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1.
PLoS One ; 15(1): e0227425, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910229

RESUMO

Shigella species cause bacillary dysentery, especially among young individuals. Shigellae target the human colon for invasion; however, the initial adhesion mechanism is poorly understood. The Shigella surface protein IcsA, in addition to its role in actin-based motility, acts as a host cell adhesin through unknown mechanism(s). Here we confirmed the role of IcsA in cell adhesion and defined the region required for IcsA adhesin activity. Purified IcsA passenger domain was able block S. flexneri adherence and was also used as a molecular probe that recognised multiple components from host cells. The region within IcsA's functional passenger domain (aa 138-148) was identified by mutagenesis. Upon the deletion of this region, the purified IcsAΔ138-148 was found to no longer block S. flexneri adherence and had reduced ability to interact with host molecules. Furthermore, S. flexneri expressing IcsAΔ138-148 was found to be significantly defective in both cell adherence and invasion. Taken together, our data identify an adherence region within the IcsA functional domain and provides useful information for designing therapeutics for Shigella infection.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Disenteria Bacilar/genética , Interações entre Hospedeiro e Microrganismos/genética , Shigella flexneri/genética , Fatores de Transcrição/genética , Adesinas Bacterianas/genética , Adesão Celular/genética , Colo/microbiologia , Disenteria Bacilar/microbiologia , Humanos , Mutagênese , Mutação , Shigella flexneri/patogenicidade
2.
Biomed Res Int ; 2019: 6706230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828116

RESUMO

This study was undertaken to evaluate the activities of water/ethanol Cola anomala pods extract. In vitro antimicrobial susceptibility was determined by the disk diffusion method; the minimum inhibitory concentration and minimum bactericidal concentration were determined by agar dilution technique. In vivo, shigellosis was induced in healthy Wistar albino rats by oral administration of Shigella flexneri inoculum, 12 × 108 CFU/mL. At the onset of diarrhea, infected and normal control animals were subdivided into various groups treated with distilled water, with water/ethanol Cola anomala pods extract at 25, 50, or 100 mg/kg, or with ciprofloxacin, 2.5 mg/kg. After one-week treatment, rats were sacrificed, and blood and colon were collected. Blood was used for blood cell count. A portion of the colon served for histological studies while homogenate from the remaining part was centrifuged and the supernatant was collected for the determination of NO, PGE2, IL-1ß, and TNF-α levels. In vitro, water/ethanol Cola anomala pods extract showed to be bactericidal, with a minimum inhibitory concentration of 2.0 mg/mL and a minimum bactericidal concentration of 3.0 mg/mL. In diarrheic rats, the extract significantly (P < 0.01) increased the white blood cells and significantly (P < 0.01) decreased stool Shigella density from the first to the seventh day of treatment. It partially restored the structure of eroded intestine epithelium and prevented weight loss; the dose dependently and significantly (P < 0.001) decreased NO, IL-1ß, and TNF-α production in the colon and was found to have no significant effect on PGE2 production. These results support the use of this plant in traditional medicine in the treatment of gastrointestinal ailments.


Assuntos
Cola/química , Diarreia/tratamento farmacológico , Disenteria Bacilar/tratamento farmacológico , Shigella flexneri/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Ciprofloxacino/farmacologia , Colo/efeitos dos fármacos , Diarreia/genética , Diarreia/microbiologia , Modelos Animais de Doenças , Disenteria Bacilar/genética , Disenteria Bacilar/microbiologia , Fezes/microbiologia , Humanos , Interleucina-1beta/genética , Testes de Sensibilidade Microbiana , Óxido Nítrico/genética , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Shigella flexneri/patogenicidade , Fator de Necrose Tumoral alfa/genética
3.
BMJ Case Rep ; 12(12)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811109

RESUMO

We present a rare case of Shigella flexneri bacteraemia and the challenges of differentiating Escherichia coli and Shigella spp using conventional and newer laboratory techniques in diagnostic laboratories. The organism was identified only after whole genomic sequencing .


