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1.
PLoS Pathog ; 17(12): e1010121, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34871327

RESUMEN

Type VII secretion systems (T7SS) have been identified in Actinobacteria and Firmicutes and have been shown to secrete effector proteins with functions in virulence, host toxicity, and/or interbacterial killing in a few genera. Bioinformatic analysis indicates that isolates of Group B Streptococcus (GBS) encode at least four distinct subtypes of T7SS machinery, three of which encode adjacent putative T7SS effectors with WXG and LXG motifs. However, the function of T7SS in GBS pathogenesis is unknown. Here we assessed the role of the most abundant GBS T7SS subtype during GBS pathogenesis. In a murine model of hematogenous meningitis, mice infected with GBS lacking a functional T7SS or lacking the secreted WXG100 effector EsxA exhibited less mortality, lower bacterial burdens in tissues, and decreased inflammation in the brain compared to mice infected with the parental GBS strain. We further showed that this T7SS induces cytotoxicity in brain endothelium and that EsxA contributes to these cytotoxicity phenotypes in a WXG motif-dependent manner. Finally, we determined that EsxA is a pore-forming protein, thus demonstrating the first role for a non-mycobacterial EsxA homolog in pore formation. This work reveals the importance of a T7SS in host-GBS interactions and has implications for T7SS effector function in other Gram-positive bacteria.


Asunto(s)
Infecciones Estreptocócicas/metabolismo , Streptococcus agalactiae/patogenicidad , Sistemas de Secreción Tipo VII/metabolismo , Virulencia/fisiología , Animales , Proteínas Bacterianas/metabolismo , Células Cultivadas , Humanos , Ratones , Streptococcus agalactiae/metabolismo
2.
Front Immunol ; 12: 786602, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34899755

RESUMEN

Streptococcus agalactiae, also known as group B streptococcus (GBS), can cause pneumonia, meningitis, and bacteremia, making it a pathogen that can increase the risk of death in newborns and immunodeficient individuals. Neutrophils are the first barrier to a host's innate immune defense against these infections. Fpr2(Formyl peptide receptor 2) is an important chemotactic receptor of neutrophils, though its activation would cause pro- and anti-inflammatory effects. In this study, we found that mice without Fpr2 receptor were highly susceptible to GBS infections. These mice demonstrated decreased chemotaxis to neutrophils, decreased bactericidal ability of neutrophils, and high mortality. RNA-seq and Luminex assay indicated that Fpr2 activates key signal molecules downstream and produces chemokines CXCL1/2 to chemotaxis neutrophils. Like Fpr2-/-, CXCL1/2 or neutrophil depletion impairs host's ability to defend against GBS infection. Altogether, these data indicate that Fpr2 contributes to a host's ability to control GBS infection and that a lack of Fpr2 was associated with selective impairment during the production of chemokines CXCL1 and CXCL2 as well as neutrophil recruitment. Here, We clarified that Fpr2, as a chemotactic receptor, could not only directly chemotactic neutrophils, but also regulate the production of chemokines to control infection by chemotactic neutrophils.


Asunto(s)
Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/metabolismo , Quimiotaxis de Leucocito , Infiltración Neutrófila , Neutrófilos/inmunología , Receptores de Formil Péptido/metabolismo , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae/inmunología , Animales , Modelos Animales de Enfermedad , Interacciones Huésped-Patógeno , Inmunidad Innata , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/metabolismo , Neutrófilos/microbiología , Receptores de Formil Péptido/genética , Transducción de Señal , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/metabolismo , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/patogenicidad , Factores de Tiempo
3.
Microbiologyopen ; 10(6): e1256, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34964296

