RESUMO
Salmonella enterica serovar Typhimurium (STm) causes gastroenteritis and can progress to reactive arthritis (ReA). STm forms biofilms in the gut that secrete the amyloid curli, which we previously demonstrated can trigger autoimmunity in mice. HLA-B27 is a genetic risk factor for ReA; activation of the unfolded protein response (UPR) due to HLA-B27 misfolding is thought to play a critical role in ReA pathogenesis. To determine whether curli exacerbates HLA-B27-induced UPR, bone marrow-derived macrophages (BMDMs) isolated from HLA-B27 transgenic (tg) mice were used. BMDMs treated with purified curli exhibited elevated UPR compared to C57BL/6, and curli-induced IL-6 was reduced by pre-treating macrophages with inhibitors of the IRE1α branch of the UPR. In BMDMs, intracellular curli colocalized with GRP78, a regulator of the UPR. In vivo, acute infection with wild-type STm increased UPR markers in the ceca of HLA-B27tg mice compared to C57BL/6. STm biofilms that contain curli were visible in the lumen of cecal tissue sections. Furthermore, curli was associated with macrophages in the lamina propria, colocalizing with GRP78. Together, these results suggest that UPR plays a role in the curli-induced inflammatory response, especially in the presence of HLA-B27, a possible mechanistic link between STm infection and genetic susceptibility to ReA.
Assuntos
Proteínas de Bactérias , Chaperona BiP do Retículo Endoplasmático , Endorribonucleases , Antígeno HLA-B27 , Macrófagos , Proteínas Serina-Treonina Quinases , Salmonella typhimurium , Resposta a Proteínas não Dobradas , Animais , Humanos , Camundongos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Endorribonucleases/metabolismo , Endorribonucleases/genética , Antígeno HLA-B27/genética , Antígeno HLA-B27/metabolismo , Antígeno HLA-B27/imunologia , Interleucina-6/metabolismo , Interleucina-6/genética , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Infecções por Salmonella/imunologia , Infecções por Salmonella/microbiologia , Salmonella typhimurium/imunologiaRESUMO
BACKGROUND: Foodborne diseases (FBDs) represent a significant risk to public health, with nearly one in ten people falling ill every year globally. The large incidence of foodborne diseases in African low- and middle-income countries (LMIC) shows the immediate need for action, but there is still far to a robust and efficient outbreak detection system. The detection of outbreak heavily relies on clinical diagnosis, which are often delayed or ignored due to resource limitations and inadequate surveillance systems. METHODS: In total, 68 samples of non-typhoidal Salmonella isolates from human, animal and environmental sources collected between November 2021 and January 2023 were analyzed using sequencing methods to infer phylogenetic relationships between the samples. A source attribution model using a machine-learning logit-boost that predicted the likely source of infection for 20 cases of human salmonellosis was also run and compared with the results of the cluster detection. RESULTS: Three clusters of samples with close relation (SNP difference < 30) were identified as non-typhoidal Salmonella in Harar town and Kersa district, Ethiopia. These three clusters were comprised of isolates from different sources, including at least two human isolates. The isolates within each cluster showed identical serovar and sequence type (ST), with few exceptions in cluster 3. The close proximity of the samples suggested the occurrence of three potential outbreaks of non-typhoidal Salmonella in the region. The results of the source attribution model found that human cases of salmonellosis could primarily be attributed to bovine meat, which the results of the phylogenetic analysis corroborated. CONCLUSIONS: The findings of this study suggested the occurrence of three possible outbreaks of non-typhoidal Salmonella in eastern Ethiopia, emphasizing the importance of targeted intervention of food safety protocols in LMICs. It also highlighted the potential of integrated surveillance for detecting outbreak and identifying the most probable source. Source attribution models in combination with other epidemiological methods is recommended as part of a more robust and integrated surveillance system for foodborne diseases.