Assuntos
Bacteriemia/diagnóstico , Disenteria Bacilar/diagnóstico , Sequenciamento Completo do Genoma , Bacteriemia/microbiologia , Erros de Diagnóstico/prevenção & controle , Disenteria Bacilar/microbiologia , Escherichia coli/genética , Feminino , Humanos , Pessoa de Meia-Idade , Shigella flexneri/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sequenciamento Completo do Genoma/métodos
4.
BMC Infect Dis ; 19(1): 1037, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818261

RESUMO

BACKGROUND: Shigella spp. and entero-invasive E. coli (EIEC) use the same invasive mechanism to cause diarrheal diseases. Public health regulations apply only to Shigella spp. infections, but are hampered by the lack of simple methods to distinguish them from EIEC. In the last decades, molecular methods for detecting Shigella spp. and EIEC were implemented in medical microbiological laboratories (MMLs). However, shigellosis cases identified with molecular techniques alone are not notifiable in most countries. Our study investigates the impact of EIEC versus Shigella spp. infections and molecular diagnosed shigellosis versus culture confirmed shigellosis for re-examination of the rationale for the current public health regulations. METHODS: In this multicenter cross-sectional study, fecal samples of patients suspected for gastro-enteritis, referred to 15 MMLs in the Netherlands, were screened by PCR for Shigella spp. or EIEC. Samples were cultured to discriminate between the two pathogens. We compared risk factors, symptoms, severity of disease, secondary infections and socio-economic consequences for (i) culture-confirmed Shigella spp. versus culture-confirmed EIEC cases (ii) culture positive versus PCR positive only shigellosis cases. RESULTS: In 2016-2017, 777 PCR positive fecal samples with patient data were included, 254 of these were culture-confirmed shigellosis cases and 32 were culture-confirmed EIEC cases. EIEC cases were more likely to report ingestion of contaminated food and were less likely to be men who have sex with men (MSM). Both pathogens were shown to cause serious disease although differences in specific symptoms were observed. Culture-negative but PCR positive cases were more likely report travel or ingestion of contaminated food and were less likely to be MSM than culture-positive cases. Culture-negative cases were more likely to suffer from multiple symptoms. No differences in degree of secondary infections were observed between Shigella spp. and EIEC, and culture-negative and culture-positive cases. CONCLUSIONS: No convincing evidence was found to support the current guidelines that employs different measures based on species or detection method. Therefore, culture and molecular detection methods for Shigella spp. and EIEC should be considered equivalent for case definition and public health regulations regarding shigellosis. Differences were found regarding risks factors, indicating that different prevention strategies may be required.


Assuntos
Disenteria Bacilar/epidemiologia , Disenteria Bacilar/microbiologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Adolescente , Adulto , Técnicas Bacteriológicas/métodos , Estudos Transversais , Diarreia/microbiologia , Disenteria Bacilar/etiologia , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Infecções por Escherichia coli/etiologia , Fezes/microbiologia , Feminino , Gastroenterite/microbiologia , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Reação em Cadeia da Polimerase , Saúde Pública , Shigella/genética , Shigella/isolamento & purificação , Shigella/patogenicidade , Adulto Jovem
5.
Environ Health Prev Med ; 24(1): 82, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31883513

RESUMO

BACKGROUND: This study aimed to analyse the epidemiological characteristics of bacillary dysentery (BD) caused by Shigella in Chongqing, China, and to establish incidence prediction models based on the correlation between meteorological factors and BD, thus providing a scientific basis for the prevention and control of BD. METHODS: In this study, descriptive methods were employed to investigate the epidemiological distribution of BD. The Boruta algorithm was used to estimate the correlation between meteorological factors and BD incidence. The genetic algorithm (GA) combined with support vector regression (SVR) was used to establish the prediction models for BD incidence. RESULTS: In total, 68,855 cases of BD were included. The incidence declined from 36.312/100,000 to 23.613/100,000, with an obvious seasonal peak from May to October. Males were more predisposed to the infection than females (the ratio was 1.118:1). Children < 5 years old comprised the highest incidence (295.892/100,000) among all age categories, and pre-education children comprised the highest proportion (34,658 cases, 50.335%) among all occupational categories. Eight important meteorological factors, including the highest temperature, average temperature, average air pressure, precipitation and sunshine, were correlated with the monthly incidence of BD. The obtained mean absolute percent error (MAPE), mean squared error (MSE) and squared correlation coefficient (R2) of GA_SVR_MONTH values were 0.087, 0.101 and 0.922, respectively. CONCLUSION: From 2009 to 2016, BD incidence in Chongqing was still high, especially in the main urban areas and among the male and pre-education children populations. Eight meteorological factors, including temperature, air pressure, precipitation and sunshine, were the most important correlative feature sets of BD incidence. Moreover, BD incidence prediction models based on meteorological factors had better prediction accuracies. The findings in this study could provide a panorama of BD in Chongqing and offer a useful approach for predicting the incidence of infectious disease. Furthermore, this information could be used to improve current interventions and public health planning.


