess developed secondary to cystitis. Complete resolution of the abscess as a favorable outcome was achieved in this case following surgical drainage and appropriate antimicrobial therapy.
Acute bacterial urinary tract infection leading to an abdominopelvic abscess has not previously been reported in the literature. This case report defines a new disease etiology associated with acute streptococcal cystitis and it will be of interest in cases of urinary tract infections where there is an association with abdominal and/or pelvic pain. A brief review of the literature on unusual secondary abscesses due to group B streptococcus is provided alongside this case to highlight the clinical significance and prognoses of these rare infections. Finally, this case emphasizes the requirement to distinguish unusual etiologies of pyogenic abscesses in order to guide successful clinical management and to treat patients with antibiotics active against the causal organism.
PMCID: PMC3443647  PMID: 22883571
Abscess; Cystitis; Group B streptococcus; Streptococcus agalactiae; Urinary tract infection
21.  Transcriptional approach to study porcine tracheal epithelial cells individually or dually infected with swine influenza virus and Streptococcus suis 
Swine influenza is a highly contagious viral infection in pigs affecting the respiratory tract that can have significant economic impacts. Streptococcus suis serotype 2 is one of the most important post-weaning bacterial pathogens in swine causing different infections, including pneumonia. Both pathogens are important contributors to the porcine respiratory disease complex. Outbreaks of swine influenza virus with a significant level of co-infections due to S. suis have lately been reported. In order to analyze, for the first time, the transcriptional host response of swine tracheal epithelial (NPTr) cells to H1N1 swine influenza virus (swH1N1) infection, S. suis serotype 2 infection and a dual infection, we carried out a comprehensive gene expression profiling using a microarray approach.
Gene clustering showed that the swH1N1 and swH1N1/S. suis infections modified the expression of genes in a similar manner. Additionally, infection of NPTr cells by S. suis alone resulted in fewer differentially expressed genes compared to mock-infected cells. However, some important genes coding for inflammatory mediators such as chemokines, interleukins, cell adhesion molecules, and eicosanoids were significantly upregulated in the presence of both pathogens compared to infection with each pathogen individually. This synergy may be the consequence, at least in part, of an increased bacterial adhesion/invasion of epithelial cells previously infected by swH1N1, as recently reported.
Influenza virus would replicate in the respiratory epithelium and induce an inflammatory infiltrate comprised of mononuclear cells and neutrophils. In a co-infection situation, although these cells would be unable to phagocyte and kill S. suis, they are highly activated by this pathogen. S. suis is not considered a primary pulmonary pathogen, but an exacerbated production of proinflammatory mediators during a co-infection with influenza virus may be important in the pathogenesis and clinical outcome of S. suis-induced respiratory diseases.
PMCID: PMC4022123  PMID: 24708855
Streptococcus suis; Swine Influenza virus; Co-infection; Microarray; Cytokines/chemokines induction; Porcine tracheal epithelial cells
22.  Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection 
PLoS Medicine  2007;4(12):e329.
Urinary tract infections (UTIs) are one of the most common bacterial infections and are predominantly caused by uropathogenic Escherichia coli (UPEC). While UTIs are typically considered extracellular infections, it has been recently demonstrated that UPEC bind to, invade, and replicate within the murine bladder urothelium to form intracellular bacterial communities (IBCs). These IBCs dissociate and bacteria flux out of bladder facet cells, some with filamentous morphology, and ultimately establish quiescent intracellular reservoirs that can seed recurrent infection. This IBC pathogenic cycle has not yet been investigated in humans. In this study we sought to determine whether evidence of an IBC pathway could be found in urine specimens from women with acute UTI.
Methods and Findings
We collected midstream, clean-catch urine specimens from 80 young healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a history of UTI. Investigators were blinded to culture results and clinical history. Samples were analyzed by light microscopy, immunofluorescence, and electron microscopy for evidence of exfoliated IBCs and filamentous bacteria. Evidence of IBCs was found in 14 of 80 (18%) urines from women with UTI. Filamentous bacteria were found in 33 of 80 (41%) urines from women with UTI. None of the 20 urines from the asymptomatic comparative group showed evidence of IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with IBCs compared to 19 (29%) of 66 samples with no evidence of IBCs (p < 0.001). Of 65 urines from patients with E. coli infections, 14 (22%) had evidence of IBCs and 29 (45%) had filamentous bacteria, while none of the gram-positive infections had IBCs or filamentous bacteria.