RESUMEN

Although Streptococcus agalactiae periprosthetic joint infection (PJI) is not as prevalent as staphylococcal PJI, invasive S. agalactiae infection is not uncommon. Here, RNA-seq was used to perform transcriptomic analysis of S. agalactiae PJI using fluid derived from sonication of explanted arthroplasties of subjects with S. agalactiae PJI, with results compared to those of S. agalactiae strain NEM316 grown in vitro. A total of 227 genes with outlier expression were found (164 upregulated and 63 downregulated) between PJI sonicate fluid and in vitro conditions. Functional enrichment analysis showed genes involved in mobilome and inorganic ion transport and metabolism to be most enriched. Genes involved in nickel, copper, and zinc transport, were upregulated. Among known virulence factors, cyl operon genes, encoding ß-hemolysin/cytolysin, were consistently highly expressed in PJI versus in vitro. The data presented provide insight into S. agalactiae PJI pathogenesis and may be a resource for identification of novel PJI therapeutics or vaccines against invasive S. agalactiae infections.


Asunto(s)
Prótesis Articulares/efectos adversos , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/genética , Transcriptoma , Adulto , Anciano , Adhesión Bacteriana/genética , Biopelículas/crecimiento & desarrollo , Femenino , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos , Genoma Bacteriano , Humanos , Masculino , Persona de Mediana Edad , RNA-Seq , Streptococcus agalactiae/patogenicidad , Streptococcus agalactiae/fisiología , Factores de Virulencia/genética , Secuenciación Completa del Genoma
4.
Emerg Microbes Infect ; 10(1): 2113-2124, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34727007

RESUMEN

The clustered regularly interspaced palindromic repeats (CRISPR)-Cas (CRISPR-associated) system is a prokaryotic defence against invading mobile genetic elements, such as bacteriophages or exogenous plasmids. Beyond this, this system has been shown to play an important role in controlling the virulence of some bacterial pathogens. Streptococcus agalactiae strain GD201008-001, a causative agent of septicemia and meningitis in tilapia, contains a single type II CRISPR-Cas system with Cas9 as a signature protein. In this study, we found that the deletion of CRISPR significantly reduced adhesion, invasion, cytotoxicity and haemolysis, and caused severely attenuated virulence in the piscine S. agalactiae strain. RNA-Seq identified 236 endogenous genes regulated by CRISPR, with 159 genes upregulated and 77 genes downregulated. The resulting change in gene transcription by CRISPR was much more pronounced than that by cas9 in this bacterium, indicating CRISPR-mediated endogenous gene regulation was mostly independently of cas9. Subsequent studies showed that CovR/S two-component system was transcriptionally upregulated due to CRISPR deletion, which repressed the expression of the cylE gene coding for a cytolytic toxin, and thus decreased the activity of ß-haemolysin/cytolysin. However, upregulation of CovR/S was not the contributor to the attenuation phenotype of ΔCRISPR. Further, we demonstrated that CRISPR is capable of repressing the expression of Toll-like receptor 2 (TLR2)-activating lipoprotein Sag0671 and thus dampens the innate immune response. This study revealed that the CRISPR system of S. agalactiae exhibited extraordinary potential capability in the regulation of endogenous transcripts, which contributes to bacterial innate immune evasion and virulence.


Asunto(s)
Proteínas Bacterianas/genética , Enfermedades de los Peces/microbiología , Regulación Bacteriana de la Expresión Génica , Infecciones Estreptocócicas/veterinaria , Streptococcus agalactiae/patogenicidad , Animales , Proteínas Bacterianas/metabolismo , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Femenino , Peces , Ratones , Ratones Endogámicos C57BL , Perforina/genética , Perforina/metabolismo , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/genética , Streptococcus agalactiae/fisiología , Virulencia
5.
Biomolecules ; 11(10)2021 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-34680142