Assuntos
Disenteria Bacilar/epidemiologia , Shigella/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Disenteria Bacilar/microbiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Conceitos Meteorológicos , Pessoa de Meia-Idade , Modelos Teóricos , Adulto Jovem
6.
mBio ; 10(6)2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848280

RESUMO

Two Shigella species, Shigella flexneri and Shigella sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle- and high-income countries. S. flexneri is a prototypic cytosolic bacterium; once intracellular, it rapidly escapes the phagocytic vacuole and causes pyroptosis of macrophages, which is important for pathogenesis and bacterial spread. In contrast, little is known about the invasion, vacuole escape, and induction of pyroptosis during S. sonnei infection of macrophages. We demonstrate here that S. sonnei causes substantially less pyroptosis in human primary monocyte-derived macrophages and THP1 cells. This is due to reduced bacterial uptake and lower relative vacuole escape, which results in fewer cytosolic S. sonnei and hence reduced activation of caspase-1 inflammasomes. Mechanistically, the O-antigen (O-Ag), which in S. sonnei is contained in both the lipopolysaccharide and the capsule, was responsible for reduced uptake and the type 3 secretion system (T3SS) was required for vacuole escape. Our findings suggest that S. sonnei has adapted to an extracellular lifestyle by incorporating multiple layers of O-Ag onto its surface compared to other Shigella species.IMPORTANCE Diarrheal disease remains the second leading cause of death in children under five. Shigella remains a significant cause of diarrheal disease with two species, S. flexneri and S. sonnei, causing the majority of infections. S. flexneri are well known to cause cell death in macrophages, which contributes to the inflammatory nature of Shigella diarrhea. Here, we demonstrate that S. sonnei causes less cell death than S. flexneri due to a reduced number of bacteria present in the cell cytosol. We identify the O-Ag polysaccharide which, uniquely among Shigella spp., is present in two forms on the bacterial cell surface as the bacterial factor responsible. Our data indicate that S. sonnei differs from S. flexneri in key aspects of infection and that more attention should be given to characterization of S. sonnei infection.


Assuntos
Disenteria Bacilar/metabolismo , Disenteria Bacilar/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Inflamassomos/metabolismo , Antígenos O/imunologia , Shigella sonnei/fisiologia , Vacúolos/metabolismo , Endocitose/imunologia , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Modelos Biológicos , Piroptose/imunologia , Sistemas de Secreção Tipo III
7.
PLoS Pathog ; 15(11): e1007928, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31725799

RESUMO

Type 3 secretion systems (T3SSs) are conserved bacterial nanomachines that inject virulence proteins (effectors) into eukaryotic cells during infection. Due to their ability to inject heterologous proteins into human cells, these systems are being developed as therapeutic delivery devices. The T3SS assembles a translocon pore in the plasma membrane and then docks onto the pore. Docking activates effector secretion through the pore and into the host cytosol. Here, using Shigella flexneri, a model pathogen for the study of type 3 secretion, we determined the molecular mechanisms by which host intermediate filaments trigger docking and enable effector secretion. We show that the interaction of intermediate filaments with the translocon pore protein IpaC changed the pore's conformation in a manner that was required for docking. Intermediate filaments repositioned residues of the Shigella pore protein IpaC that are located on the surface of the pore and in the pore channel. Restricting these conformational changes blocked docking in an intermediate filament-dependent manner. These data demonstrate that a host-induced conformational change to the pore enables T3SS docking and effector secretion, providing new mechanistic insight into the regulation of type 3 secretion.


Assuntos
Antígenos de Bactérias/química , Antígenos de Bactérias/metabolismo , Membrana Celular/metabolismo , Disenteria Bacilar/metabolismo , Interações Hospedeiro-Patógeno , Shigella flexneri/metabolismo , Sistemas de Secreção Tipo III/metabolismo , Aderência Bacteriana , Disenteria Bacilar/microbiologia , Células HeLa , Humanos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Transporte Proteico , Shigella flexneri/patogenicidade , Sistemas de Secreção Tipo III/química , Virulência
8.
Nat Commun ; 10(1): 4828, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645551

