RESUMO
Nontyphoidal Salmonella (NTS), particularly Salmonella enterica serovar Typhimurium, is among the leading etiologic agents of bacterial enterocolitis globally and a well-characterized cause of invasive disease (iNTS) in sub-Saharan Africa. In contrast, S Typhimurium is poorly defined in Southeast Asia, a known hot spot for zoonotic disease with a recently described burden of iNTS disease. Here, we aimed to add insight into the epidemiology and potential impact of zoonotic transfer and antimicrobial resistance (AMR) in S Typhimurium associated with iNTS and enterocolitis in Vietnam. We performed whole-genome sequencing and phylogenetic reconstruction on 85 human (enterocolitis, carriage, and iNTS) and 113 animal S Typhimurium isolates isolated in Vietnam. We found limited evidence for the zoonotic transmission of S Typhimurium. However, we describe a chain of events where a pandemic monophasic variant of S Typhimurium (serovar I:4,[5],12:i:- sequence type 34 [ST34]) has been introduced into Vietnam, reacquired a phase 2 flagellum, and acquired an IncHI2 multidrug-resistant plasmid. Notably, these novel biphasic ST34 S Typhimurium variants were significantly associated with iNTS in Vietnamese HIV-infected patients. Our study represents the first characterization of novel iNTS organisms isolated outside sub-Saharan Africa and outlines a new pathway for the emergence of alternative Salmonella variants into susceptible human populations.IMPORTANCESalmonella Typhimurium is a major diarrheal pathogen and associated with invasive nontyphoid Salmonella (iNTS) disease in vulnerable populations. We present the first characterization of iNTS organisms in Southeast Asia and describe a different evolutionary trajectory from that of organisms causing iNTS in sub-Saharan Africa. In Vietnam, the globally distributed monophasic variant of Salmonella Typhimurium, the serovar I:4,[5],12:i:- ST34 clone, has reacquired a phase 2 flagellum and gained a multidrug-resistant plasmid to become associated with iNTS disease in HIV-infected patients. We document distinct communities of S Typhimurium and I:4,[5],12:i:- in animals and humans in Vietnam, despite the greater mixing of these host populations here. These data highlight the importance of whole-genome sequencing surveillance in a One Health context in understanding the evolution and spread of resistant bacterial infections.
Assuntos
Farmacorresistência Bacteriana Múltipla , Salmonelose Animal/epidemiologia , Salmonelose Animal/microbiologia , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Salmonella typhimurium/classificação , Salmonella typhimurium/efeitos dos fármacos , Animais , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Galinhas , Transmissão de Doença Infecciosa , Patos , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Variação Genética , Genótipo , Infecções por HIV/complicações , Humanos , Hospedeiro Imunocomprometido , Epidemiologia Molecular , Infecções por Salmonella/transmissão , Salmonelose Animal/transmissão , Salmonella typhimurium/genética , Salmonella typhimurium/isolamento & purificação , Suínos , Vietnã/epidemiologia , Sequenciamento Completo do Genoma , Zoonoses/epidemiologia , Zoonoses/microbiologia , Zoonoses/transmissãoRESUMO
BACKGROUND: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. METHODS: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. RESULTS: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. CONCLUSIONS: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid.
RESUMO
Fluoroquinolones came into widespread use in African countries in the early 2000s, after patents for the first generation of these drugs expired. By that time, quinolone antibacterial agents had been used intensively worldwide and resistant lineages of many bacterial species had evolved. We sought to understand which Gram negative enteric pandemic lineages have been reported from Africa, as well as the nature and transmission of any indigenous resistant clones. A systematic review of articles indexed in the Medline and AJOL literature databases was conducted. We report on the findings of 43 eligible studies documenting local or pandemic fluoroquinolone-resistant enteric clones in sub-Sahara African countries. Most reports are of invasive non-typhoidal Salmonella and Escherichia coli lineages and there have been three reports of cholera outbreaks caused by fluoroquinolone-resistant Vibrio cholerae O1. Fluoroquinolone-resistant clones have also been reported from commensals and animal isolates but there are few data for non-Enterobacteriaceae and almost none for difficult-to-culture Campylobacter spp. Fluoroquinolone-resistant lineages identified in African countries were universally resistant to multiple other classes of antibacterial agents. Although as many as 972 non-duplicate articles refer to fluoroquinolone resistance in enteric bacteria from Africa, most do not report on subtypes and therefore information on the epidemiology of fluoroquinolone-resistant clones is available from only a handful of countries in the subcontinent. When resistance is reported, resistance mechanisms and lineage information is rarely investigated. Insufficient attention has been given to molecular and sequence-based methods necessary for identifying and tracking resistant clones in Africa and more research is needed in this area.