RESUMEN

DnaJ proteins or heat shock protein 40s (HSP40s) form one of the largest heat shock protein families. In this study, 2 cDNAs encoding Nile tilapia (Oreochromis niloticus) DnaJ proteins (On-DnaJ B9b and On-DnaJ C3a) were successfully cloned and characterized. The structures and organizations of these two genes are first reported in the present study. On-DnaJ B9b is approximately 2.1 kb long and contains 2 exons and 1 intron, while On-DnaJ C3a is approximately 12 kb long and contains 12 exons and 11 introns. Under normal conditions, On-DnaJ B9b mRNA is highly expressed in gonad and trunk kidney tissues, while On-DnaJ C3a transcripts are abundantly expressed in gills, intestine, liver, and trunk kidney tissues. Following pathogenic infections, the expression of both genes is induced in the liver, spleen and head kidney tissues of Nile tilapia that were infected with two virulent pathogenic bacteria, Streptococcus agalactiae and Flavobacterium columnare. Silencing of these two genes was first carried out, and the results clearly indicated their crucial roles under both heat and bacterial stress conditions. The fundamental knowledge obtained from this study indicates the characteristic basic biofunctions of heat shock proteins in the regulation of intracellular proteins during infection, which involve preventing protein aggregation, promoting protein refolding, and activating unfolded protein degradation.


Asunto(s)
Cíclidos/genética , Proteínas del Choque Térmico HSP40/genética , Proteínas de Choque Térmico/genética , Inmunidad Innata/genética , Animales , Cíclidos/inmunología , Cíclidos/microbiología , Cíclidos/fisiología , Flavobacterium/patogenicidad , Regulación de la Expresión Génica/inmunología , Calor/efectos adversos , Riñón/metabolismo , Riñón/microbiología , Hígado/metabolismo , Hígado/microbiología , Bazo/metabolismo , Bazo/microbiología , Streptococcus agalactiae/patogenicidad
6.
PLoS Genet ; 17(9): e1009761, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34491998

RESUMEN

Virulence of the neonatal pathogen Group B Streptococcus is under the control of the master regulator CovR. Inactivation of CovR is associated with large-scale transcriptome remodeling and impairs almost every step of the interaction between the pathogen and the host. However, transcriptome analyses suggested a plasticity of the CovR signaling pathway in clinical isolates leading to phenotypic heterogeneity in the bacterial population. In this study, we characterized the CovR regulatory network in a strain representative of the CC-17 hypervirulent lineage responsible of the majority of neonatal meningitis. Transcriptome and genome-wide binding analysis reveal the architecture of the CovR network characterized by the direct repression of a large array of virulence-associated genes and the extent of co-regulation at specific loci. Comparative functional analysis of the signaling network links strain-specificities to the regulation of the pan-genome, including the two specific hypervirulent adhesins and horizontally acquired genes, to mutations in CovR-regulated promoters, and to variability in CovR activation by phosphorylation. This regulatory adaptation occurs at the level of genes, promoters, and of CovR itself, and allows to globally reshape the expression of virulence genes. Overall, our results reveal the direct, coordinated, and strain-specific regulation of virulence genes by the master regulator CovR and suggest that the intra-species evolution of the signaling network is as important as the expression of specific virulence factors in the emergence of clone associated with specific diseases.


Asunto(s)
Proteínas Bacterianas/fisiología , Redes Reguladoras de Genes , Streptococcus agalactiae/patogenicidad , Factores de Virulencia/fisiología , Virulencia/genética , Proteínas Bacterianas/genética , Cromosomas Bacterianos , Genes Bacterianos , Interacciones Huésped-Patógeno , Humanos , Regiones Promotoras Genéticas , Profagos/genética , Streptococcus agalactiae/genética , Transcripción Genética/fisiología , Factores de Virulencia/genética
7.
PLoS Pathog ; 17(8): e1009791, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34370789

