RESUMEN
The epidemiology of Clostridium difficile infections is highly dynamic as new strains continue to emerge worldwide. Here we present a detailed analysis of a new C. difficile strain (ICC-45) recovered from a cancer patient in Brazil that died from severe diarrhea. A polyphasic approach assigned a new PCR-ribotype and PFGE macrorestriction pattern to strain ICC-45, which is toxigenic (tcdA(+), tcdB(+) and ctdB(+)) and classified as ST41 from MLST Clade 2 and toxinotype IXb. Strain ICC-45 encodes for a variant TcdB that induces a distinct CPE in agreement with its toxinotype. Unlike epidemic NAP1/027 strains, which are also classified to MLST Clade 2, strain ICC-45 is susceptible to fluoroquinolones and does not overproduce toxins TcdA and TcdB. However, supernatants from strain ICC-45 and a NAP1/027 strain produced similar expression of pro-inflammatory cytokines, epithelial damage, and oxidative stress response in the mouse ileal loop model. These results highlight inflammation and oxidative stress as common features in the pathogenesis of C. difficile Clade 2 strains. Finally, this work contributes to the description of differences in virulence among various C. difficile strains.
Asunto(s)
Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Clostridioides difficile/aislamiento & purificación , Diarrea/diagnóstico , Enterocolitis Seudomembranosa/diagnóstico , Neoplasias/diagnóstico , Adulto , Animales , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/metabolismo , Clostridioides difficile/clasificación , Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/genética , Diarrea/complicaciones , Diarrea/microbiología , Modelos Animales de Enfermedad , Enterocolitis Seudomembranosa/complicaciones , Enterocolitis Seudomembranosa/tratamiento farmacológico , Enterocolitis Seudomembranosa/microbiología , Femenino , Expresión Génica , Humanos , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Masculino , Ratones , Tipificación de Secuencias Multilocus , Neoplasias/complicaciones , Neoplasias/microbiología , Estrés Oxidativo , Filogenia , Reacción en Cadena de la Polimerasa , RibotipificaciónRESUMEN
The objective of the present study was to investigate whether early undernutrition changes the chronic inflammatory response, so as to study its influence on pharmacological response to indomethacin. Rat offspring of dams fed from the first day of gestation to term or throughout the lactation period received a balanced diet (NN) or a basic regional diet (BRD) from northeast Brazil. According to their dams, the offspring were divided into three groups: NN; basic regional diet during gestation (BRD-g, undernourished during gestation); basic regional diet during gestation and lactation (BRD-gl, undernourished during gestation and lactation). At 2 months of age, Freund's adjuvant (0·2 ml) was inoculated into the plantar surface of the hind paw (day 0) of animals. All animals orally received saline (0·9 %) for 28 d. Another group of adult offspring was subjected to the same procedure as described above, but orally received indomethacin (2 mg/kg) instead of saline, and divided into three subgroups: NN treated with indomethacin (NNI); BRD-g treated with indomethacin (BRDI-g); BRD-gl treated with indomethacin (BRDI-gl). The hind paw volume was calculated on days 0 (initial paw volume), 7, 14 and 28. Hind paw swelling, blood albumin and C-reactive protein (CRP) levels and leucocyte counts were evaluated as markers of inflammation. Reduced hind paw swelling and the blood levels of serum albumin and CRP were found in the BRD-g and BRD-gl offspring. However, no difference was found in the leucocyte count. Compared with their respective saline-treated groups (NN, BRD-g and BRD-gl), the anti-inflammatory effect of indomethacin was lower in the BRDI-g and BRDI-gl groups than in the NNI group. We conclude that early undernutrition attenuated the chronic inflammatory response and the anti-inflammatory effect of indomethacin.