RESUMO
Salmonella enterica serovar Weltevreden (S. Weltevreden) is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions. Despite the regional and international emergence of this Salmonella serovar, relatively little is known about its genetic diversity, genomics or virulence potential in model systems. Here we used whole genome sequencing and bioinformatics analyses to define the phylogenetic structure of a diverse global selection of S. Weltevreden. Phylogenetic analysis of more than 100 isolates demonstrated that the population of S. Weltevreden can be segregated into two main phylogenetic clusters, one associated predominantly with continental Southeast Asia and the other more internationally dispersed. Subcluster analysis suggested the local evolution of S. Weltevreden within specific geographical regions. Four of the isolates were sequenced using long read sequencing to produce high quality reference genomes. Phenotypic analysis in Hep-2 cells and in a murine infection model indicated that S. Weltevreden were significantly attenuated in these models compared to the classical S. Typhimurium reference strain SL1344. Our work outlines novel insights into this important emerging pathogen and provides a baseline understanding for future research studies.
Assuntos
Diarreia/microbiologia , Filogenia , Infecções por Salmonella/microbiologia , Salmonella enterica/classificação , Salmonella enterica/isolamento & purificação , Animais , Sudeste Asiático/epidemiologia , Proteínas de Bactérias/genética , Diarreia/epidemiologia , Variação Genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Fenótipo , Infecções por Salmonella/epidemiologia , Salmonella enterica/genéticaRESUMO
The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.
Assuntos
Salmonella typhi/genética , Febre Tifoide/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Genoma Bacteriano , Humanos , Dados de Sequência Molecular , Filogenia , Filogeografia , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Análise de Sequência de DNA , Febre Tifoide/tratamento farmacológico , Febre Tifoide/transmissãoRESUMO
BACKGROUND: Nontyphoidal Salmonellae (NTS) cause a large burden of invasive and gastrointestinal disease among young children in sub-Saharan Africa. No vaccine is currently available. Previous reports indicate the importance of the O-antigen of Salmonella lipopolysaccharide for virulence and resistance to antibody-mediated killing. We hypothesised that isolates with more O-antigen have increased resistance to antibody-mediated killing and are more likely to be invasive than gastrointestinal. METHODOLOGY/PRINCIPAL FINDINGS: We studied 192 NTS isolates (114 Typhimurium, 78 Enteritidis) from blood and stools, mostly from paediatric admissions in Kenya 2000-2011. Isolates were tested for susceptibility to antibody-mediated killing, using whole adult serum. O-antigen structural characteristics, including O-acetylation and glucosylation, were investigated. Overall, isolates were susceptible to antibody-mediated killing, but S. Enteritidis were less susceptible and expressed more O-antigen than Typhimurium (p<0.0001 for both comparisons). For S. Typhimurium, but not Enteritidis, O-antigen expression correlated with reduced sensitivity to killing (r = 0.29, 95% CI = 0.10-0.45, p = 0.002). Both serovars expressed O-antigen populations ranging 21-33 kDa average molecular weight. O-antigen from most Typhimurium were O-acetylated on rhamnose and abequose residues, while Enteritidis O-antigen had low or no O-acetylation. Both Typhimurium and Enteritidis O-antigen were approximately 20%-50% glucosylated. Amount of S. Typhimurium O-antigen and O-antigen glucosylation level were inversely related. There was no clear association between clinical presentation and antibody susceptibility, O-antigen level or other O-antigen features. CONCLUSION/SIGNIFICANCE: Kenyan S. Typhimurium and Enteritidis clinical isolates are susceptible to antibody-mediated killing, with degree of susceptibility varying with level of O-antigen for S. Typhimurium. This supports the development of an antibody-inducing vaccine against NTS for Africa. No clear differences were found in the phenotype of isolates from blood and stool, suggesting that the same isolates can cause invasive disease and gastroenteritis. Genome studies are required to understand whether invasive and gastrointestinal isolates differ at the genotypic level.