Assuntos
Surtos de Doenças , Doenças Transmitidas por Alimentos , Filogenia , Infecções por Salmonella , Salmonella , Humanos , Etiópia/epidemiologia , Salmonella/genética , Salmonella/isolamento & purificação , Salmonella/classificação , Doenças Transmitidas por Alimentos/microbiologia , Doenças Transmitidas por Alimentos/epidemiologia , Animais , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologiaRESUMO
Bacterial pathogens utilize the factors of their hosts to infect them, but which factors they exploit remain poorly defined. Here, we show that a pathogenic Salmonella enterica serovar Typhimurium (STm) exploits host polyamines for the functional expression of virulence factors. An STm mutant strain lacking principal genes required for polyamine synthesis and transport exhibited impaired infectivity in mice. A polyamine uptake-impaired strain of STm was unable to inject effectors of the type 3 secretion system into host cells due to a failure of needle assembly. STm infection stimulated host polyamine production by increasing arginase expression. The decline in polyamine levels caused by difluoromethylornithine, which inhibits host polyamine production, attenuated STm colonization, whereas polyamine supplementation augmented STm pathogenesis. Our work reveals that host polyamines are a key factor promoting STm infection, and therefore a promising therapeutic target for bacterial infection.
Assuntos
Poliaminas , Salmonella typhimurium , Sistemas de Secreção Tipo III , Fatores de Virulência , Salmonella typhimurium/metabolismo , Salmonella typhimurium/patogenicidade , Salmonella typhimurium/genética , Animais , Poliaminas/metabolismo , Camundongos , Sistemas de Secreção Tipo III/metabolismo , Sistemas de Secreção Tipo III/genética , Fatores de Virulência/metabolismo , Fatores de Virulência/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Interações Hospedeiro-Patógeno , Humanos , Infecções por Salmonella/metabolismo , Infecções por Salmonella/microbiologia , FemininoRESUMO
BACKGROUND: The increased resistance rate of Salmonella to third-generation cephalosporins represented by ceftriaxone (CRO) may result in the failure of the empirical use of third-generation cephalosporins for the treatment of Salmonella infection in children. The present study was conducted to evaluate a novel method for the rapid detection of CRO-resistant Salmonella (CRS). METHODS: We introduced the concept of the ratio of optical density (ROD) with and without CRO and combined it with matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) to establish a new protocol for the rapid detection of CRS. RESULTS: The optimal incubation time and CRO concentration determined by the model strain test were 2 h and 8 µg/ml, respectively. We then conducted confirmatory tests on 120 clinical strains. According to the receiver operating characteristic curve analysis, the ROD cutoff value for distinguishing CRS and non-CRS strains was 0.818 [area under the curve: 1.000; 95% confidence interval: 0.970-1.000; sensitivity: 100.00%; specificity: 100%; P < 10- 3]. CONCLUSIONS: In conclusion, the protocol for the combined ROD and MALDI-TOF MS represents a rapid, accurate, and economical method for the detection of CRS.
Assuntos
Antibacterianos , Ceftriaxona , Testes de Sensibilidade Microbiana , Infecções por Salmonella , Salmonella , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Ceftriaxona/farmacologia , Humanos , Antibacterianos/farmacologia , Salmonella/efeitos dos fármacos , Infecções por Salmonella/microbiologia , Testes de Sensibilidade Microbiana/métodos , Farmacorresistência Bacteriana , Sensibilidade e Especificidade , Curva ROCRESUMO
Understanding the dynamic evolution of Salmonella is vital for effective bacterial infection management. This study explores the role of the flexible genome, organised in regions of genomic plasticity (RGP), in shaping the pathogenicity of Salmonella lineages. Through comprehensive genomic analysis of 12,244 Salmonella spp. genomes covering 2 species, 6 subspecies, and 46 serovars, we uncover distinct integration patterns of pathogenicity-related gene clusters into RGP, challenging traditional views of gene distribution. These RGP exhibit distinct preferences for specific genomic spots, and the presence or absence of such spots across Salmonella lineages profoundly shapes strain pathogenicity. RGP preferences are guided by conserved flanking genes surrounding integration spots, implicating their involvement in regulatory networks and functional synergies with integrated gene clusters. Additionally, we emphasise the multifaceted contributions of plasmids and prophages to the pathogenicity of diverse Salmonella lineages. Overall, this study provides a comprehensive blueprint of the pathogenicity potential of Salmonella. This unique insight identifies genomic spots in nonpathogenic lineages that hold the potential for harbouring pathogenicity genes, providing a foundation for predicting future adaptations and developing targeted strategies against emerging human pathogenic strains.
