Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis / 亚洲男科学杂志(英文版)

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

ß-lactamasas de espectro extendido y factores de virulencia en Escherichia coli uropatógenas en asilos de ancianos en Lima, Perú / ß-lactamases and virulence factors in uropathogenic Escherichia coli in nursing homes in Lima, Peru

RESUMEN Los asilos de ancianos son instituciones con una alta prevalencia de infecciones del tracto urinario ocasionado por Escherichia coli productoras de ß-lactamasas de espectro extendido (BLEE), con diversos factores de virulencia. El objetivo del estudio fue determinar la frecuencia del gen bla CTX-M y de ocho genes de virulencia en 35 E. coli uropatógenas productoras de BLEE provenientes de seis asilos en Perú, durante el 2018. El 57,1% (20/35) de las E. coli fueron portadores del gen bla CTX-M. Además, se obtuvo una frecuencia del 46% (15/35) y 37% (13/35) de hly-alfa y cnf-1, respectivamente; elevada presencia de los genes iucC (63%, 22/35), aer (94%, 33/35) y chuA (94%, 33/34) y una frecuencia del 46% (16/35) y del 91% (32/34) de los genes pap GII y nanA, respectivamente. Existe predominancia en la distribución del gen bla CTX-M, además de una alta frecuencia de exotoxinas que le confieren una ventaja competitiva para diseminarse hacia el torrente sanguíneo.

ABSTRACT Nursing homes are institutions with high prevalence of urinary tract infections caused by ESBL-producing E. coli with several virulence factors. The aim of this study was to determine the frequency of the bla CTX-M gene and eight virulence genes in 35 ESBL-producing uropathogenic E. coli from six nursing homes in Peru during 2018. Of the E. coli samples, 57.1% (20/35) were carriers of the bla CTX-M gene. Furthermore, we obtained frequencies of 46% (15/35) and 37% (13/35) for hly-alpha and cnf-1, respectively; we also found high presence of the iucC (63%, 22/35), aer (94%, 33/35) and chuA genes (94%, 33/34) as well as a frequency of 46% (16/35) and 91% (32/34) for the pap GII and nanA genes, respectively. The bla CTX-M gene is predominant and a high frequency of exotoxins gives it a competitive advantage for spreading into the bloodstream.

Resistencia antimicrobiana de uropatógenos en adultos mayores / Antimicrobial resistance of uropathogens in older adults

Introducción: En la actualidad, la resistencia antimicrobiana ha sido declarada por la Organización Mundial de la Salud como un problema de salud pública. Objetivo: Determinar el perfil de resistencia antimicrobiana de uropatógenos en adultos mayores. Métodos: Estudio descriptivo transversal de 567 urocultivos positivos de adultos mayores atendidos durante el año 2017 en una clínica privada en Lima, Perú. El análisis univariado se realizó por distribución de frecuencias, promedio y desviación estándar. Se estimó la asociación entre la producción de BLEE con respecto a las características epidemiológicas y el tipo de atención mediante Chi cuadrado con un nivel de significación de 0,05. Resultados: La edad promedio de la población fue de 74,1 años (DE:10,7). El 71,8 por ciento de los urocultivos positivos pertenecieron al sexo femenino. Los principales uropatógenos aislados en todos los niveles de atención fueron: E. coli, E. coli BLEE y K. pneumoniae BLEE. La E. coli presentó 69,3 por ciento de resistencia a ampicilina; y la E. coli BLEE tuvo el 100 por ciento de resistencia a ampicilina, ceftriaxona y ceftazidima. El 62 por ciento de microorganismos BLEE se encontraron en la atención ambulatoria. Se evidenció asociación estadísticamente significativa entre los agentes productores de BLEE y el sexo (p=0,004), mas no respecto al tipo de atención (p=0,144) ni subgrupos de edad (p=0,669). Conclusiones: La resistencia antimicrobiana es altamente prevalente en los adultos mayores. El sexo femenino fue el más afectado y el uropatógeno más frecuente la E. coli, este presenta una alta resistencia a ampicilina y mayor sensibilidad a nitrofurantoína. Se determinó un alto porcentaje de agentes productores de BLEE en la atención ambulatoria(AU)

Introduction: At present, the World Health Organization as a public health problem has declared antimicrobial resistance. Objective: To determine the antimicrobial resistance profile of uropathogens in older adults. Methods: Cross-sectional descriptive study of 567 positive urine cultures from older adults treated during 2017 in a private clinic in Lima, Peru. Univariate analysis was performed by frequency distribution, mean and standard deviation. The association between ESBL production with respect to epidemiological characteristics and type of care is estimated using Chi square with a significance level of 0.05. Results: The average age of the population was 74.1 years (SD: 10.7). 71.8percent of the positive urine cultures were from female sex. The main uropathogens isolated at all levels of care were E. coli, E. coli ESBL and K. pneumoniae ESBL. E. coli showed 69.3percent resistance to ampicillin; and E. coli ESBL had 100percent resistance to ampicillin, ceftriaxone, and ceftazidime. 62percent of ESBL microorganisms were found in outpatient care. There was a statistically significant association between ESBL-producing agents and gender (p = 0.004), but not with regard to type of care (p = 0.144) or age subgroups (p = 0.669). Conclusions: Antimicrobial resistance is highly prevalent in older adults. The female sex was the most affected and the most frequent uropathogen was E. coli, highly resistant to ampicillin and greater sensitivity to nitrofurantoin. High percentage of ESBL-producing agents was determined in outpatient care(AU)