Assuntos
Anticorpos Antibacterianos/imunologia , Trato Gastrointestinal/microbiologia , Antígenos O/imunologia , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/imunologia , Salmonella enteritidis/imunologia , Salmonella typhimurium/imunologia , Acetilação , Anticorpos Antibacterianos/sangue , Criança , Fezes/microbiologia , Glicosilação , Humanos , Quênia/epidemiologia , Antígenos O/metabolismo , Infecções por Salmonella/sangue , Salmonella enteritidis/genética , Salmonella typhimurium/genética , Especificidade da EspécieRESUMO
Multidrug-resistant bacteria pose a major challenge to the clinical management of infections in resource-poor settings. Although nontyphoidal Salmonella (NTS) bacteria cause predominantly enteric self-limiting illness in developed countries, NTS is responsible for a huge burden of life-threatening bloodstream infections in sub-Saharan Africa. Here, we characterized nine S. Typhimurium isolates from an outbreak involving patients who initially failed to respond to ceftriaxone treatment at a referral hospital in Kenya. These Salmonella enterica serotype Typhimurium isolates were resistant to ampicillin, chloramphenicol, cefuroxime, ceftriaxone, aztreonam, cefepime, sulfamethoxazole-trimethoprim, and cefpodoxime. Resistance to ß-lactams, including to ceftriaxone, was associated with carriage of a combination of blaCTX-M-15, blaOXA-1, and blaTEM-1 genes. The genes encoding resistance to heavy-metal ions were borne on the novel IncHI2 plasmid pKST313, which also carried a pair of class 1 integrons. All nine isolates formed a single clade within S. Typhimurium ST313, the major clone of an ongoing invasive NTS epidemic in the region. This emerging ceftriaxone-resistant clone may pose a major challenge in the management of invasive NTS in sub-Saharan Africa.
Assuntos
Antibacterianos/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Ampicilina/farmacologia , Proteínas de Bactérias/genética , Ceftriaxona , Cefuroxima/farmacologia , Cloranfenicol/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Quênia , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Salmonella typhimurium/genética , SorogrupoRESUMO
Salmonella is an enteric pathogen that causes a range of diseases in humans. Non-typhoidal Salmonella (NTS) serovars such as Salmonella enterica serovar Typhimurium generally cause a self-limiting gastroenteritis whereas typhoidal serovars cause a systemic disease, typhoid fever. However, S. Typhimurium isolates within the multi-locus sequence type ST313 have emerged in sub-Saharan Africa as a major cause of bacteremia in humans. The S. Typhimurium ST313 lineage is phylogenetically distinct from classical S. Typhimurium lineages, such as ST19, that cause zoonotic gastroenteritis worldwide. Previous studies have shown that the ST313 lineage has undergone genome degradation when compared to the ST19 lineage, similar to that observed for typhoidal serovars. Currently, little is known about phenotypic differences between ST313 isolates and other NTS isolates. We find that representative ST313 isolates invade non-phagocytic cells less efficiently than the classical ST19 isolates that are more commonly associated with gastroenteritis. In addition, ST313 isolates induce less Caspase-1-dependent macrophage death and IL-1ß release than ST19 isolates. ST313 isolates also express relatively lower levels of mRNA of the genes encoding the SPI-1 effector sopE2 and the flagellin, fliC, providing possible explanations for the decrease in invasion and inflammasome activation. The ST313 isolates have invasion and inflammatory phenotypes that are intermediate; more invasive and inflammatory than Salmonella enterica serovar Typhi and less than ST19 isolates associated with gastroenteritis. This suggests that both phenotypically and at the genomic level ST313 isolates are evolving signatures that facilitate a systemic lifestyle in humans.
Assuntos
Bacteriemia/patologia , Gastroenterite/patologia , Inflamassomos/metabolismo , Infecções por Salmonella/patologia , Salmonella typhimurium/imunologia , África Subsaariana , Bacteriemia/microbiologia , Gastroenterite/microbiologia , Humanos , Infecções por Salmonella/microbiologiaRESUMO
Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population.