RESUMO

Shigella sonnei increasingly dominates the international epidemiological landscape of shigellosis. Treatment options for S. sonnei are dwindling due to resistance to several key antimicrobials, including the fluoroquinolones. Here we analyse nearly 400 S. sonnei whole genome sequences from both endemic and non-endemic regions to delineate the evolutionary history of the recently emergent fluoroquinolone-resistant S. sonnei. We reaffirm that extant resistant organisms belong to a single clonal expansion event. Our results indicate that sequential accumulation of defining mutations (gyrA-S83L, parC-S80I, and gyrA-D87G) led to the emergence of the fluoroquinolone-resistant S. sonnei population around 2007 in South Asia. This clone was then transmitted globally, resulting in establishments in Southeast Asia and Europe. Mutation analysis suggests that the clone became dominant through enhanced adaptation to oxidative stress. Experimental evolution reveals that under fluoroquinolone exposure in vitro, resistant S. sonnei develops further intolerance to the antimicrobial while the susceptible counterpart fails to attain complete resistance.


Assuntos
Farmacorresistência Bacteriana/genética , Disenteria Bacilar/microbiologia , Fluoroquinolonas , Genoma Bacteriano/genética , Shigella sonnei/genética , Antibacterianos/uso terapêutico , Ásia Sudeste/epidemiologia , Ásia Ocidental/epidemiologia , Teorema de Bayes , Ciprofloxacino/uso terapêutico , DNA Girase/genética , DNA Topoisomerase IV/genética , Evolução Molecular Direcionada , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/epidemiologia , Europa (Continente)/epidemiologia , Evolução Molecular , Humanos , Epidemiologia Molecular , Mutação , Filogenia , Polimorfismo de Nucleotídeo Único , Shigella sonnei/fisiologia
9.
Pathog Dis ; 77(7)2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31578543

RESUMO

Shigella spp. are bacterial pathogens that invade the human colonic mucosa using a type III secretion apparatus (T3SA), a proteinaceous device activated upon contact with host cells. Active T3SAs translocate proteins that carve the intracellular niche of Shigella spp. Nevertheless, the activation state of the T3SA has not been addressed in vivo. Here, we used a green fluorescent protein transcription-based secretion activity reporter (TSAR) to provide a spatio-temporal description of S. flexneri T3SAs activity in the colon of Guinea pigs. First, we observed that early mucus release is triggered in the vicinity of luminal bacteria with inactive T3SA. Subsequent mucosal invasion showed bacteria with active T3SA associated with the brush border, eventually penetrating into epithelial cells. From 2 to 8 h post-challenge, the infection foci expanded, and these intracellular bacteria displayed homogeneously high-secreting activity, while extracellular foci within the lamina propria featured bacteria with low secretion activity. We also found evidence that within lamina propria macrophages, bacteria reside in vacuoles instead of accessing the cytosol. Finally, bacteria were cleared from tissues between 8 and 24 h post-challenge, highlighting the hit-and-run colonization strategy of Shigella. This study demonstrates how genetically encoded reporters can contribute to deciphering pathogenesis in vivo.


Assuntos
Colo/microbiologia , Disenteria Bacilar/microbiologia , Shigella flexneri/fisiologia , Sistemas de Secreção Tipo III/fisiologia , Animais , Biomarcadores , Modelos Animais de Doenças , Feminino , Genes Reporter , Cobaias , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Especificidade de Órgãos , Distribuição Tecidual
10.
Infect Immun ; 88(1)2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31611271

RESUMO

Human α-defensins are 3- to 5-kDa disulfide-bridged peptides with a multitude of antimicrobial activities and immunomodulatory functions. Recent studies show that human enteric α-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, aids the highly infectious enteropathogen Shigella in breaching the intestinal epithelium in vitro and in vivo Whether and how HD5 influences Shigella infection of resident macrophages following its invasion of the intestinal epithelium remain poorly understood. Here, we report that HD5 greatly promoted phagocytosis of Shigella by macrophages by targeting the bacteria to enhance bacterium-to-cell contacts in a structure- and sequence-dependent fashion. Subsequent intracellular multiplication of phagocytosed Shigella led to massive necrotic cell death and release of the bacteria. HD5-promoted phagocytosis of Shigella was independent of the status of the type 3 secretion system. Furthermore, HD5 neither inhibited nor enhanced phagosomal escape of Shigella Collectively, these findings confirm a potential pathogenic role of HD5 in Shigella infection of not only epithelial cells but also macrophages, illuminating how an enteropathogen exploits a host protective factor for virulence and infection.