Caracterización microbiológica y molecular de la resistencia antimicrobiana de Escherichia coli uropatógenas de hospitales públicos peruanos / Microbiological and molecular characterization of antimicrobial resistance in uropathogenic Escherichia coli from peruvian public hospitals

RESUMEN Se caracterizó la resistencia antimicrobiana de 70 aislados de Escherichia coli obtenidos de pacientes con infección del tracto urinario (ITU) provenientes de ocho hospitales públicos en el Perú. Los perfiles de resistencia fueron identificados mediante el uso del sistema automatizado MicroScan®. Se utilizó una reacción en cadena de la polimerasa convencional para la detección de los genes bla TEM, bla CTX-M, bla SHV y bla PER. El 65,7% (46/70) de los aislados presentó un fenotipo multidrogorresistente y el 55,7% (39/70) fue identificado como productores de betalactamasas de espectro extendido. Se detectaron altos niveles de resistencia para ampicilina (77,1%), ciprofloxacina (74,3%), trimetoprim/sulfametoxazol (62,9%), cefepime (57,1%) y cefuroxima (57,1%). El gen bla TEM fue el más frecuente con un 31,4%, seguido por bla CTX-M (18,6%) y bla SHV (2,9%). Los resultados evidencian altos niveles de resistencia a antimicrobianos de importancia clínica en aislados de E. coli de pacientes con ITU en el Perú.

ABSTRACT We characterized the antimicrobial resistance of 70 Escherichia coli isolates obtained from patients with a urinary tract infection (UTI) from 8 public hospitals in Peru. Resistance profiles were identified using the automated MicroScan® system. A standard polymerase chain reaction was used for the detection of the bla TEM, bla CTX-M, bla SHV and bla PER genes. The 65.7% (46/70) of the isolates presented a multidrug-resistant phenotype and 55.7% (39/70) were extended-spectrum beta-lactamases producers. High levels of resistance were detected for ampicillin (77,1%), ciprofloxacin (74,3%), trimethoprim/sulfamethoxazole (62,9%), cefepime (57,1%), and cefuroxime (57,1%). The bla TEM gene was the most frequent (31,4%), followed by bla CTX-M (18,6%) and bla SHV (2,9%) genes. These results show high resistance levels to antimicrobials of clinical use in E. coli isolates from hospital UTI patients in Peru.

Respuesta inmunológica y bioquímica de ancianos con infección urinaria frente factores de virulencia en Escherichia coli uropatógenas / Immunological and biochemical response of older adults with urinary tract infection to uropathogenic Esherichia coli virulence factors

RESUMEN Con el objetivo de evidenciar diferencias en la respuesta inmunológica y bioquímica de ancianos con infección del tracto urinario (ITU) por Escherichia coli (E. coli) frente a factores de virulencia de importancia en la patogenia de la ITU, se realizó un estudio descriptivo en el cual se evaluaron 24 muestras de orina de adultos mayores con ITU provenientes de centros de reposo gerontológicos. Se determinó la concentración de hierro, TNF-α, IL-1β y la capacidad antioxidante en la orina, encontrándose una relación entre una mayor concentración de hierro y de hematíes en la orina con la presencia del gen pap GII en la E. coli. Se concluye que los adultos mayores con ITU por E. coli portadoras del gen pap GII, presentan mayor daño tisular.

ABSTRACT Descriptive study in which 24 urine samples from older adults with urinary tract infection (UTI), from nursing homes, were evaluated; in order to identify differences in the immune and biochemical response from older adults with UTI by Escherichia coli (E. coli) to major virulence factors in the pathogenesis of UTI. Iron concentration, TNF-α, IL-1β and antioxidant capacity in urine were determined. A relation was found between, an increase in iron and red blood cell concentration in urine, and the presence of the pap GII gene found in E. coli. It is concluded that older adults, with UTIs by E. coli with the gene pap GII, have increased tissue damage.

Distribución de grupos filogenéticos, factores de virulencia y susceptibilidad antimicrobiana en cepas de Escherichia coli uropatógena / Distribution of phylogenetic groups, virulence factors and antimicrobial susceptibility in strains of uropathogenic Escherichia coli

Resumen Introducción: La diferencia entre los aislados patógenos y comensales de Escherichia coli se fundamenta en sus antecedentes filogenéticos. En Venezuela son escasos los estudios que describen el potencial patogénico de los grupos filogenéticos en E. coli. Objetivo: Relacionar la susceptibilidad antimicrobiana, distribución de los grupos filogenéticos y genes de virulencia en cepas de E. coli uropatógena (ECUP) aisladas de pacientes con infección del tracto urinario. Materiales y Métodos: Se estudiaron 17 cepas de ECUP, aisladas de pacientes adultos hospitalizados en dos instituciones de salud. La susceptibilidad frente a ocho antimicrobianos se determinó por el método de microdilución en caldo (MDC). Las β-lactamasas de espectro extendido (BLEE) y carbapenemasas fueron detectadas fenotípicamente. Los grupos filogenéticos y la detección de los genes de virulencia se determinaron por reacción de polimerasa en cadena. Resultados: Todas las cepas sintetizaban BLEE y de éstas, 41% se asoció a la producción de una carbapenemasa (KPC o MBL). El filogrupo B2 (41%) fue predominante. Los genes de virulencia más frecuentes fueron fimH y fyuA con 82% cada uno. Sólo un aislado clasificado en el filogrupo F fue positivo al conjunto de seis genes estudiados. Discusión: La diversidad de asociaciones entre genes de virulencia y perfiles de resistencia, en las cepas ECUP evolucionan continuamente. Además, su distribución en los distintos grupos filogenéticos depende en gran medida de las características clínico epidemiológicas de los grupos de estudios.