Assuntos
Proteínas de Bactérias/genética , DNA Bacteriano/química , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Salmonella typhimurium/genética , Fatores de Virulência/genética , Adaptação Fisiológica , África Subsaariana/epidemiologia , Animais , Bovinos , DNA Bacteriano/genética , Modelos Animais de Doenças , Feminino , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Genoma Bacteriano/genética , Ilhas Genômicas , Humanos , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Filogenia , Polimorfismo de Nucleotídeo Único , Salmonella typhimurium/classificação , Salmonella typhimurium/patogenicidade , Salmonella typhimurium/fisiologia , Organismos Livres de Patógenos EspecíficosRESUMO
BACKGROUND: Nigeria suffers the world's largest malaria burden, with approximately 51 million cases and 207,000 deaths annually. As part of the country's aim to reduce by 50% malaria-related morbidity and mortality by 2013, it embarked on mass distribution of free long-lasting insecticidal nets (LLINs). METHODS: Prior to net distribution campaigns in Abia and Plateau States, Nigeria, a modified malaria indicator survey was conducted in September 2010 to determine baseline state-level estimates of Plasmodium prevalence, childhood anemia, indoor residual spraying (IRS) coverage and bednet ownership and utilization. RESULTS: Overall age-adjusted prevalence of Plasmodium infection by microscopy was similar between Abia (36.1%, 95% CI: 32.3%-40.1%; n = 2,936) and Plateau (36.6%, 95% CI: 31.3%-42.3%; n = 4,209), with prevalence highest among children 5-9 years. P. malariae accounted for 32.0% of infections in Abia, but only 1.4% of infections in Plateau. More than half of children ≤10 years were anemic, with anemia significantly higher in Abia (76.9%, 95% CI: 72.1%-81.0%) versus Plateau (57.1%, 95% CI: 50.6%-63.4%). Less than 1% of households in Abia (n = 1,305) or Plateau (n = 1,335) received IRS in the 12 months prior to survey. Household ownership of at least one bednet of any type was 10.1% (95% CI: 7.5%-13.4%) in Abia and 35.1% (95% CI: 29.2%-41.5%) in Plateau. Ownership of two or more bednets was 2.1% (95% CI: 1.2%-3.7%) in Abia and 14.5% (95% CI: 10.2%-20.3%) in Plateau. Overall reported net use the night before the survey among all individuals, children <5 years, and pregnant women was 3.4%, 6.0% and 5.7%, respectively in Abia and 14.7%, 19.1% and 21.0%, respectively in Plateau. Among households owning nets, 34.4% of children <5 years and 31.6% of pregnant women in Abia used a net, compared to 52.6% of children and 62.7% of pregnant women in Plateau. CONCLUSIONS: These results reveal high Plasmodium prevalence and childhood anemia in both states, low baseline coverage of IRS and LLINs, and sub-optimal net use-especially among age groups with highest observed malaria burden.
Assuntos
Anemia/epidemiologia , Malária/epidemiologia , Malária/prevenção & controle , Mosquiteiros , Adolescente , Adulto , Anemia/etiologia , Animais , Criança , Pré-Escolar , Culicidae/crescimento & desenvolvimento , Culicidae/parasitologia , Coleta de Dados , Características da Família , Feminino , Humanos , Insetos Vetores/crescimento & desenvolvimento , Insetos Vetores/parasitologia , Malária/complicações , Malária/parasitologia , Masculino , Pessoa de Meia-Idade , Controle de Mosquitos/métodos , Mosquiteiros/estatística & dados numéricos , Nigéria/epidemiologia , Plasmodium malariae/parasitologia , Gravidez , Prevalência , Adulto JovemRESUMO
A highly invasive form of non-typhoidal Salmonella (iNTS) disease has recently been documented in many countries in sub-Saharan Africa. The most common Salmonella enterica serovar causing this disease is Typhimurium (Salmonella Typhimurium). We applied whole-genome sequence-based phylogenetic methods to define the population structure of sub-Saharan African invasive Salmonella Typhimurium isolates and compared these to global Salmonella Typhimurium populations. Notably, the vast majority of sub-Saharan invasive Salmonella Typhimurium isolates fell within two closely related, highly clustered phylogenetic lineages that we estimate emerged independently â¼52 and â¼35 years ago in close temporal association with the current HIV pandemic. Clonal replacement of isolates from lineage I by those from lineage II was potentially influenced by the use of chloramphenicol for the treatment of iNTS disease. Our analysis suggests that iNTS disease is in part an epidemic in sub-Saharan Africa caused by highly related Salmonella Typhimurium lineages that may have occupied new niches associated with a compromised human population and antibiotic treatment.
Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Filogenia , Infecções por Salmonella , Salmonella typhimurium , África Subsaariana/epidemiologia , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Evolução Molecular , Infecções por HIV/epidemiologia , Humanos , Filogeografia , Polimorfismo de Nucleotídeo Único , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/genética , Salmonella typhimurium/classificação , Salmonella typhimurium/genética , Salmonella typhimurium/patogenicidadeRESUMO
BACKGROUND: Bloodstream infection with invasive nontyphoidal Salmonella (iNTS) is common and severe among human immunodeficiency virus (HIV)-infected adults throughout sub-Saharan Africa. The epidemiology of iNTS is poorly understood. Survivors frequently experience multiply recurrent iNTS disease, despite appropriate antimicrobial therapy, but recrudescence and reinfection have previously been difficult to distinguish. METHODS: We used high-resolution single nucleotide polymorphism (SNP) typing and whole-genome phylogenetics to investigate 47 iNTS isolates from 14 patients with multiple recurrences following an index presentation with iNTS disease in Blantyre, Malawi. We isolated nontyphoidal salmonellae organisms from blood (n = 35), bone marrow (n = 8), stool (n = 2), urine (n = 1), and throat (n = 1) samples; these isolates comprised serotypes Typhimurium (n = 43) and Enteritidis (n = 4). RESULTS: Recrudescence with identical or highly phylogenetically related isolates accounted for 78% of recurrences, and reinfection with phylogenetically distinct isolates accounted for 22% of recurrences. Both recrudescence and reinfection could occur in the same individual, and reinfection could either precede or follow recrudescence. The number of days to recurrence (23-486 d) was not different for recrudescence or reinfection. The number of days to recrudescence was unrelated to the number of SNPs accumulated by recrudescent organisms, suggesting that there was little genetic change during persistence in the host, despite exposure to multiple courses of antibiotics. Of Salmonella Typhimurium isolates, 42 of 43 were pathovar ST313. CONCLUSIONS: High-resolution whole-genome phylogenetics successfully discriminated recrudescent iNTS from reinfection, despite a high level of clonality within and among individuals, giving insights into pathogenesis and management. These methods also have adequate resolution to investigate the epidemiology and transmission of this important African pathogen.
Assuntos
Técnicas Bacteriológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Polimorfismo de Nucleotídeo Único , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/microbiologia , Salmonella typhimurium/classificação , Salmonella typhimurium/isolamento & purificação , Adolescente , Adulto , África , Idoso , Idoso de 80 Anos ou mais , Sangue/microbiologia , Medula Óssea/microbiologia , Fezes/microbiologia , Feminino , Genótipo , Humanos , Malaui , Masculino , Pessoa de Meia-Idade , Faringe/microbiologia , Filogenia , Recidiva , Salmonella typhimurium/genética , Urina/microbiologia , Adulto JovemRESUMO
Integrative and conjugative elements (ICEs) are self-mobile genetic elements found in the genomes of some bacteria. These elements may confer a fitness advantage upon their host bacteria through the cargo genes that they carry. Salmonella pathogenicity island 7 (SPI-7), found within some pathogenic strains of Salmonella enterica, possesses features indicative of an ICE and carries genes implicated in virulence. We aimed to identify and fully analyze ICEs related to SPI-7 within the genus Salmonella and other Enterobacteriaceae. We report the sequence of two novel SPI-7-like elements, found within strains of Salmonella bongori, which share 97% nucleotide identity over conserved regions with SPI-7 and with each other. Although SPI-7 within Salmonella enterica serovar Typhi appears to be fixed within the chromosome, we present evidence that these novel elements are capable of excision and self-mobility. Phylogenetic analyses show that these Salmonella mobile elements share an ancestor which existed approximately 3.6 to 15.8 million years ago. Additionally, we identified more distantly related ICEs, with distinct cargo regions, within other strains of Salmonella as well as within Citrobacter, Erwinia, Escherichia, Photorhabdus, and Yersinia species. In total, we report on a collection of 17 SPI-7 related ICEs within enterobacterial species, of which six are novel. Using comparative and mutational studies, we have defined a core of 27 genes essential for conjugation. We present a growing family of SPI-7-related ICEs whose mobility, abundance, and cargo variability indicate that these elements may have had a large impact on the evolution of the Enterobacteriaceae.