Assuntos
Disenteria Bacilar/microbiologia , Disenteria Bacilar/patologia , Interações Hospedeiro-Patógeno , Shigella/patogenicidade , alfa-Defensinas/metabolismo , Animais , Aderência Bacteriana , Células Cultivadas , Células Epiteliais/microbiologia , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Macrófagos/microbiologia , Camundongos , Fagocitose
11.
Aust Vet J ; 97(11): 452-464, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31529470

RESUMO

BACKGROUND: Swine dysentery (SD) caused by Brachyspira hyodysenteriae is an important disease in Australia. AIM: The aim of this study is to evaluate the macrolide antibiotic kitasamycin for use in SD control. METHODS: The minimum inhibitory concentrations (MICs) of kitasamycin, tylosin and lincomycin for 32 Australian isolates of B. hyodysenteriae were evaluated. Mutations in the 23S rRNA gene were examined. Isolate '13' with a low kitasamycin MIC was used to challenge weaner pigs. Sixty pigs were housed in 20 pens each containing three pigs: pigs in four pens received 2 kg/tonne of a product containing kitasamycin (3.1% active) prophylactically in their food starting 4 days before B. hyodysenteriae challenge (group 1); pigs in four pens were challenged and received the same dose therapeutically once one pig in a pen showed diarrhoea (group 2); four pens were challenged and received 4 kg/tonne of the product therapeutically (group 3); four pens were challenged but not medicated (group 4); two pens were unmedicated and unchallenged (group 5) and two pens received 2 kg/tonne and were unchallenged (group 6). Pigs were monitored for B. hyodysenteriae excretion and disease. RESULTS: Macrolide resistance was widespread, and mutations in the 23S rRNA gene were identified in 23 isolates. Four isolates with kitasamycin MICs < 5 µg/mL were considered susceptible. Following experimental challenge, 10 of 12 unmedicated pigs developed SD. No pigs receiving kitasamycin prophylactical or therapeutically developed SD. Medicated pigs shed low numbers of B. hyodysenteriae in their faeces. CONCLUSIONS: Kitasamycin can help control SD in pigs infected with susceptible isolates of B. hyodysenteriae.


Assuntos
Antibacterianos/farmacologia , Brachyspira hyodysenteriae/efeitos dos fármacos , Disenteria Bacilar/veterinária , Infecções por Bactérias Gram-Negativas/veterinária , Kitasamicina/farmacologia , Doenças dos Suínos/tratamento farmacológico , Animais , Autopsia/veterinária , Modelos Animais de Doenças , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/microbiologia , Disenteria Bacilar/patologia , Genes de RNAr/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/patologia , Masculino , Testes de Sensibilidade Microbiana , Análise de Sequência de RNA , Suínos , Doenças dos Suínos/patologia , Austrália Ocidental
12.
Cell Host Microbe ; 26(3): 435-444.e4, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31492657

RESUMO

Intestinal epithelial cells are constantly exposed to pathogens and mechanical forces. However, the impact of mechanical forces on infections leading to diarrheal diseases remains largely unknown. Here, we addressed whether flow and peristalsis impact the infectivity of the human pathogen Shigella within a 3D colonic epithelium using Intestine-Chip technology. Strikingly, infection is significantly increased and minimal bacterial loads are sufficient to invade enterocytes from the apical side and trigger loss of barrier integrity, thereby shifting the paradigm about early stage Shigella invasion. Shigella quickly colonizes epithelial crypt-like invaginations and demonstrates the essential role of the microenvironment. Furthermore, by modulating the mechanical forces of the microenvironment, we find that peristalsis impacts Shigella invasion. Collectively, our results reveal that Shigella leverages the intestinal microenvironment by taking advantage of the microarchitecture and mechanical forces to efficiently invade the intestine. This approach will enable molecular and mechanistic interrogation of human-restricted enteric pathogens.