Abstract Background: The difference between the pathogenic isolates and commensals of Escherichia coli is based on their phylogenetic antecedents. In Venezuela there are few studies that describe the pathogenic potential of phylogenetic groups in E. coli. Aims: Relate antimicrobial susceptibility, distribution of phylogenetic groups and virulence genes in strains of uropathogenic E. coli (ECUP) isolated from patients with UTI. Methods: We studied 17 ECUP strains, isolated from adult patients hospitalized in two health institutions. The susceptibility to 8 antibiotics was determined by the broth microdilution (MDC) method. Extended spectrum β-lactamases (ESBL) and carbapenemases were phenotypically detected. The phylogenetic groups and the detection of the virulence genes were determined by PCR. Results: All strains synthesized ESBL and of these, 41% were associated with the production of a carbapenemases (KPC or MBL). The phylogroup B2 (41%) was the most predominant. The most frequent virulence genes were fimH and fyuA with 82% each. Only one strain from group F was positive to the 6 genes studied. Discussion: The diversity of associations between virulence genes and resistance profiles in the ECUP are evolving continuously, their distribution in the different phylogenetic groups depends to a large extent on the clinical epidemiological characteristics of the study groups.

Outcome of acute urinary tract infections caused by uropathogenic Escherichia coli with phenotypically demonstrable virulence factors

Background: Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) strains is one of the most important community-acquired infections in the world. The presence of virulence factors is closely related with the pathogenesis of UTI. Methods: The present study was conducted on 150 isolates of UPEC obtained from symptomatic and asymptomatic cases of UTIs with significant counts (≥105 CFU/ml) during 1 year. UPEC isolates were studied for hemolysis on 5% sheep blood agar, mannose-sensitive hemagglutination (MSHA), mannose-resistant hemagglutination (MRHA), and biofilm formation by recommended methods. Patients with UTI due to UPEC showing virulence factors were evaluated for the treatment received and the outcome of treatment. These were compared with the outcomes of patients whose culture samples grew UPEC without demonstrable virulence factors. Results: The study showed hemolysin production in 40% of the isolates. Forty percent of the isolates showed the presence of P fimbriae (MRHA) and 60% showed Type 1 fimbriae (MSHA). Biofilm formation capacity of all UPEC isolates was classified into three categories, strong biofilm producers (4%), moderate biofilm producers (88%), and nonbiofilm producers (8%). Patients harboring all three virulence factors showed 76% recovery compared to patients harboring strains with no demonstrable virulence factors, who showed 100% recovery. Conclusion: The present study has shown the production of various virulent factors and developing drug resistance in UPEC. Treatment outcomes of patients harboring strains with no virulence factors seem to be better than the ones which contain multiple virulence factors. UPEC occurs because of multiple virulence factors. Biofilm formation and MRHA are more likely to be seen in catheterized patients. The drug resistance among UPEC is on rise; therefore, the selection of appropriate antibiotics (after antibiotic susceptibility testing) is must for proper treatment of patients and to avoid emergence of drug resistance. Significant number of the UPEC isolates was sensitive to nitrofurantoin, and half of the isolates were sensitive to cotrimoxazole, so treatment is by giving these drugs orally

Patogenia. Factores de riesgo en Diabetes Mellitus / Pathogenesis. Risk factors in diabetes mellitus

La interacción entre uroepitelio y uropatógeno, base de la patogenia de las infecciones del tracto urinario (ITUs), puede derivar en la eliminación bacteriana por parte de la célula huésped o la invasión y multiplicación bacteriana. Dentro de la célula huésped los uropatógenos pueden perturbar las defensas y resistir el tratamiento antibiótico. En pacientes con diabetes, especialmente con enfermedad renal por diabetes, se ha demostrado una reducción de la capacidad de inhibición de la adherencia bacteriana al uroepitelio, por ende mayor posibilidad de invasión bacteriana. La glicosilación de todos los elementos del sistema inmune, incluida la menor liberación de factores como las interleuquinas a nivel urinario y la alteración del vaciamiento vesical por neuropatía autonómica, favorecen el desarrollo de este tipo de infecciones

Interaction between urothelium and uropathogen, the basis of the pathogenesis of urinary tract infections (UTIs), can lead to bacterial elimination by the host cell or bacterial invasion and multiplication. Inside the host cell, uropathogens can impair defenses and resist antibiotic treatment. In patients with diabetes, especially diabetes-related kidney disease, a reduction in the inhibition capacity of bacterial adherence to the urothelium has been demonstrated; therefore, a highest chance of bacterial invasion. The glycosylation of all elements of the immune system, including the lower release of factors such as interleukins at the urinary level and the impairment of bladder emptying by autonomic neuropathy, enhance the development of this type of infections

Resistencia y sensibilidad bacteriana en urocultivos en una población de mujeres de ecuador / Bacterial resistance and sensitivity in urine cultures in a women population in ecuador / Resistência e sensibilidade bacteriana em uroculturas numa população de mulheres do equador