RESUMEN

In many Gram-positive bacteria, the redox-sensing transcriptional repressor Rex controls central carbon and energy metabolism by sensing the intra cellular balance between the reduced and oxidized forms of nicotinamide adenine dinucleotide; the NADH/NAD+ ratio. Here, we report high-resolution crystal structures and characterization of a Rex ortholog (Gbs1167) in the opportunistic pathogen, Streptococcus agalactiae, also known as group B streptococcus (GBS). We present structures of Rex bound to NAD+ and to a DNA operator which are the first structures of a Rex-family member from a pathogenic bacterium. The structures reveal the molecular basis of DNA binding and the conformation alterations between the free NAD+ complex and DNA-bound form of Rex. Transcriptomic analysis revealed that GBS Rex controls not only central metabolism, but also expression of the monocistronic rex gene as well as virulence gene expression. Rex enhances GBS virulence after disseminated infection in mice. Mechanistically, NAD+ stabilizes Rex as a repressor in the absence of NADH. However, GBS Rex is unique compared to Rex regulators previously characterized because of its sensing mechanism: we show that it primarily responds to NAD+ levels (or growth rate) rather than to the NADH/NAD+ ratio. These results indicate that Rex plays a key role in GBS pathogenicity by modulating virulence factor gene expression and carbon metabolism to harvest nutrients from the host.


Asunto(s)
Proteínas Bacterianas/genética , Productos del Gen rex/genética , NAD/deficiencia , Regulón , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/patogenicidad , Virulencia , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Cristalografía por Rayos X , Femenino , Perfilación de la Expresión Génica , Productos del Gen rex/química , Productos del Gen rex/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Unión Proteica , Conformación Proteica , Infecciones Estreptocócicas/metabolismo
8.
Acta Obstet Gynecol Scand ; 100(10): 1814-1821, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34255864

RESUMEN

INTRODUCTION: Vaginal colonization with Streptococcus agalactiae (group B streptococci) is hypothesized to constitute a risk factor for preterm prelabor rupture of membranes. In vitro studies have shown that S. agalactiae strains isolated from infants with neonatal sepsis adhere to chorion cells of the human chorioamniotic membrane. However, it is still unknown whether S. agalactiae strains penetrate the chorioamniotic membranes and whether S. agalactiae colonization affects the biomechanical properties of the membranes and thus contributes to increased risk of preterm prelabor rupture. The aim of this in vitro study was to explore if different strains of S. agalactiae penetrate and affect the biomechanical properties of human chorioamniotic membranes. MATERIAL AND METHODS: Three different strains of S. agalactiae were obtained, one from an early-onset neonatal infection, one from a case of preterm prelabor rupture of membranes and one from a healthy pregnant carrier. Chorioamniotic membranes from elective cesarean deliveries were either incubated with S. agalactiae or mounted in a two-chamber incubation cell generating a "maternal" and a "fetal" chamber and incubated with S. agalactiae in the maternal chamber. Subsequently the membranes were examined to evaluate S. agalactiae attachment, penetration and the effect on the biomechanical properties. RESULTS: At 5 h after incubation, S. agalactiae adhered to the chorioamniotic membranes with increased number at 20 h. Streptococcus agalactiae did not penetrate the membranes even after 20 h of incubation. Streptococcus agalactiae increased the ultimate tensile stress needed to rupture the membranes and increased the work needed to rupture the membranes as well as the elastic modulus. CONCLUSIONS: Human chorioamniotic membranes constitute a physical barrier against S. agalactiae infections. Moreover, S. agalactiae infection leads to increased strength of the membranes.


Asunto(s)
Corion/microbiología , Rotura Prematura de Membranas Fetales/microbiología , Complicaciones Infecciosas del Embarazo , Infecciones Estreptocócicas , Streptococcus agalactiae/patogenicidad , Femenino , Humanos , Técnicas In Vitro , Embarazo
9.
Front Immunol ; 12: 667781, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34093564