Assuntos
Genoma Bacteriano , Salmonella , Salmonella/genética , Salmonella/patogenicidade , Genoma Bacteriano/genética , Virulência/genética , Humanos , Genômica/métodos , Família Multigênica , Filogenia , Plasmídeos/genética , Infecções por Salmonella/microbiologia , Prófagos/genética , Evolução MolecularRESUMO
Salmonella enterica serovar Newport is a human pathogen underreported in most developing countries. It is known for causing gastroenteritis and extraintestinal infections. In this case report, we report the case of ceftriaxone-resistant Salmonella enterica serovar Newport from South India, causing acute gastroenteritis in a sixty-year-old female patient having a history of antimicrobial therapy and recent hospital admission. Serovar Newport, especially among antibiotic-exposed patients, poses a significant public health threat due to its ability to acquire multidrug resistance. This emphasizes the necessity for robust surveillance and monitoring of nontyphoidal Salmonella infections, particularly given the limited data on serovar Newport in India. Vigilance in clinical practice and public health initiatives is crucial to effectively address the emergence and spread of multidrug-resistant strains.
Assuntos
Antibacterianos , Ceftriaxona , Infecções por Salmonella , Salmonella enterica , Humanos , Feminino , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Índia , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Farmacorresistência Bacteriana Múltipla , Gastroenterite/microbiologia , Gastroenterite/tratamento farmacológico , Sorogrupo , Testes de Sensibilidade MicrobianaRESUMO
Salmonella infections have been associated with cardiovascular complications, including myocarditis and myopericarditis. This presentation of Salmonella myopericarditis highlights key clinical features to aid in diagnosis and the importance of prompt treatment with antibiotics, colchicine and non-steroidal anti-inflammatory drugs (NSAIDs).
Assuntos
Antibacterianos , Anti-Inflamatórios não Esteroides , Dor no Peito , Colchicina , Miocardite , Pericardite , Infecções por Salmonella , Humanos , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/complicações , Infecções por Salmonella/microbiologia , Miocardite/microbiologia , Miocardite/tratamento farmacológico , Miocardite/diagnóstico , Dor no Peito/etiologia , Pericardite/microbiologia , Pericardite/tratamento farmacológico , Pericardite/diagnóstico , Antibacterianos/uso terapêutico , Colchicina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Masculino , Diagnóstico Diferencial , EletrocardiografiaRESUMO
Objective: Nontyphoidal Salmonella infection is one of the most common foodborne illnesses, and its oncogenic potential has been documented in animal models. The primary goal of this study was to examine whether individuals who were exposed to enteric Salmonella infection are more likely to develop colorectal cancer (CRC) than the general population through the linkage of 2 statewide public health surveillance databases. Materials and Methods: We designed a 2-stage probabilistic linkage, starting with 17,587 records of enteric salmonellosis reported to Michigan Department of Health and Human Services between 1992 and 2020. These records did not include unique identifiers (such as Social Security number [SSN]). The initial linkage to LexisNexis address history was conducted to obtain information to calculate each person's time in Michigan as well as SSN for the second linkage. The linkage to the state cancer registry was performed to obtain the observed number of CRC cases, while the expected number of CRC cases was calculated according to corresponding state CRC incidence by age, sex, and calendar year. Results: Ninety-three percent of the initially identified salmonellosis records were sent to LexisNexis linkage, which returned address history, death, and SSN for 97% of the records. Further linkage to the statewide cancer registry identified 98 incident CRC cases. Overall, the observed-to-expected (O/E) ratio was not different from unity (0.833; 95% CI, 0.627-1.003). Conclusions: While the new linkage strategy was found effective and should be applicable to other health conditions, we cannot rule out bias due to incomplete or underreporting of the infection in estimating the risk of CRC.