Resumen Objetivo: Determinar la prevalencia de uropatógenos, sensibilidad y resistencia antimicrobiana en la infección del tracto urinario que acuden al Hospital Básico Privado "Provida" del 1 de enero de 2014 al 31 de diciembre de 2016. Material y métodos: Se analizaron los resultados de 116 urocultivos de orina en mujeres no gestantes de todas las edades de 2014 a 2016, que fueron atendidas en el Hospital Básico Privado "Provida" de la cuidad de Latacunga, en Ecuador. El análisis de los datos obtenidos se realizó mediante estadística descriptiva. Resultados: De las 116 muestras, se aislaron: Escherichia coli (84,5%), Staphylococcus saprophyticus (8,6%) y Proteus spp. (6,9%). E. coli mostró sensibilidad a ceftriaxona en el 70 %, seguido de fosfomicina y gentamicina con el 62 y el 60%, respectivamente. La sensibilidad hallada para quinolonas fue del 40% y la ampicilina sulbactam alcanzó el 37%. Proteus spp. mostró sensibilidad del 75% para gentamicina y del 50% para quinolonas y cefuroxima. S. saprophyticus tuvo sensibilidad superior al 50% para gentamicina, ampicilina sulbactam, quinolonas y nitrofurantoína. Para E. coli la resistencia más alta registrada fue con ampicilina en el 86,5%, seguido de las quinolonas con una resistencia superior al 50%. La ampicilina asociada a inhibidor de betalactamasas, fosfomicina, cefalosporinas, nitrofurantoína y aminoglucósidos mostró resistencia inferior al 25%. Conclusión: El agente patógeno más prevalente en infecciones del tracto urinario (ITU) es E. coli (84,7%), porcentaje coincidente con lo reportado en la literatura nacional y mundial. Los antimicrobianos para este uropatógeno con mayor resistencia fueron ampicilina (86%), cirprofloxacina (55%) y norfloxacina (53%). Se podría tener en cuenta en el momento de administrar una terapéutica empírica, dato que debería ser corroborado con información de susceptibilidades de acuerdo con el contexto.

Summary Objective: To determine the prevalence of uropathogens, sensitivity and antimicrobial resistance in urinary tract infections that go to the Private Basic Hospital "Provida" from January 1, 2014 to December 31, 2016. Material and methods: The results of 116 urine cultures in non-pregnant women of all ages from 2014 to 2016, which were treated at the Private Basic Hospital "Provida" of the city of Latacunga, in Ecuador, were analyzed. The data obtained was analyzed using descriptive statistics. Results: In the 116 samples, Escherichia coli (84.5%), Staphylococcus saprophyticus (8.6%) and Proteus spp. (6.9%) were isolated. E. coli showed sensitivity to ceftriaxone in 70%, followed by fosfomycin and gentamicin with 62 and 60%, respectively. The sensitivity found for quinolones was 40% and for sulbactam ampicillin reached a 37%. Proteus spp. showed sensitivity of 75% for gentamicin and 50% for quinolones and cefuroxime. S. saprophyticus had a sensitivity greater than 50% for gentamicin, sulbactam ampicillin, quinolones and nitrofurantoin. For E. coli the highest resistance recorded was found on ampicillin in 86.5%, followed by quinolones with a resistance greater than 50%. Ampicillin associated with inhibitor of beta-lactamase, fosfomycin, cephalosporins, nitrofurantoin and aminoglycosides showed a resistance below 25%. Conclusion: The most prevalent pathogen in urinary tract infections (UTI) is E. coli (84.7%), a percentage that matches what has been reported in national and world literature. The antimicrobials for this uropathogen with the highest resistance were ampicillin (86%), ciprofloxacin (55%) and norfloxacin (53%). This should be taken into account when administering an empiric therapy, even though this data should be corroborated with the susceptibility information depending on the context.

Resumo Objetivo: Determinar a prevalência de uropatógenos, sensibilidade e resistência antimicrobiana na infecção do trato urinário que vão ao Hospital Básico Privado "Provida" de 1 de janeiro de 2014 a 31 de dezembro de 2016. Material e métodos: Analisaram-se os resultados de 116 uroculturas de urina em mulheres não gestantes de todas as idades de 2014 a 2016, que foram atendidas no Hospital Básico Privado "Provida" da cidade de Latacunga, no Equador. A análise dos dados obtidos realizou-se mediante estatística descritiva. Resultados: Das 116 amostras, isolaram-se: Escherichia coli (84,5%), Staphylococcus saprophyticus (8,6%) e Proteus spp. (6,9%). E. coli mostrou sensibilidade a ceftriaxona em 70 %, seguido de fosfomicina e gentamicina com 62 e 60%, respectivamente. A sensibilidade encontrada para quinolonas foi de 40% e a ampicilina sulbactam atingiu 37%. Proteus spp. mostrou sensibilidade de 75% para gentamicina e de 50% para quinolonas e cefuroxima. S. saprophyticus teve sensibilidade superior a 50% para gentamicina, ampicilina sulbac-tam, quinolonas e nitrofurantoína. Para E. coli a resistência mais alta registrada foi com ampicilina em 86,5%, seguido das quinolonas com uma resistência superior a 50%. A ampicilina associada a inibidor de betalactamasas, fosfomicina, cefalosporinas, nitrofurantoína e aminoglucósidos mostrou resistência inferior a 25%. Conclusão: O agente patogénico mais prevalente em infecções do trato urinário (ITU) é E. coli (84,7%), porcentagem coincidente com o apresentado na literatura nacional e mundial. Os antimicrobianos para esse uropatógeno com maior resistência foram ampicilina (86%), cirprofloxacina (55%) e norfloxacina (53%). Poderia ser tido em conta no momento de administrar uma terapêutica empírica, dado que deveria ser corroborado com informação de suscetibilidades de acordo com o contexto.