Assuntos
Disenteria Bacilar/microbiologia , Interações Hospedeiro-Patógeno , Intestinos/microbiologia , Aderência Bacteriana , Células CACO-2 , Enterócitos , Células Epiteliais/microbiologia , Humanos , Mucosa Intestinal/microbiologia , Shigella/patogenicidade
13.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(8): 988-991, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31484266

RESUMO

Objective: To investigate the etiologic and epidemiologic features of an infectious diarrhea outbreak in a boarding school in Fuyang city, Anhui province. Methods: Traceability hypothesis of this study was tested according to the epidemiological characteristics of the cases. Feces, anal swabs, water samples and food residues related to the patients and chefs were collected for pathogen isolation and detection. Biochemical identification, virulence gene detection, drug susceptibility test, PFGE and multilocus sequence typing were performed. Results: The incidence rate (3.41%) of different dormitory buildings within the water supply area by shallow wells was higher than that (0.98%) of the deep wells, with statistical significance (χ(2)=17.215, P<0.001). Sixteen strains belonged to the Shigella Sonneri family were isolated from the patient's samples, and all carrying the ipaH gene. Seven strains belonged to sen and ial genes. Set1 gene that did not appear in all the 16 strains were highly resistant to ampicillin, tetracycline, compound xinnomine, cefazoline, cefotaxime, gentamicin, naphthidinic acid and streptomycin, including 9 strains to doxycycline. The pulse field pattern of the 16 strains of Shigella sonneri appeared the same, with the ST type as ST152. Conclusion: When combined data from the etiological and epidemiological investigation, it was confirmed that Shigella sonneri was the pathogen of this outbreak, and water from the shallow wells might be responsible for the source of infection.


Assuntos
Surtos de Doenças , Disenteria Bacilar/diagnóstico , Disenteria Bacilar/epidemiologia , Fezes/microbiologia , Adolescente , Antibacterianos/uso terapêutico , China/epidemiologia , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/microbiologia , Feminino , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Shigella sonnei/efeitos dos fármacos , Shigella sonnei/isolamento & purificação
14.
Microb Drug Resist ; 25(10): 1465-1474, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31369341

RESUMO

Background: Emergence of multidrug-resistant Shigella, a major causative agent of bacterial dysentery, has generated many concerns not only in China but also worldwide. However, the prevalence of Shigella resistance caused by integron in the nonpopular season of diarrhea is not clear. Materials and Methods: Thirty-one Shigella flexneri and 22 Shigella sonnei samples collected in December 2010 from 10 cities of China were characterized for antimicrobial susceptibility, gene cassettes, widespread of integrons, and pulsed-field gel electrophoresis (PFGE) profile. Results: Multidrug resistance (MDR) was detected in 29 (93.5%) S. flexneri and 20 (90.9%) S. sonnei isolates. Class 1 integrons were detected in 25 (80.6%) S. flexneri and in 13 (59.1%) S. sonnei isolates; class 2 integrons were detected in 26 (83.9%) S. flexneri and in 19 (86.4%) S. sonnei isolates. Interestingly, the atypical class 1 integrons were mostly detected in S. flexneri (45.2%) isolates, whereas in only 1 (4.5%) S. sonnei isolate. DNA sequencing revealed two novel cassette arrays, dfrA5 and aacA4-cmlA, of class 1 integrons in S. flexneri, and dfrA17-aadA5 in S. sonnei isolates. The cassette arrays, dfrA1-sat1-aadA1 of class 2 integron and blaoxa-30-aadA1 of atypical class 1 integron, were also identified. PFGE profiles demonstrated A6 subtype of S. flexneri strains prevalent in Shanghai, Changchun, Jinan, and Changsha; and F6 subtype of S. sonnei prevalent in Jinan, Changchun, and Shanghai. Conclusion: The dissemination of MDR Shigella strains with integrons makes it an increasing public health problem in China. Increased surveillance and the development of adequate prevention strategies are warranted.


Assuntos
Antibacterianos/farmacologia , Disenteria Bacilar/epidemiologia , Integrons/genética , Shigella flexneri/efeitos dos fármacos , Shigella sonnei/efeitos dos fármacos , China/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Disenteria Bacilar/microbiologia , Eletroforese em Gel de Campo Pulsado , Humanos , Análise de Sequência de DNA , Shigella flexneri/genética , Shigella flexneri/isolamento & purificação , Shigella sonnei/genética , Shigella sonnei/isolamento & purificação
15.
Nat Microbiol ; 4(11): 2001-2009, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31383999

RESUMO

Pathogenic enterobacteria face various oxygen (O2) levels during intestinal colonization from the O2-deprived lumen to oxygenated tissues. Using Shigella flexneri as a model, we have previously demonstrated that epithelium invasion is promoted by O2 in a type III secretion system-dependent manner. However, subsequent pathogen adaptation to tissue oxygenation modulation remained unknown. Assessing single-cell distribution, together with tissue oxygenation, we demonstrate here that the colonic mucosa O2 is actively depleted by S. flexneri aerobic respiration-and not host neutrophils-during infection, leading to the formation of hypoxic foci of infection. This process is promoted by type III secretion system inactivation in infected tissues, favouring colonizers over explorers. We identify the molecular mechanisms supporting infectious hypoxia induction, and demonstrate here how enteropathogens optimize their colonization capacity in relation to their ability to manipulate tissue oxygenation during infection.