Assuntos
Proteínas de Bactérias/genética , Enterobacteriaceae/genética , Enterobacteriaceae/patogenicidade , Ilhas Genômicas , Sequências Repetitivas Dispersas , Fatores de Virulência/genética , Análise por Conglomerados , Análise Mutacional de DNA , DNA Bacteriano/química , DNA Bacteriano/genética , Evolução Molecular , Transferência Genética Horizontal , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
The taxonomic position of a Streptomyces strain isolated from a hyper-arid desert soil was established using a polyphasic approach. The organism had chemical and morphological properties typical of the genus Streptomyces and formed a phyletic line at the periphery of the Streptomyces coeruleorubidus subcluster in the 16S rRNA gene tree. DNA:DNA relatedness values between the isolate and its nearest phylogenetic neighbours, Streptomyces lomondensis NRRL 3252(T) and Streptomyces lusitanus NRRL B-12501(T) were 42.5 (±0.48)% and 25.0 (±1.78)%, respectively. The isolate was readily distinguished from these organisms using a combination of morphological and phenotypic properties. On the basis of these results, it is proposed that isolate C63(T) (CGMCC 4.6997(T), = KACC 15425(T)) be classified as the type strain of Streptomyces deserti sp. nov.
Assuntos
Clima Desértico , Microbiologia do Solo , Streptomyces/isolamento & purificação , Carbono/metabolismo , Chile , Meios de Cultura , DNA Bacteriano/genética , DNA Ribossômico/genética , Umidade , Dados de Sequência Molecular , Nitrogênio/metabolismo , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , Ribotipagem , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Streptomyces/classificação , Streptomyces/genética , Streptomyces/crescimento & desenvolvimento , Streptomyces/metabolismoRESUMO
The taxonomic position of a Streptomyces strain isolated from an extreme hyper-arid soil sample collected from the Atacama Desert was determined using a polyphasic approach. The strain, isolate C60(T), had chemical and morphological features typical of members of the genus Streptomyces and formed a distinct phyletic line in the Streptomyces 16S rRNA gene tree, together with the type strain of Streptomyces radiopugnans. The two strains were distinguished readily using a combination of phenotypic properties and by a DNA-DNA relatedness value of 23.17 (± 0.95)%. On the basis of these genotypic and phenotypic data, it is proposed that isolate C60(T) (=CGMCC 4.7018(T)=KACC 15492(T)) be classified in the genus Streptomyces as Streptomyces atacamensis sp. nov.
Assuntos
Filogenia , Microbiologia do Solo , Streptomyces/classificação , Técnicas de Tipagem Bacteriana , Chile , DNA Bacteriano/genética , Ácidos Graxos/análise , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Esporos Bacterianos/ultraestrutura , Streptomyces/genética , Streptomyces/isolamento & purificação , Vitamina K 2/análiseRESUMO
The metabolic profile of Streptomyces sp. strain C34, isolated from the Chilean hyper-arid Atacama Desert soil, is dependent on the culture media used for its growth. The application of an OSMAC approach on this strain using a range of cultivation media resulted in the isolation and identification of three new compounds from the rare class of 22-membered macrolactone polyketides, named chaxalactins A-C (1-3). In addition, the known compounds deferroxamine E (4), hygromycin A (5), and 5â³-dihydrohygromycin A (6) were detected. The isolated compounds were characterized by NMR spectroscopy and accurate mass spectrometric analysis. Compounds 1-3 displayed strong activity against Gram-positive but weak activity Gram-negative strains tested.