Sensibilidad a nitrofurantoína en el uropatógeno intrahospitalario E. Coli procedente de pacientes gerontes hospitalizados / Snsitivity to nitrofurantoin of urocultures from hospitalized gerontes with E. Coli from urinary tract infections

En la presente investigación se determinó la sensibilidad a nitrofurantoína (NTF) mediante un análisis observacional retrospectivo de informes de antibiogramas, por disco de difusión, de urocultivos provenientes de gerontes hospitalizados. En la serie observada (N=90) el desarrollo más frecuente fue E. Coli que presentó una sensibilidad a NTF de 100%. Al considerar la sensibilidad total (es decir de todos las bacterias uropatógenas Gram negativas, (BGN) la resistencia para NTF fue de 26%. Se debate además sus limitaciones médicas y algunos de los potenciales usos de NTF en pacientes hospitalizados

In the present investigation, sensitivity to nitrofurantoin (NTF) was determined through a retrospective observations analysis of reports of antibiograms, by diffusion disc, of urocultures from hospitalized gerontes. In the series observed (N=90), the most frequent development was E. coli, which showed a sensitivity to NTF of 100%. When considering the total sensitivity (ie of all Gram-negative uropathogenic bacteria, BGN) the resistance for NTF was 26%. It also discusses its medical limitations and some of the potential uses of NTF in hospitalized patients

Infecciones del tracto urinario, inmunidad y vacunación / Urinary tract infections, immunity, and vaccination

Resumen Las infecciones del tracto urinario (ITU) se consideran como una de las principales causas de morbilidad en el mundo, y Escherichia coli uropatogénica (UPEC, por sus siglas en inglés) es el agente causal asociado a estas infecciones. La alta morbilidad generada por las ITU y la limitación de tratamientos debido al aumento de la resistencia bacteriana a los diversos antibióticos inducen la búsqueda de nuevas alternativas contra estas infecciones. El conocimiento que se ha generado acerca de la respuesta inmunitaria en el tracto urinario (TU) es importante para el desarrollo de estrategias efectivas en la prevención, el tratamiento y el control de las ITU. Los avances en las herramientas de biología molecular y bioinformática han permitido generar proteínas de fusión consideradas como biomoléculas potenciales para el desarrollo de una vacuna viable contra las ITU. Las adhesinas fimbriales (FimH, CsgA y PapG) de UPEC son factores de virulencia que contribuyen a la adherencia, la invasión y la formación de comunidades bacterianas intracelulares. Pocos estudios in vivo e in vitro han mostrado que las proteínas de fusión promueven una respuesta inmunitaria eficiente y de protección contra las ITU causadas por UPEC. Adicionalmente, la vía de inmunización intranasal con moléculas inmunogénicas ha generado una respuesta en la mucosa del TU en comparación contra otras vías de inmunización. El objetivo de esta revisión fue proponer un diseño de vacuna contra las ITU causadas por UPEC, describiendo el panorama general de la infección, el mecanismo de patogenicidad de la bacteria y la respuesta inmunitaria del huésped.

Abstract Urinary tract infections (UTI) are considered one of the main causes of morbidity worldwide, and uropathogenic Escherichia coli (UPEC) is the etiological agent associated with these infections. The high morbidity produced by the UTI and the limitation of antibiotic treatments promotes the search for new alternatives against these infections. The knowledge that has been generated regarding the immune response in the urinary tract is important for the development of effective strategies in the UTI prevention, treatment, and control. Molecular biology and bioinformatic tools have allowed the construction of fusion proteins as biomolecules for the development of a viable vaccine against UTI. The fimbrial adhesins (FimH, CsgA, and PapG) of UPEC are virulence factors that contribute to the adhesion, invasion, and formation of intracellular bacterial communities. The generation of recombinant proteins from fimbrial adhesins as a single molecule is obtained by fusion technology. A few in vivo and in vitro studies have shown that fusion proteins provide an efficient immune response and protection against UTI produced by UPEC. Intranasal immunization of immunogenic molecules has generated a response in the urinary tract mucosa compared with other routes of immunization. The objective of this review was to propose a vaccine designed against UTI caused by UPEC, describing the general scenario of the infection, the mechanism of pathogenicity of bacteria, and the immune response of the host.

Recurrent Guillain-Barré Syndrome Following Urinary Tract Infection by Escherichia coli

Recurrent Guillain-Barré syndrome (GBS) is a rare, immune-mediated disease of the peripheral nervous system. It has been reported to occur at intervals ranging from four months to 10 years; published case studies suggest that 1%–6% of patients who have had GBS will experience recurrent attacks. The most commonly identified infections coinciding with GBS are Campylobacter jejuni, Haemophilus influenzae, Mycoplasma pneumonia, and cytomegalovirus, while an antecedent infection with Escherichia coli is very uncommon. In this case report, we present a rare episode of recurrent GBS, which followed a urinary tract infection (UTI) by E. coli, and an accompanying literature review. A 75-year-old woman with a prior history of acute motor axonal neuropathy (AMAN), a subtype of GBS, presented with subsequent weakness of limbs and areflexia following 10 days of fever, frequency, and dysuria. Base on nerve conduction studies, cerebrospinal fluid analysis and other clinical investigation, we diagnosed the patient with recurrent GBS caused by E. coli. The patient recovered with mild subjective weakness following treatment of intravenous immunoglobulin with ceftriaxone. We suggest that E. coli causes UTI could be one of the diverse trigger factors involved in recurrent GBS.