Assuntos
Neoplasias Colorretais , Sistema de Registros , Infecções por Salmonella , Humanos , Michigan/epidemiologia , Neoplasias Colorretais/epidemiologia , Incidência , Infecções por Salmonella/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Adulto Jovem , Adolescente , Registro Médico Coordenado , Idoso de 80 Anos ou maisRESUMO
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common foodborne enteric pathogen that infects humans or mammals and colonizes the intestinal tract primarily by invading the host following ingestion. Meanwhile, ClpV is a core secreted protein of the bacterial type VI secretion system (T6SS). Because elucidating ClpV's role in the pathogenesis of T6SS is pivotal for revealing the virulence mechanism of Salmonella, in our study, clpV gene deletion mutants were constructed using a λ-red-based recombination system, and the effect of clpV mutation on SL1344's pathogenicity was examined in terms of stress resistance, motility, cytokine secretion, gut microbiota, and a BALB/c mouse model. Among the results, ClpV affected SL1344's motility and was also involved in cell invasion, adhesion, and intracellular survival in the MDBK cell model but did not affect invasion or intracellular survival in the RAW264.7 cell model. Moreover, clpV gene deletion significantly reduced the transcription levels of GBP2b, IFNB1, IL-6, NLRP3, NOS2, and TNF-α proinflammatory factor levels but significantly increased transcription levels of IL-4 and IL-10 anti-inflammatory factors. Last, ClpV appeared to closely relate to the pathogenicity of S. Typhimurium in vivo, which can change the gut environment and cause dysbiosis of gut microbiota. Our findings elucidate the functions of ClpV in S. Typhimurium and illustrating interactions between T6SS and gut microbiota help to clarify the mechanisms of the pathogenesis of foodborne diseases.
Assuntos
Proteínas de Bactérias , Microbioma Gastrointestinal , Camundongos Endogâmicos BALB C , Salmonella typhimurium , Animais , Salmonella typhimurium/patogenicidade , Salmonella typhimurium/genética , Camundongos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Virulência , Humanos , Sistemas de Secreção Tipo VI/genética , Sistemas de Secreção Tipo VI/metabolismo , Feminino , Infecções por Salmonella/microbiologia , Infecções por Salmonella/imunologia , Células RAW 264.7RESUMO
In Salmonella enterica serovar Typhimurium (Typhimurium), multidrug resistance is associated with integrons carrying resistance genes dispersed by mobile genetic elements. This exploratory systematic review sought to identify integron types and their resistance genes in multidrug resistance Typhimurium isolates. We used Medline, PubMed, SciELO, ScienceDirect, Redalyc, and Google Scholar as motor searchers for articles in Spanish or English published between 2012 and 2020, including the keywords "integrons", "antibiotic resistance", and "Salmonella Typhimurium". We included 38 articles reporting multidrug resistance up to five antibiotic families. Class 1 integrons with aadA2 and blaPSE-1 gene cassettes were predominant, some probably related to the Salmonella genomic island 1. We did not find studies detailing class 1 and 2 integrons in the same isolate, nor class 3 integrons reported. The presence of integrons largely explains the resistance profiles found in isolates from different sources in 15 countries.
La multirresistencia a los antibióticos en Salmonella enterica serovar Typhimurium (Typhimurium) se asocia con integrones que portan genes de resistencia y que son dispersados por elementos genéticos móviles. En esta revisión sistemática exploratoria, se buscó identificar los tipos de integrones y sus genes de resistencia en aislamientos de Typhimurium multirresistentes a antibióticos. Se realizó una búsqueda de artículos en Medline, PubMed, SciELO, ScienceDirect, Redalyc y Google Académico, publicados entre el 2012 y el 2020, en español o inglés, con las palabras claves: "integrons", "antibiotic resistance" y "Salmonella Typhimurium". En el análisis se incluyeron 38 artículos que reportaron multirresistencia a cinco familias de antibióticos. Los integrones de clase 1 con casetes de genes aadA2 y blaPSE-1 fueron los predominantes, algunos probablemente relacionados con la isla genómica de Salmonella 1. No se encontraron integrones de clase 1 y 2 en un mismo aislamiento, ni se reportaron integrones de clase 3. La presencia de integrones explica en gran medida los perfiles de resistencia encontrados en aislamientos de diferentes fuentes de 15 países.