Assuntos
Disenteria Bacilar/metabolismo , Mucosa Intestinal/microbiologia , Oxigênio/metabolismo , Shigella flexneri/patogenicidade , Animais , Hipóxia Celular , Modelos Animais de Doenças , Disenteria Bacilar/microbiologia , Feminino , Cobaias , Células Hep G2 , Humanos , Mucosa Intestinal/metabolismo , Coelhos , Shigella flexneri/metabolismo , Sistemas de Secreção Tipo III/metabolismo
16.
Ann Clin Microbiol Antimicrob ; 18(1): 22, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288806

RESUMO

BACKGROUND: Shigella species are a major cause of dysentery and may attribute for death worldwide. Currently antibiotic resistance became the critical challenges for management of infectious disease. The aim was to conduct a systematic review and meta-analysis of Shigella species and its drug resistance pattern in Ethiopia. METHODS: A comprehensive literature search was conducted through internet searches using database of MEDLINE, PubMed, Google scholar, EMBASE, HINARI, Cochrane Library and reference lists of previous prevalence studies from January 1999 to November 2018. Results were presented in forest plot, tables and figures with 95% CI. The Cochrane Q test and I2 test statistic were used to test heterogeneity across studies. The Pooled estimate of Shigella species and its drug resistance pattern was computed by a random effects model. RESULTS: The pooled prevalence of Shigella species in Ethiopia was 6.6% (95% CI 4.7-8.8). In the subgroup analysis, the highest prevalence was observed among patients in Health facility (8.5%, 95% CI 6.2-11.5) whereas the lowest prevalence was observed in Community based studies (1.6%, 95% CI 0.8-3.4). In addition, Shigella species were highly resistant to ampicillin, amoxicillin, erythromycin and multi-drug resistant (MDR) with the pooled resistance proportions of 83.1% (95% CI 75.7-88.6), 84.1% (95% CI 75.6-90.1), 86.5% (95% CI 70.9-94.4) and 83.2% (95% CI 77.1-87.9), respectively. On the other hand, comparably low resistance pattern was reported for ciprofloxacin 8.9% (95% CI 6.0-12.8), ceftriaxone 9.3% (95% CI 3.9-20.5), and norfloxacin 8.2% (95% CI 3.8-16.6) and gentamycin 17.3% (95% CI 11.2-25.9). Subgroup analyses indicated that study years were associated with a decreasing Shigella prevalence over time (p = 0.002). CONCLUSION: The pooled estimate showed high burden of Shigella infection and its high proportion of drug resistance pattern to ampicillin, amoxicillin and erythromycin in Ethiopia. Therefore, initiating and scale up of performing drug susceptibility test for each shigellosis case, educate the community and health care providers on appropriate use of antibiotics need to be considered and strengthened.


Assuntos
Farmacorresistência Bacteriana , Disenteria Bacilar/epidemiologia , Disenteria Bacilar/microbiologia , Shigella/efeitos dos fármacos , Shigella/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Criança , Pré-Escolar , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
17.
Indian J Med Res ; 149(2): 247-256, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31219090

RESUMO

Background & objectives: Bacillary dysentery caused by Shigella spp. remains an important cause of the crisis in low-income countries. It has been observed that Shigella species have become increasingly resistant to most widely used antimicrobials. In this study, the antimicrobial resistance, virulence and plasmid profile of clinical isolates of Shigella species were determined. Methods: Sixty clinical Shigella isolates were subjected to whole-genome sequencing using Ion Torrent platform and the genome sequences were analyzed for the presence of acquired resistance genes, virulence genes and plasmids using web-based software tools. Results: Genome analysis revealed more resistance genes in Shigella flexneri than in other serogroups. Among ß-lactamases, blaOXA-1was predominantly seen followed by the blaTEM-1B and blaEC genes. For quinolone resistance, the qnr S gene was widely seen. Novel mutations in gyr B, par C and par E genes were observed. Cephalosporins resistance gene, blaCTX-M-15 was identified and plasmid-mediated AmpC ß-lactamases genes were found among the isolates. Further, a co-trimoxazole resistance gene was identified in most of the isolates studied. Virulence genes such as ipaD, ipaH, virF, senB, iha, capU, lpfA, sigA, pic, sepA, celb and gad were identified. Plasmid analysis revealed that the IncFII was the most commonly seen plasmid type in the isolates. Interpretation & conclusions: The presence of quinolone and cephalosporin resistance genes in Shigella serogroups has serious implications for the further spread of this resistance to other enteric pathogens or commensal organisms. This suggests the need for continuous surveillance to understand the epidemiology of the resistance.