Relationships between Virulence Factors and Antimicrobial Resistance among Escherichia coli Isolated from Urinary Tract Infections and Commensal Isolates in Tehran, Iran

OBJECTIVES: Uropathogenic Escherichia coli (UPEC) are the major cause of urinary tract infections (UTIs). Here, we determined whether sensitivity to antibiotics was related to the prevalence of iron scavenging genes, or to biofilm and hemolysis formation. METHODS: A total of 110 UPEC and 30 E coli isolates were collected from the urine of UTI patients and feces of healthy individuals without UTI, respectively. The presence of iron receptor genes and phenotypic properties were evaluated by polymerase chain reaction and phenotypic methods, respectively. Susceptibility to routine antibiotics was evaluated using the disc diffusion method. RESULTS: The prevalence of iron scavenging genes ranged from 21.8% (ireA) to 84.5% (chuA) in the UPEC. Resistance to ceftazidime and cefotaxime was significantly correlated with the presence of fyuA and iutA iron genes. Biofilm production was significantly associated with the prevalence of fyuA and hma iron genes. A higher degree of antibiotic resistance was exhibited by isolates that produced biofilms than by their non-biofilm producing counterparts. CONCLUSION: Our study clearly indicates that biofilm production is associated with antibiotic resistance, and that iron receptors and hemolysin production also contribute to reduced antibiotic sensitivity. These results further our understanding of the role that these virulence factors play during UPEC pathogenesis, which in turn may be valuable for the development of novel treatment strategies against UTIs.

NDM-5 and OXA-48 Co-producing Uropathogenic Escherichia coli Isolate: First Case in Korea

No abstract available.

Prevalence of ambler class a extended-spectrum- ß -lactamases (ESBLS) among Uropathogenic Escherichia coli strains isolated from Rasht city, Iran / Prevalência de ambler extended-spectrum classe A- ß -lactamases (ESBLs) entre Uropathogenic Escherichia coli isolados da cidade de Rasht, Irã

Extended spectrum -lactamases (ESBLs), a group of bacterial enzymes which are the major cause of resistance to penicillins, broad spectrum cephalosporins and monobactams, are found among the member of Enterobacteriaceae. The class A ESBLs are mainly encoded by the plasmid mediated blaSHV, blaTEM and blaCTX-M genes. In this study, prevalence of Ambler class A ESBL genes among uropathogenic E. coli (UPEC) isolates associated with community acquired infections and their antibiotic susceptibility pattern was investigated. Seventy UPEC strains were isolated from urine samples and subjected to antimicrobial susceptibility assay using disk diffusion method. Phenotypic screening of ESBL production was evaluated according to the CLSI combined disk method. Genotyping of Ambler class A ESBLs was investigated using PCR. According to the results, ESBLs was identified in 37 isolates while molecular assay showed 47 isolates harbored ESBL genes. The most prevalence was recorded for blaTEM (74.2%) followed by blaCTX-M (43.2%) and blaSHV (12.2%). Imipenem was the most effective drug and ESBL producing isolates showed higher resistance to CAZ, CRO, CFZ, CTX and FOX compared to non ESBL isolates. In conclusion, high prevalence of class A ESBL genes was observed in our study which needs more consideration and rational antibiotic prescription.

As -lactamases de espectro alargado (ESBLs), um grupo de enzimas bacterianas que são a principal causa de resistência às penicilinas, cefalosporinas de largo espectro e monobactamas, encontram-se entre os membros das Enterobacteriaceae. As ESBLs de classe A são principalmente codificadas pelos genes blaSHV, blaTEM e blaCTX-M mediados por plasmídeo. Neste estudo, foi investigada a prevalência dos genes ESBL de classe A de Ambler entre isolados de E. coli uropatogênicos (UPEC) e seu padrão de suscetibilidade aos antibióticos. Setenta cepas UPEC foram isoladas a partir de amostras de urina e submetidas a ensaio de susceptibilidade antimicrobiana utilizando o método de difusão em disco. O rastreio fenotípico da produção de ESBL foi avaliado de acordo com o método de disco combinado CLSI. A genotipagem de ESBL de classe A de Ambler foi investigada usando PCR. De acordo com os resultados, as ESBLs foram identificadas em 37 isolados enquanto que o ensaio molecular mostrou 47 isolados portadores de genes ESBL. A maior prevalência foi registrada para blaTEM (74,2%), seguida de blaCTX-M (43,2%) e blaSHV (12,2%). O imipenem foi o fármaco mais eficaz e os isolados produtores de ESBL apresentaram maior resistência a CAZ, CRO, CFZ, CTX e FOX em comparação com os isolados não ESBL. Em conclusão, a alta prevalência de genes ESBL de classe A foi observada em nosso estudo, que necessita de maior atenção e prescrição de antibióticos racionais.