Assuntos
Farmacorresistência Bacteriana Múltipla , Integrons , Salmonella typhimurium , Integrons/genética , Farmacorresistência Bacteriana Múltipla/genética , Salmonella typhimurium/genética , Salmonella typhimurium/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Infecções por Salmonella/microbiologia , Infecções por Salmonella/epidemiologia , Ilhas Genômicas , AnimaisRESUMO
The emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages. Additionally, the in vivo safety and efficacy of the compounds were assessed using zebrafish embryo infection models. Our screen identified 11 hit compounds for Stm and 17 hit compounds for Mtb that were effective against intracellular bacteria and non-toxic for host cells. Further experiments were conducted to prioritize Stm hit compounds that were able to clear the intracellular infection in primary human macrophages. From these, two structurally related Stm hit compounds, GSK1379738A and GSK1379760A, exhibited significant activity against Stm in infected zebrafish embryos. In addition, we identified compounds that were active against intracellular Mtb, including morpholino-imidazo/triazolo-pyrimidinones that target PIK3CB, as well as 2-aminobenzimidazoles targeting ABL1. Overall, this study provided insights into kinase targets acting at the host-pathogen interface and identified several kinase inhibitors as potential HDTs.
Assuntos
Macrófagos , Mycobacterium tuberculosis , Inibidores de Proteínas Quinases , Salmonella typhimurium , Peixe-Zebra , Animais , Humanos , Salmonella typhimurium/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/enzimologia , Inibidores de Proteínas Quinases/farmacologia , Macrófagos/microbiologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Antibacterianos/farmacologia , Linhagem Celular , Embrião não Mamífero/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
Effective molecular strategies are needed to target pathogenic bacteria that thrive and proliferate within mammalian cells, a sanctuary inaccessible to many therapeutics. Herein, we present a class of cationic amphiphilic polyproline helices (CAPHs) with a rigid placement of the cationic moiety on the polyproline helix and assess the role of configuration of the unnatural proline residues making up the CAPHs. By shortening the distance between the guanidinium side chain and the proline backbone of the agents, a notable increase in cellular uptake and antibacterial activity was observed, whereas changing the configuration of the moieties on the pyrrolidine ring from cis to trans resulted in more modest increases. When the combination of these two activities was evaluated, the more rigid CAPHs were exceptionally effective at eradicating intracellular methicillin-resistant Staphylococcus aureus (MRSA) and Salmonella infections within macrophages, significantly exceeding the clearance with the parent CAPH.
Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Peptídeos , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Peptídeos/química , Peptídeos/farmacologia , Macrófagos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Cátions/química , Cátions/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Humanos , Infecções por Salmonella/microbiologia , Infecções por Salmonella/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologiaRESUMO
The bacterial species Salmonella enterica (S. enterica) is a highly diverse pathogen containing more than 2600 distinct serovars, which can infect a wide range of animal and human hosts. Recent global emergence of multidrug resistant strains, from serovars Infantis and Muenchen is associated with acquisition of the epidemic megaplasmid, pESI that augments antimicrobial resistance and pathogenicity. One of the main pESI's virulence factors is the potent iron uptake system, yersiniabactin encoded by fyuA, irp2-irp1-ybtUTE, ybtA, and ybtPQXS gene cluster. Here we show that yersiniabactin, has an underappreciated distribution among different S. enterica serovars and subspecies, integrated in their chromosome or carried by different conjugative plasmids, including pESI. While the genetic organization and the coding sequence of the yersiniabactin genes are generally conserved, a 201-bp insertion sequence upstream to ybtA, was identified in pESI. Despite this insertion, pESI-encoded yersiniabactin is regulated by YbtA and the ancestral Ferric Uptake Regulator (Fur), which binds directly to the ybtA and irp2 promoters. Furthermore, we show that yersiniabactin genes are specifically induced during the mid-late logarithmic growth phase and in response to iron-starvation or hydrogen peroxide. Concurring, yersiniabactin was found to play a previously unknown role in oxidative stress tolerance and to enhance intestinal colonization of S. Infantis in mice. These results indicate that yersiniabactin contributes to Salmonella fitness and pathogenicity in vivo and is likely to play a role in the rapid dissemination of pESI among globally emerging Salmonella lineages.
Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Ferro , Estresse Oxidativo , Salmonella enterica , Animais , Ferro/metabolismo , Camundongos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Salmonella enterica/genética , Salmonella enterica/metabolismo , Salmonella enterica/patogenicidade , Virulência/genética , Fenóis/metabolismo , Tiazóis/metabolismo , Humanos , Infecções por Salmonella/microbiologia , Transferência Genética Horizontal , Feminino , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Plasmídeos/genéticaAssuntos
Infecções por Salmonella , Esplenopatias , Humanos , Esplenopatias/microbiologia , Esplenopatias/diagnóstico por imagem , Infecções por Salmonella/microbiologia , Masculino , Criança , Abscesso/microbiologia , Abscesso/diagnóstico por imagem , Feminino , Abscesso Abdominal/microbiologia , Abscesso Abdominal/diagnóstico por imagemRESUMO
Salmonella is a foodborne pathogen that causes disruption of intestinal mucosal immunity, leading to acute gastroenteritis in the host. In this study, we found that Salmonella Typhimurium (STM) infection of the intestinal tract of mice led to a significant increase in the proportion of Lacticaseibacillus, while the secretion of IL-22 from type 3 innate lymphoid cells (ILC3) increased significantly. Feeding Lacticaseibacillus rhamnosus GG (LGG) effectively alleviated the infection of STM in the mouse intestines. TLR2-/- mice experiments found that TLR2-expressing dendritic cells (DCs) are crucial for LGG's activation of ILC3. Subsequent in vitro experiments showed that heat-killed LGG (HK-LGG) could promote DCs to secrete IL-23, which in turn further promotes the activation of ILC3 and the secretion of IL-22. Finally, organoid experiments further verified that IL-22 secreted by ILC3 can enhance the intestinal mucosal immune barrier and inhibit STM infection. This study demonstrates that oral administration of LGG is a potential method for inhibiting STM infection.
Assuntos
Interleucina 22 , Interleucinas , Lacticaseibacillus rhamnosus , Linfócitos , Infecções por Salmonella , Salmonella typhimurium , Receptor 2 Toll-Like , Animais , Camundongos , Salmonella typhimurium/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Linfócitos/imunologia , Lacticaseibacillus rhamnosus/imunologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/microbiologia , Interleucinas/imunologia , Interleucinas/metabolismo , Camundongos Knockout , Camundongos Endogâmicos C57BL , Células Dendríticas/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Imunidade Inata , Probióticos/administração & dosagem , Imunidade nas MucosasRESUMO
In order to survive and replicate, Salmonella has evolved mechanisms to gain access to intestinal epithelial cells of the crypt. However, the impact of Salmonella Typhimurium on stem cells and progenitors, which are responsible for the ability of the intestinal epithelium to renew and protect itself, remains unclear. Given that intestinal organoids growth is sustained by stem cells and progenitors activity, we have used this model to document the effects of Salmonella Typhimurium infection on epithelial proliferation and differentiation, and compared it to an in vivo model of Salmonella infection in mice. Among gut segments, the caecum was preferentially targeted by Salmonella. Analysis of infected crypts and organoids demonstrated increased length and size, respectively. mRNA transcription profiles of infected crypts and organoids pointed to upregulated EGFR-dependent signals, associated with a decrease in secretory cell lineage differentiation. To conclude, we show that organoids are suited to mimic the impact of Salmonella on stem cells and progenitors cells, carrying a great potential to drastically reduce the use of animals for scientific studies on that topic. In both models, the EGFR pathway, crucial to stem cells and progenitors proliferation and differentiation, is dysregulated by Salmonella, suggesting that repeated infections might have consequences on crypt integrity and further oncogenesis.
Assuntos
Diferenciação Celular , Receptores ErbB , Organoides , Infecções por Salmonella , Salmonella typhimurium , Células-Tronco , Animais , Organoides/microbiologia , Células-Tronco/metabolismo , Camundongos , Salmonella typhimurium/patogenicidade , Salmonella typhimurium/fisiologia , Infecções por Salmonella/microbiologia , Infecções por Salmonella/patologia , Receptores ErbB/metabolismo , Receptores ErbB/genética , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Proliferação de Células , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Abdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications. CASE PRESENTATION: A 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up. CONCLUSIONS: This case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula.