RESUMEN

Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that especially plays an important role in innate immune. However, the roles of LECT2 in the immune response of the economically important fish Nile tilapia (Oreochromis niloticus) against bacterial infection remains unclear. In this study, a lect2 gene from Nile tilapia (On-lect2) was identified, and its roles in the fish's immune response against bacterial infection were determined and characterised. On-lect2 contains an open reading frame of 456 bp that encodes a peptide of 151 amino acids, as well as the conservative peptidase M23 domain. On-LECT2 is 62%-84% identical to other fish species and about 50% identical to mammals. The highest transcriptional level of On-lect2 was detected in the liver, whereas the lowest levels were detected in the other tissues. Moreover, the On-LECT2 protein is located mainly in the brain and head kidney. The transcriptional levels of On-lect2 substantially increased in the head kidney, brain, liver and spleen after Streptococcus agalactiae infection. Knockdown On-lect2 led to higher mortality due to liver necrosis or haemorrhage and splenomegaly. In vitro analysis indicated that the recombinant protein of On-LECT2 improved phagocytic activity of head kidney-derived macrophages. In vivo challenge experiments revealed several functions of On-LECT2 in the immune response of Nile tilapia against bacterial infection, including promotion of inflammation, reduction of tissue damages and improvement of survival rate.


Asunto(s)
Cíclidos/microbiología , Enfermedades de los Peces/prevención & control , Proteínas de Peces/metabolismo , Inmunidad Innata , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Macrófagos/microbiología , Infecciones Estreptocócicas/veterinaria , Streptococcus agalactiae/patogenicidad , Animales , Cíclidos/genética , Cíclidos/inmunología , Cíclidos/metabolismo , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/metabolismo , Enfermedades de los Peces/microbiología , Proteínas de Peces/genética , Interacciones Huésped-Patógeno , Péptidos y Proteínas de Señalización Intercelular/genética , Macrófagos/inmunología , Macrófagos/metabolismo , Infecciones Estreptocócicas/metabolismo , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae/inmunología , Transcripción Genética
10.
PLoS One ; 16(6): e0253242, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34129624

RESUMEN

Streptococcus agalactiae (group B streptococcus or GBS) is a commensal bacterium that can frequently behave as a pathogen, particularly in the neonatal period and in the elderly. The gut is a primary site of GBS colonization and a potential port of entry during neonatal infections caused by hypervirulent clonal complex 17 (CC17) strains. Here we studied the interactions between the prototypical CC17 BM110 strain and polarized enterocytes using the Caco-2 cell line. GBS could adhere to and invade these cells through their apical or basolateral surfaces. Basolateral invasion was considerably more efficient than apical invasion and predominated under conditions resulting in weakening of cell-to-cell junctions. Bacterial internalization occurred by a mechanism involving caveolae- and lipid raft-dependent endocytosis and actin re-organization, but not clathrin-dependent endocytosis. In the first steps of Caco-2 invasion, GBS colocalized with the early endocytic marker EEA-1, to later reside in acidic vacuoles. Taken together, these data suggest that CC17 GBS selectively adheres to the lateral surface of enterocytes from which it enters through caveolar lipid rafts using a classical, actin-dependent endocytic pathway. These data may be useful to develop alternative preventive strategies aimed at blocking GBS invasion of the intestinal barrier.


Asunto(s)
Enterocitos/microbiología , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/patogenicidad , Adhesión Bacteriana , Células CACO-2/microbiología , Endocitosis , Humanos , Uniones Intercelulares/microbiología , Microscopía Fluorescente , Streptococcus agalactiae/fisiología , Virulencia
11.
Pediatr Infect Dis J ; 40(7): 663-668, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34097659

RESUMEN

BACKGROUND: Prevention strategies can reduce the incidence of early-onset group B Streptococcus (GBS) neonatal sepsis (EOGBS). Rates of GBS colonization and infection vary among regions within China. China has not adopted a unified prevention strategy. METHODS: To assess strategies to reduce EOGBS in China, models were developed to quantify residual EOGBS rates with intrapartum antibiotic prophylaxis in infants ≥ 35 weeks' gestation in risk factor-based and antepartum screening-based strategies. Maternal GBS colonization rates and EOGBS incidence in 3 regions of China (A: Xiamen of Fujian province, B: Shanghai and C: Liuzhou of Guangxi province) were estimated from published data. RESULTS: Estimates for GBS colonization and attack rates were 21.6%, 11.7% and 6.1% and 1.79, 1.79 and 0.58 per 1000 live births for regions A, B and C, respectively. Modeling predicted that strategies including screening cultures beginning at 36 weeks' gestation and intrapartum antibiotic prophylaxis in 90% of eligible parturients could reduce EOGBS incidence to 0.44, 0.50 and 0.16 per 1000 live births in these regions. In region C, the expected EOGBS rate could be reduced to 0.28 per 1000 using a risk factor-based strategy. CONCLUSIONS: Different strategies for preventing EOGBS may be needed in different regions of mainland China. Screening strategies may be most appropriate in regions with higher attack rates, even with moderate levels of maternal GBS colonization. In areas with low attack rates, risk factor strategies that reduce morbidity by at least one-third may suffice.