Assuntos
Antibacterianos/isolamento & purificação , Macrolídeos/isolamento & purificação , Streptomyces , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Cinamatos/química , Cinamatos/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Higromicina B/análogos & derivados , Higromicina B/química , Higromicina B/isolamento & purificação , Listeria monocytogenes/efeitos dos fármacos , Macrolídeos/química , Macrolídeos/farmacologia , Metaboloma , Testes de Sensibilidade Microbiana , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Streptomyces/química , Streptomyces/genética , Streptomyces/metabolismo , Vibrio/efeitos dos fármacosRESUMO
Streptomyces sp. strain C34, isolated from soil collected in the Chilean hyper-arid Atacama Desert, was cultured on different media, resulting in the isolation and identification of four new ansamycin-type polyketides. The organism was selected for chemical investigation on the basis of a genome-mining PCR-based experiment targeting the gene encoding rifamycin-specific 3-amino-5-hydroxybenzoic acid synthetase (AHBA). The isolated compounds were structurally characterized using NMR and MS techniques and named chaxamycins A-D (1-4). Compounds 1-4 were tested for their antibacterial activity against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 and for their ability to inhibit the intrinsic ATPase activity of the heat shock protein 90 (Hsp90). Chaxamycin D (4), which showed a selective antibacterial activity against S. aureus ATCC 25923, was tested further against a panel of MRSA clinical isolates. In a virtual screening experiment, chaxamycins A-D (1-4) have also been docked into the ATP-binding pocket in the N-terminal domain of the Hsp90, and the observed interactions are discussed.
Assuntos
Antibacterianos/isolamento & purificação , Lactamas Macrocíclicas/isolamento & purificação , Lactamas Macrocíclicas/farmacologia , Streptomyces/química , Adenosina Trifosfatases/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Hidroliases/genética , Hidroliases/metabolismo , Lactamas Macrocíclicas/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Estrutura MolecularRESUMO
We evaluated the effect of annual ivermectin (IV) distribution for onchocerciasis on the prevalence of soil transmitted helminth (STH) infections in school-aged (SAC) and preschool-aged (PAC) children by comparing children in villages that had received treatment for 13 years to those from socioeconomically similar villages in untreated areas. We enrolled 1,031 SAC and 211 PAC for Kato Katz examinations. Treated areas had a lower prevalence of Ascaris (SAC: 3% versus 12%, P < 0.0001; PAC: 3% versus 10%, P < 0.051) and Trichuris (SAC: 6% versus 10%, P = 0.012; PAC: 1% versus 8%, P = 0.019), but not hookworm (SAC: 38% versus 42%, P = 0.20; PAC: 21% versus 27%, P = 0.30). The prevalence of Ascaris or Trichuris in treated areas was below the WHO threshold for mass antihelminthic treatment (MDA), but not for hookworm. We conclude that benzimidazole MDA in IV treatment areas is indicated to effectively control hookworm.
Assuntos
Antiparasitários/uso terapêutico , Helmintos/isolamento & purificação , Intestinos/parasitologia , Ivermectina/uso terapêutico , Oncocercose/tratamento farmacológico , Adolescente , Animais , Criança , Pré-Escolar , Humanos , Ivermectina/farmacologia , PrevalênciaRESUMO
The taxonomic positions of three Lechevalieria-like strains isolated from hyperarid soils of the Atacama Desert, Chile, were established by using a polyphasic approach. The organisms had chemical and morphological properties consistent with their classification in the genus Lechevalieria. They formed a distinct subclade in the Lechevalieria 16S rRNA gene clade and were most closely related to the type strain of Lechevalieria xinjiangensis. DNA-DNA relatedness data showed that each of the isolates and Lechevalieria xinjiangensis DSM 45081(T) belong to distinct genomic species. The new isolates and the type strains of recognized Lechevalieria species were readily distinguished based on a number of phenotypic properties. A combination of the genotypic and phenotypic data showed that the three isolates represent three novel species of the genus Lechevalieria. The names proposed for these taxa are Lechevalieria atacamensis sp. nov. (type strain C61(T) =CGMCC 4.5536(T) =NRRL B-24706(T)), Lechevalieria deserti sp. nov. (type strain C68(T) =CGMCC 4.5535(T) =NRRL B-24707(T)) and Lechevalieria roselyniae sp. nov. (type strain C81(T) =CGMCC 4.5537(T) =NRRL B-24708(T)).