Prevalência de uropatógenos no laboratório de saúde pública de Macapá ­ AP entre 2009 e 2012 / Uropathogens prevalence in public health laboratory Macapá ­ AP between 2009 and 2012

Objetivo: Investigar a prevalência de uropatógenos de usuários atendidos no Laboratório Central de Saúde Pública de Macapá no período de 2009 a 2012. Métodos: Trata-se de um estudo retrospectivo de corte transversal, realizado no Laboratório Central de Saúde Públicade Macapá no período de 2009 a 2012, identificando os principais microrganismos responsáveis por infecções do trato urinário. O universo amostral foi composto pela população ambulatorial e hospitalar atendida no laboratório, sendo realizado o teste qui-quadrado. Os resultados foram expressos em números absolutos e em porcentagens utilizando-se o Programa Bioestat (5.0) e Excel Windows (2010). Resultados: Os resultados foram avaliados pela frequência das variáveis e analisados pelo teste qui-quadrado, destacando-se comocritérios: ocorrência, gênero, idade e o tipo de microrganismo causador e apresentados por meio de tabelas e gráficos. Das 10.026 (100%) uroculturas, observaram-se 7.758 (77,38%) com resultado negativo e 2.268 (22,62%) com resultado positivo. Os casos positivos foram separados em quatro grandes grupos: Enterobactérias ­ 1.422 (62,70%); Cocos Gram positivos ­ 663 (29,23%); Bacilo Gram negativo não fermentador ­102 (4,50%) e Fungo ­ 81 (3,57%). Os patógenos isolados mais prevalentes foram: Escherichia coli ­ 67,09%, Staphylococcus coagulase negativa ­ 20,8%, Acinetobacter baumanii ­ 38,23% e Candida albicans ­ 44,45%. Conclusão: O perfil epidemiológico de microrganismos e suas variáveis torna-se uma ferramenta imprescindível às investigações direcionadas à população susceptível. Tal conhecimento é relevante para a Saúde prestar maior assistência aos pacientes contribuindo para o planejamento, execução e avaliação das ações de prevenção, controle e tratamento

Objective: To investigate the prevalence of uropathogens of users served at the Central Laboratory of Public Health Macapá the period 2009 to 2012. Methods: This is a retrospective cross-sectional study, carried out at the Central Laboratory of Public Health Macapá the period 2009 to 2012, identifying key microorganisms responsible for urinary tract infections. The sample was composed of the Universe out patient population treated at the hospital and laboratory, which performed the chi-square test. Results were expressed in absolute numbers and in percentage using the Program Bioestat (5.0) and Windows Excel (2010). Results: The results were evaluated by variable frequency and analyzed by chi-square test, especially as criteria: occurrence, gender, age and type of causative microorganism and were presented descriptively and analytically through tables and graphs. Of 10.026 (100%) urine culture, there was 7.758 (77.38%) with negative and 2.268 (22.62%) with positive results. Positive cases were separated into four groups: Enterobacteria 1.422 (62.70%); Cocos Gram positive 663 (29.23%), Gram negative bacillus not fermentor 102 (4.50%) and Fungus 81 (3, 57%). The most prevalent pathogens isolated were Escherichia coli ­ 67.09%, 20.8% coagulase-negative Staphylococcus, Acinetobacter baumannii ­ 38.23% and 44.45% Candida albicans. Conclusion: The epidemiological profile of microorganisms and their variables becomes an indispensable tool for investigations directed at susceptible population. Such knowledge is relevant to health provide greater patient care by contributing to the planning, implementation and evaluation of prevention, control and treatment

Urocultivos en infección clínica de vías urinarias / RESULTS OF URINE CULTURE IN PATIENTS WITH CLINICAL URINARY TRACT INFECTION

Introducción: Las infecciones de vías urinarias (IVU) constituyen un problema de salud mundial. El aumento de la resistencia bacteriana a los antimicrobianos limita la administración de antibióticos económicos y de espectro limitado, lo que afecta el costo y el acceso a la atención. El objetivo de este trabajo es determinar la sensibilidad, resistencia y germen causal en urocultivos realizados en pacientes con infección clínica de vías urinarias. Métodos: Estudio transversal. Se analizaron urocultivos de pacientes con infección clínica de vías urinarias, cada urocultivo correspondió a un paciente. Las variables fueron edad, género, microorganismo causal, resistencia y sensibilidad a los antimicrobianos. Se realizó en la Unidad de Medicina Familiar No. 222 del Instituto Mexicano del Seguro Social en Toluca Estado de México. Se evaluaron urocultivos con más de 100000 Unidades formadoras de colonias. Se realizó mediciones descriptivas, frecuencias y porcentajes en el programa SPSS v. 17 para Windows. Resultados: se incluyeron urocultivos de pacientes con infección clínica de vías urinarias. La edad promedio de los pacientes fue de 50.09 ± 19.43 años, con predominio del género femenino (211 pacientes). Los agentes causales más frecuentes fueron: Escherichia Coli (51.91%), Proteus mirabilis (14.70%) y Staphylococcus (11.11 %). Los antibióticos con mayor sensibilidad fueron: imipenem, cefotetan y meropenem (34%). Los antimicrobianos con mayor resistencia fueron: ampicilina (24%), ciprofloxacino (22%) y ampicilina con sulbactam (20%). Conclusiones: los microorganismos más frecuentemente fueron: Escherichia coli y Proteus; y los antimicrobianos a los que mostraron más resistencia bacteriana fueron: ampicilina y quinolonas.