Asunto(s)
Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Sepsis Neonatal/prevención & control , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae/patogenicidad , Profilaxis Antibiótica , China/epidemiología , Femenino , Geografía , Edad Gestacional , Humanos , Incidencia , Recién Nacido , Sepsis Neonatal/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/prevención & control , Factores de Riesgo , Infecciones Estreptocócicas/sangre , Infecciones Estreptocócicas/epidemiología
12.
Future Microbiol ; 16: 671-685, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34098731

RESUMEN

Group B Streptococcus (GBS) is the main pathogen of perinatal infection. It can lead to adverse pregnancy, maternal infection, premature delivery, abortion, stillbirth and a series of adverse maternal and infant outcomes such as neonatal sepsis, meningitis or pneumonia during delivery. In order to reduce the infection of perinatal pregnant and the adverse pregnancy outcome, more attention should be paid in the clinical practice, screening efforts, universal detection of GBS infection for pregnant women and preventive treatment for the possible mother infant infection. In this study, the biological characteristics, immunophenotype, major pathogenic mechanism, laboratory test methods and clinical significance of GBS are summarized.


Asunto(s)
Infecciones Estreptocócicas/diagnóstico , Streptococcus agalactiae , Femenino , Humanos , Recién Nacido , Embarazo , Streptococcus agalactiae/aislamiento & purificación , Streptococcus agalactiae/patogenicidad
13.
Res Vet Sci ; 138: 109-115, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34126449

RESUMEN

Streptococcus agalactiae (GBS) is an important pathogen that has increasingly received attention for its role in invasive infections and its broad host range. Research on the regulation of gene expression could illuminate GBS pathogenesis. We previously identified a novel transcriptional regulator XtgS, which is a negative regulator of GBS pathogenicity. Here, we demonstrate that XtgS overexpression significantly attenuated GBS virulence in zebrafish infection tests, and XtgS indirectly downregulated the transcription of two iron transport systems based on the results of transcriptomic analysis, electrophoretic mobility shift assays (EMSAs) and lacZ fusion assays. Subsequent studies verified that the inactivation of iron transport system 1 resulted in GBS excessive iron accumulation and attenuated virulence. Thus, we infer that the downregulation of iron transport system 1 caused by XtgS overexpression probably attenuates bacterial virulence, which partially clarifies the mechanism by which XtgS alleviates the pathogenesis. These findings provide new insights into the relationship between exogenous transcriptional regulation and bacterial virulence.


Asunto(s)
Proteínas Bacterianas/genética , Enfermedades de los Peces/microbiología , Hierro/metabolismo , Infecciones Estreptocócicas/veterinaria , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidad , Factores de Transcripción/genética , Pez Cebra , Animales , Proteínas Bacterianas/metabolismo , Infecciones Estreptocócicas/microbiología , Factores de Transcripción/metabolismo , Virulencia/genética
14.
BMC Microbiol ; 21(1): 139, 2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33947330