Assuntos
Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Disenteria Bacilar/genética , Shigella/genética , beta-Lactamases/genética , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Cefalosporinas/efeitos adversos , Cefalosporinas/uso terapêutico , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/epidemiologia , Disenteria Bacilar/microbiologia , Fezes/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/efeitos dos fármacos , Plasmídeos/genética , Sorogrupo , Shigella/patogenicidade , Sequenciamento Completo do Genoma
19.
Pathog Glob Health ; 113(4): 173-179, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31221039

RESUMO

Shigella is the major cause of bacillary dysentery worldwide, especially in developing countries. There are several virulence factors essential for the organism to be virulent which are generally present in the virulence plasmid and on chromosomal pathogenicity islands. The present study was undertaken to determine the virulence gene profile of Shigella spp isolated from a clinical specimen and to study their significant association with common clinical symptoms and antimicrobial resistance. Sixty Shigella whole genome sequences, including 22 S. flexneri, 14 S. sonnei, 17 S. boydii and 7 S. dysenteriae were analyzed for the presence of virulence genes. The gene found predominantly in this study were ipaH (90%) followed by sigA (83%), and lpfA (78%) respectively. The virulence genes were significantly higher in S. flexneri, particularly in serotype 2 compared to S. sonnei. Interestingly, a significant association was observed between sigA gene and fever whereas sepA and sigA were found to be associated with diarrhea. Among the studied Shigella isolates, the presence of virulence genes was found higher in isolates resistant to more than three antibiotic classes. The present work revealed the varying incidence of virulence determinants among different Shigella serogroups and shows their contribution to disease severity.


Assuntos
Disenteria Bacilar/microbiologia , Disenteria Bacilar/patologia , Fezes/microbiologia , Genes Bacterianos , Genótipo , Shigella/genética , Fatores de Virulência/genética , Disenteria Bacilar/epidemiologia , Incidência , Índia/epidemiologia , Sorogrupo , Shigella/classificação , Shigella/isolamento & purificação , Shigella/patogenicidade
20.
Indian J Med Res ; 149(3): 412-417, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31249208

RESUMO

Background & objectives: : Shiga toxin (Stx) is produced by Shigella dysenteriae, a Gram-negative, facultative anaerobic bacillus that causes shigellosis, haemolytic uraemic syndrome (HUS) and Reiter's syndrome. The detection methods for shiga toxin needs to be rapid, accurate, reliable and must be extensively evaluated under field conditions. The aim of this study was to develop rapid, sensitive and specific detection method for Stx. Methods: : Mice and rabbits were immunized with purified recombinant Shiga toxin B (rStxB). Using these antibodies dot ELISA, sandwich ELISA and flow through assay were developed. Results: : The high-titre antibodies specifically reacted with purified rStxB. Dot-ELISA, sandwich ELISA and flow-through assay were developed and standardized that could detect StxB with limit of detection (LOD) of 9.75, 9.7 ng/ml and 0.46 µg/cassette, respectively. Interpretation & conclusions: : The rStxB was used to produce antibodies to avoid handling of pathogen. The Flow through assay 'developed was specific, rapid and field amenable.


Assuntos
Disenteria Bacilar/diagnóstico , Síndrome Hemolítico-Urêmica/diagnóstico , Toxina Shiga/isolamento & purificação , Shigella dysenteriae/genética , Animais , Anticorpos Antibacterianos/genética , Anticorpos Antibacterianos/imunologia , Artrite Reativa/diagnóstico , Artrite Reativa/genética , Artrite Reativa/microbiologia , Disenteria Bacilar/genética , Disenteria Bacilar/microbiologia , Ensaio de Imunoadsorção Enzimática , Escherichia coli/genética , Síndrome Hemolítico-Urêmica/genética , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Camundongos , Toxina Shiga/genética , Shigella dysenteriae/patogenicidade
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