Introduction: Urinary tract infections (UTIs) are a global health problem. Increased bacterial resistance to antimicrobials limits the administration of low-spectrum antibiotics, which affect cost and access to care. The objective of this work is to determine the sensitivity, resistance and causal germ in urine cultures in patients with clinical urinary tract infection Methods: Transversal study. Urine cultures of patients with clinical urinary tract infection were analyzed, each urine culture corresponded to one patient. The variables were age, gender, causal microorganism, resistance and sensitivity to antimicrobials. It was performed at the Family Medicine Unit No. 222 of the Mexican Institute of Social Security in Toluca State of Mexico. Urocultures were evaluated with more than 100,000 colony forming units. Measurements were made frequencies and percentages in the SPSS program version 17 for Windows. Results: there were included 558 urine cultures; the average age was 50.09 ± 19.43 years, female predominance (211 patients). The most common causative microorganisms were Escherichia coli (51.91%), Proteus mirabilis (14.70%) and Staphylococcus (11.11%). Most sensitive antibiotics were: imipenem, meropenem and cefotetan (34%). Most resistance antimicrobial were: ampicillin (24%), ciprofloxacin (22%) and ampicillin with sulbactam (20%). Conclusions: Escherichia coli and Proteus were the most commonly isolated microorganisms; Ampicillin and quinolones showed more bacterial resistence.

Uropathogenic Escherichia coli ST131 in urinary tract infections in children / 소아과

PURPOSE: Escherichia coli sequence type (ST) 131, a multidrug-resistant clone causing extraintestinal infections, has rapidly become prevalent worldwide. However, the epidemiological and clinical features of pediatric infections are poorly understood. We aimed to explore the characteristics of ST131 Escherichia coli isolated from Korean children with urinary tract infections. METHODS: We examined 114 uropathogenic E. coli (UPEC) isolates from children hospitalized at Chung-Ang University Hospital between 2011 and 2014. Bacterial strains were classified into STs by partial sequencing of seven housekeeping genes (adk, fumC, gyrB, icd, mdh, purA, and recA). Clinical characteristics and antimicrobial susceptibility were compared between ST131 and non-ST131 UPEC isolates. RESULTS: Sixteen UPEC isolates (14.0%) were extended-spectrum β-lactamase (ESBL)-producers; 50.0% of ESBL-producers were ST131 isolates. Of all the isolates tested, 13.2% (15 of 114) were classified as ST131. There were no statistically significant associations between ST131 and age, sex, or clinical characteristics, including fever, white blood cell counts in urine and serum, C-reactive protein, radiologic abnormalities, and clinical outcome. However, ST131 isolates showed significantly lower rates of susceptibility to cefazolin (26.7%), cefotaxime (40.0%), cefepime (40.0%), and ciprofloxacin (53.3%) than non-ST131 isolates (65.7%, 91.9%, 92.9%, and 87.9%, respectively; P<0.001 for all). ESBL was more frequently produced in ST131 (53.3%) than in non-ST131 (8.1%) isolates (P<0.01). CONCLUSION: ST131 E. coli isolates were prevalent uropathogens in children at a single medical center in Korea between 2011 and 2014. Although ST131 isolates showed higher rates of antimicrobial resistance, clinical presentation and outcomes of patients were similar to those of patients infected with non-ST131 isolates.

Clonal and Virulence Distribution of Uropathogenic Escherichia coli Isolated from Children in Korea

Urinary tract infections (UTI) are one of the most frequent infectious diseases. Uropathogenic Escherichia coli (UPEC) are among major pathogens causing UTI. A variety of virulence genes are mainly responsible for the severity of these emerging infection. This study investigate the influences of virulence properties of UPEC isolates with reference to multi-locus sequence typing (MLST). The aim of this study was targeted that investigation of the bacterial pathogenicity associated with UTI in children. A total of 58 UPEC isolates were collected from urine samples from patients with clinical diagnosis of uncomplicated UTI. The MLST of UPEC strains were assessed by methods based on polymerase chain reaction. Motility was evaluated using soft-agar plates. Biofilm formation was analyzed in microtiter dish biofilm formation assay. Cell death assay was analyzed by Annexin V/Phosphatidylserine staining and DNA fragmentation assay. According the result, the predominant sequence type (ST) was ST95 (24.1%) and ST73 (17.2%). There were some difference in virulence gene and antibiotics resistance between ST95 and ST73. The number of 11 (18.9%) isolates were strongly adherent. Based on the detected biofilm formation, these strongly adherent are almost ST73. The ST95 was higher than ST73 in population, but ST95 was lower than ST73 in motility and cell death induction. This study indicated that the UPEC molecular strains are related to some virulence traits. Furthermore, the virulence factors carried by ST73 strains contribute to their abilities to colonize the host and cause disease.

Curli fimbria: an Escherichia coli adhesin associated with human cystitis

Abstract Escherichia coli is the major causative agent of human cystitis. In this study, a preliminary molecular analysis carried out by PCR (polymerase chain reaction) demonstrated that 100% of 31 E. coli strains isolated from patients with recurrent UTIs (urinary tract infections) showed the presence of the curli fimbria gene (csgA). Curli fimbria is known to be associated with bacterial biofilm formation but not with the adhesion of human cystitis-associated E. coli. Therefore, this work aimed to study how curli fimbria is associated with uropathogenic E. coli (UPEC) as an adhesion factor. For this purpose, the csgA gene was deleted from strain UPEC-4, which carries three adhesion factor genes (csgA, fimH and ompA). The wild-type UPEC-4 strain and its mutant (ΔcsgA) were analyzed for their adhesion ability over HTB-9 (human bladder carcinoma), Vero (kidney cells of African green monkey) and HUVEC (human umbilical vein) cells in the presence of α-D-mannose. All the wild-type UPEC strains tested (100%) were able to adhere to all three cell types, while the UPEC-4 ΔcsgA mutant lost its adherence to HTB-9 but continued to adhere to the HUVEC and Vero cells. The results suggest that curli fimbria has an important role in the adhesion processes associated with human UPEC-induced cystitis.