RESUMEN

BACKGROUND: The information on antibiotic resistance and molecular features of Group B Streptococcus (GBS) are essential for epidemiological purposes as well as vaccine development. Therefore, we aimed to assess the antimicrobial resistance profiles and molecular characteristics of GBS isolates in Isfahan, Iran. A total number of 72 colonizing and invasive GBS were collected from pregnant and non-pregnant women. The GBS isolates were analyzed for resistance profiles, capsular genotyping, and detection of PI-1, PI-2a, PI-2b, hvgA, ermB, ermTR, lnuB and, mefA genes. Besides, erythromycin-resistant strains were subjected to multilocus sequence typing (MLST). RESULTS: The prevalence of colonizing and invasive GBS were 11 and 0.05%, respectively. The frequency of capsular serotypes was as follows: III (26.3%), Ia (20.83%), Ib and V (each 15.2%), IV (9.7%), II (8.3%), VII (2.7%), and VI (1.3%). Overall frequencies of PIs were as follows: PI-1, 37.5%, PI-1 + PI-2a, 30.5%, PI-1 + PI-2b, 29.1% and PI-2b, 2.7%. Two maternal colonizing GBS (2.6%) were hvgA positive and were belonged to ST-17/CPS-III/PI-1 + PI-2b lineage. Among 30(41.6%) erythromycin resistant GBS, 21 isolates (70%) harbored ermB gene, followed by ermTR (23.3%) and mefA (10%). One clindamycin-resistant isolate harbored the lnuB gene. MLST analysis revealed the following five clonal complexes (CCs) and nine STs: (CC-19/ST-335, ST-19, and ST-197), (CC-12/ST-43, ST-12), (CC-23/ST-163, ST-23), (CC-17/ST-17) and (CC-4/ST-16). CONCLUSION: The study shows an alarmingly high prevalence of erythromycin-resistant GBS in Iran. In addition, we report dissemination of ST-335/CPS-III clone associated with tetracycline and erythromycin resistance in our region. The distribution of capsular and pilus genotypes varies between invasive and colonizing GBS that could be helpful for vaccine development.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/efectos de los fármacos , Streptococcus agalactiae/genética , Femenino , Fimbrias Bacterianas/genética , Genes Bacterianos/genética , Humanos , Irán/epidemiología , Embarazo , Prevalencia , Serotipificación , Streptococcus agalactiae/clasificación , Streptococcus agalactiae/patogenicidad
15.
BMC Microbiol ; 21(1): 145, 2021 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-33985431

RESUMEN

BACKGROUND: Group B streptococci (GBS) are important neonatal bacterial pathogens that can cause severe invasive disease in the newborn. It is thought that in many cases of invasive neonatal GBS disease, the bacteria ascend the vagina into the uterus and infect the amniotic fluid surrounding the fetus. Important constituents of this environment include the polyols or sugar alcohols of which erythritol, sorbitol and mannitol are examples. The aim of our study was to investigate the effect of polyols on GBS grown in media containing these sugar alcohols. RESULTS: GBS incubated in varying concentrations of polyols (erythritol, sorbitol or mannitol) did not display any significant enhancement or inhibition of bacterial growth. However, growth of GBS in the presence of erythritol significantly increased the surface expression of GBS-PGK (a plasminogen binding protein) 1.25 to 1.5-fold depending on the erythritol concentration and significantly enhanced the survival in human blood 3X to 18X depending on the concentration of polyol used. Interestingly, GBS grown in 1% erythritol significantly increased invasion by the bacteria of HeLa cells (epithelial cell line) (150% vs 100%) however, at higher concentrations (2% or 4% of polyol) the number of CFUs was significantly reduced (55-75% vs 100%) suggesting higher concentrations of polyols may inhibit invasion. Erythritol also increased GBS hemolytic activity as well as enhancing biofilm formation 1.4X to 3.3X depending on the concentration of polyol used. CONCLUSIONS: GBS grown in the presence of polyols alters the bacteria's phenotype resulting in changes associated with GBS virulence. This effect was greatest for the polyol erythritol.