Assuntos
Sepse , Humanos , Masculino , Pessoa de Meia-Idade , Sepse/microbiologia , Sepse/complicações , Aorta Abdominal/cirurgia , Aorta Abdominal/microbiologia , Enterococcus faecium/isolamento & purificação , Antibacterianos/uso terapêutico , Streptococcus anginosus/isolamento & purificação , Fístula Intestinal/microbiologia , Fístula Intestinal/cirurgia , Fístula Intestinal/complicações , Salmonella/isolamento & purificação , Escherichia coli/isolamento & purificação , Recidiva , Duodenopatias/microbiologia , Duodenopatias/cirurgia , Duodenopatias/complicações , Infecções por Salmonella/microbiologia , Infecções por Salmonella/complicações , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/tratamento farmacológicoRESUMO
RATIONALE: Bacterascites are a rare complication of cesarean sections (C/S). Here, we report the case of a patient with bacterascites after an emergent C/S. PATIENT CONCERN: A 41-year-old female reported diffuse abdominal tightness and pain for a week after C/S, who received C/S at 38 4/7 weeks due to superimposed preeclampsia and prolonged labor. DIAGNOSES: Bacterascites caused by Salmonella species after C/S was diagnosed. INTERVENTIONS: Initial treatment included cefmetazole and metronidazole. On day 2, paracentesis was performed, followed by albumin and hydroxyethyl starch administration. By day 3, the patient developed pulmonary edema, necessitating Lasix administration. On day 6, ascites culture revealed Salmonella species resistant to third-generation cephalosporins, leading to meropenem therapy adjustment. This resulted in improved symptoms. Meropenem was continued for 14 days to complete the treatment regimen. OUTCOMES: Follow-up ultrasonography revealed a decrease in ascites. As the patient clinical condition improved, she was discharged on day 20 and scheduled for outpatient department follow-up. No recurrence of ascites was observed during the subsequent follow-up period of 3 months. No ascites were noted 8 days after discharge. LESSONS: Postoperative bacterascites with Salmonella were diagnosed. Antibiotic treatment and therapeutic paracentesis were effective for this condition.
Assuntos
Antibacterianos , Cesárea , Infecções por Salmonella , Salmonella , Humanos , Feminino , Adulto , Cesárea/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Salmonella/isolamento & purificação , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/tratamento farmacológico , Gravidez , Meropeném/uso terapêutico , Meropeném/administração & dosagem , Ascite/etiologia , Ascite/microbiologia , Bacteriemia/microbiologia , Bacteriemia/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Paracentese/métodosRESUMO
The vast dissemination of resistance to different antibiotics among bacterial pathogens, especially foodborne pathogens, has drawn major research attention. Thus, many attempts have been made to reveal novel alternatives to the current antibiotics. Due to their variable pharmacologically active phytochemicals, plants represent a good solution for this issue. This study investigated the antibacterial potential of Kumquat or Fortunella japonica methanol extract (FJME) against Salmonella typhimurium clinical isolates. Gas chromatography coupled with mass spectrometry (GC/MS) characterized 39 compounds in FJME. Palmitic acid (15.386%) and cis-vaccenic acid (15.012%) are the major active constituents detected by GC/MS. Remarkably, FJME had minimum inhibitory concentrations from 128 to 512 µg/mL in vitro. In addition, a systemic infection model revealed the in vivo antibacterial action of FJME. The antibacterial therapeutic activity of FJME was noticed by improving the histological features of the liver and spleen. Moreover, there was a perceptible lessening (p < 0.05) of the levels of the oxidative stress markers (nitric oxide and malondialdehyde) using ELISA. In addition, the gene expression of the proinflammatory cytokine (interleukin 6) was downregulated. On the other hand, there was an upregulation of the anti-inflammatory cytokine (interleukin 10). Accordingly, future clinical investigations should be done to reveal the potential antibacterial action of FJME on other food pathogens.
Assuntos
Antibacterianos , Frutas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Salmonella typhimurium , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Salmonella typhimurium/efeitos dos fármacos , Antibacterianos/farmacologia , Frutas/microbiologia , Frutas/química , Animais , Camundongos , Infecções por Salmonella/microbiologia , Infecções por Salmonella/tratamento farmacológicoRESUMO
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (-44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.