The presence of exfoliated IBCs and filamentous bacteria in the urines of women with acute cystitis suggests that the IBC pathogenic pathway characterized in the murine model may occur in humans. The findings support the occurrence of an intracellular bacterial niche in some women with cystitis that may have important implications for UTI recurrence and treatment.
Analyzing urine specimens from women with bladder infections, Scott Hultgren and colleagues find evidence for intracellular bacterial communities, which have been associated with recurrent urinary tract infections in mice.
Editors' Summary
Every year, nearly 10 million people in the United States—mainly women—consult their doctors because of a urinary tract infection (UTI). UTIs occur when bacteria living in the gut—usually Escherichia coli—get transferred to the opening of the urethra (the tube through which urine leaves the body), as may occur during sexual intercourse. From here, the bacteria can move into the bladder (the muscular sac that stores urine until it is excreted) where they can multiply and cause cystitis (inflammation of the bladder). If cystitis is untreated, the bacteria can move further up the urinary tract and infect the kidneys (which make urine). Symptoms of UTIs include pain when urinating, frequent and intense urges to urinate, and cloudy urine. UTIs are diagnosed by looking for bacteria and white blood cells (that fight infection) in the urine; the usual treatment is a short course of antibiotics.
Why Was This Study Done?
Half the women who get a UTI will have another attack within a year, often caused by the same bacterial strain. It is generally thought that these strains persist in the gut and reinfect the urinary tract, but recent animal studies suggest an additional explanation. In mice, E. coli strains that cause UTIs can invade the cells lining the bladder. Here, they replicate and form so-called intracellular bacterial communities (IBCs). Many of the infected cells fall off the bladder's surface into the urine, but IBCs also release bacteria, many of which have a long, slender filamentous appearance (E. coli usually have a simple rod-like shape). Immune system cells normally kill bacteria in the urine but cannot deal with filamentous bacteria. In mice, these bacteria can then reinfect the lining of the bladder and establish long-lasting intracellular reservoirs of bacteria that are protected from antibiotics and probably from the host immune system. If this IBC cycle occurs in people, it might explain why some UTIs recur and might suggest ways to manage these recurrences. In this study, therefore, the researchers have investigated whether there is an IBC cycle in women.
What Did the Researchers Do and Find?
The researchers collected urine from 80 young women with cystitis and from 20 women with no symptoms who had had cystitis previously. They identified the type of bacteria in each sample and looked for IBCs and filamentous bacteria using light microscopy, electron microscopy, and a technique called immunofluorescence. None of the women without cystitis had IBCs or filamentous bacteria in their urine, but IBCs were found in nearly 1 in 5, and filamentous bacteria were in nearly half, of urine samples from the women with cystitis. All the urine samples that contained IBCs also contained filamentous bacteria. All of the women with IBCs and most of them with filamentous bacteria had E coli infections. Finally, the women with IBCs and filamentous bacteria in their urine had higher bacterial counts in their urine and had symptoms of cystitis for slightly longer than those without.
What Do These Findings Mean?
These findings suggest that the IBC cycle identified in mice occurs in at least some women with UTIs and may be associated with infections caused by E. coli. Because only one urine sample was collected from each woman, the cycle may be more common than these findings suggest. That is, in some cases the sample may have been taken at a time when there were no IBCs or filamentous bacteria in the urine. Also, because samples were taken at only one point in time, this study does not show whether intracellular bacteria persist and contribute to recurrent UTIs in women, as they appear to do in mice. To provide more information about the IBC cycle in people and its clinical relevance, additional studies are needed to examine whether there are any associations between the presence of IBCs and filamentous bacteria and treatment responses and recurrence, and to examine what is actually happening in the bladder during UTI. Until such studies are done, the clinical implications of the current findings remain uncertain. However, one possibility is that the presence of IBCs and filamentous bacteria in urine might identify people who would benefit from longer treatment with antibiotics or treatment with antibiotics that kill bacteria inside human cells.
Additional Information.
Please access these Web sites via the online version of this summary at
The MedlinePlus encyclopedia contains pages on urinary tract infection, on cystitis, and on recurrent cystitis (in English and Spanish)
Information is available from the UK National Health Service Direct health encyclopedia on urinary tract infections and on cystitis
The US National Kidney and Urologic Diseases Information Clearinghouse provides information on urinary tract infections (in English and Spanish)
Information is available from the American Urological Association on urinary tract infections in adults
PMCID: PMC2140087  PMID: 18092884
23.  Deregulated Balance of Omega-6 and Omega-3 Polyunsaturated Fatty Acids following Infection by the Zoonotic Pathogen Streptococcus suis 
Infection and Immunity  2014;82(5):1778-1785.
Streptococcus suis is an important swine pathogen and an emergent zoonotic pathogen. Excessive inflammation caused by S. suis is responsible for early high mortality in septic shock-like syndrome cases. Polyunsaturated fatty acids (PUFAs) may contribute to regulating inflammatory processes. This study shows that mouse infection by S. suis is accompanied by an increase of arachidonic acid, a proinflammatory omega-6 (ω-6) PUFA, and by a decrease of docosahexaenoic acid, an anti-inflammatory ω-3 PUFA. Macrophages infected with S. suis showed activation of mitogen-activated protein kinase pathways and cyclooxygenase-2 upregulation. Fenretinide, a synthetic vitamin A analog, reduced in vitro expression of inflammatory mediators. Pretreatment of mice with fenretinide significantly improved their survival by reducing systemic proinflammatory cytokines during the acute phase of an S. suis infection. These findings indicate a beneficial effect of fenretinide in diminishing the expression of inflammation and improving survival during an acute infection by a virulent S. suis strain.
PMCID: PMC3993453  PMID: 24549326
24.  Emphysematous Cystitis: Report of an Atypical Case 
Case Reports in Urology  2011;2011:280426.
We report the atypical case of a nondiabetic 66-year old male with severe abdominal pain and vomiting who was found to have emphysematous cystitis. Of all gas-forming infections of the urinary tract emphysematous cystitis is the most common and the least severe. The major risk factors are diabetes mellitus and urinary tract obstruction. Most frequent causative pathogens are Escherichia coli and Klebsiella pneumoniae. The clinical presentation is nonspecific and ranges from asymptomatic urinary tract infection to urosepsis and septic shock. The diagnosis is made by abdominal imaging. Treatment consists of broad-spectrum antibiotics, bladder drainage, and management of the risk factors. Surgery is reserved for severe cases. Overall mortality rate of emphysematous cystitis is 7%. Immediate diagnosis and treatment is necessary because of the rapid progression to bladder necrosis, emphysematous pyelonephritis, urosepsis, and possibly fatal evolution.
PMCID: PMC3350004  PMID: 22606608
25.  Escherichia coli K5 antigen in relation to various infections and in healthy individuals. 
Journal of Clinical Microbiology  1984;19(2):264-266.
A phage specific for Escherichia coli K5 antigen was used to determine the frequency of K5 in strains of E. coli isolated from cases of sepsis, meningitis, and urinary tract infection (pyelonephritis, cystitis, and asymptomatic bacteriuria), as well as from fecal samples of healthy subjects. Although entirely absent from meningitic strains, K5 was found to be one of the most common E. coli capsular antigens, especially in strains causing sepsis. K5 was less common in the fecal strains of healthy subjects than in strains causing various urinary tract infections, between which there was no significant difference in its frequency. Thus, even if K5 is a less important antigen than K1 in the etiology of acute pyelonephritis or acute meningitis, as the fifth most commonly occurring K antigen in E. coli strains causing urinary tract infection it should be included as a component in any K antigen-based vaccine against acute pyelonephritis.
PMCID: PMC271034  PMID: 6199369

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