Asunto(s)
Eritritol/metabolismo , Manitol/metabolismo , Polímeros/metabolismo , Sorbitol/metabolismo , Streptococcus agalactiae/crecimiento & desarrollo , Células HeLa , Humanos , Fenotipo , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/metabolismo , Streptococcus agalactiae/patogenicidad , Virulencia
16.
mSphere ; 6(3)2021 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-34011683

RESUMEN

Zinc is an essential trace element for normal bacterial physiology but, divergently, can intoxicate bacteria at high concentrations. Here, we define the molecular systems for Zn detoxification in Streptococcus agalactiae, also known as group B streptococcus, and examine the effects of resistance to Zn stress on virulence. We compared the growth of wild-type bacteria and mutants deleted for the Zn exporter, czcD, and the response regulator, sczA, using Zn-stress conditions in vitro Macrophage antibiotic protection assays and a mouse model of disseminated infection were used to assess virulence. Global bacterial transcriptional responses to Zn stress were defined by RNA sequencing and quantitative reverse transcription-PCR. czcD and sczA enabled S. agalactiae to survive Zn stress, with the putative CzcD efflux system activated by SczA. Additional genes activated in response to Zn stress encompassed divalent cation transporters that contribute to regulation of Mn and Fe homeostasis. In vivo, the czcD-sczA Zn management axis supported virulence in the blood, heart, liver, and bladder. Additionally, several genes not previously linked to Zn stress in any bacterium, including, most notably, arcA for arginine deamination, also mediated resistance to Zn stress, representing a novel molecular mechanism of bacterial resistance to metal intoxication. Taken together, these findings show that S. agalactiae responds to Zn stress by sczA regulation of czcD, with additional novel mechanisms of resistance supported by arcA, encoding arginine deaminase. Cellular management of Zn stress in S. agalactiae supports virulence by facilitating bacterial survival in the host during systemic infection.IMPORTANCE Streptococcus agalactiae, also known as group B streptococcus, is an opportunistic pathogen that causes various diseases in humans and animals. This bacterium has genetic systems that enable zinc detoxification in environments of metal stress, but these systems remain largely undefined. Using a combination of genomic, genetic, and cellular assays, we show that this pathogen controls Zn export through CzcD to manage Zn stress and utilizes a system of arginine deamination never previously linked to metal stress responses in bacteria to survive metal intoxication. We show that these systems are crucial for survival of S. agalactiae in vitro during Zn stress and also enhance virulence during systemic infection in mice. These discoveries establish new molecular mechanisms of resistance to metal intoxication in bacteria; we suggest these mechanisms operate in other bacteria as a way to sustain microbial survival under conditions of metal stress, including in host environments.


Asunto(s)
Regulación Bacteriana de la Expresión Génica , Metales/farmacología , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/efectos de los fármacos , Streptococcus agalactiae/patogenicidad , Estrés Fisiológico , Zinc/metabolismo , Animales , Línea Celular , Perfilación de la Expresión Génica , Humanos , Proteínas de Transporte de Membrana , Ratones , Ratones Endogámicos C57BL , Streptococcus agalactiae/genética , Streptococcus agalactiae/crecimiento & desarrollo , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/genética , Transcripción Genética , Células U937 , Virulencia , Zinc/análisis
17.
Genet Sel Evol ; 53(1): 37, 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33882834

RESUMEN

BACKGROUND: Streptococcosis is a major bacterial disease in Nile tilapia that is caused by Streptococcus agalactiae infection, and development of resistant strains of Nile tilapia represents a sustainable approach towards combating this disease. In this study, we performed a controlled disease trial on 120 full-sib families to (i) quantify and characterize the potential of genomic selection for survival to S. agalactiae infection in Nile tilapia, and (ii) identify the best genomic model and the optimal density of single nucleotide polymorphisms (SNPs) for this trait. METHODS: In total, 40 fish per family (15 fish intraperitoneally injected and 25 fish as cohabitants) were used in the challenge test. Mortalities were recorded every 3 h for 35 days. After quality control, genotypes (50,690 SNPs) and phenotypes (0 for dead and 1 for alive) for 2472 cohabitant fish were available. Genetic parameters were obtained using various genomic selection models (genomic best linear unbiased prediction (GBLUP), BayesB, BayesC, BayesR and BayesS) and a traditional pedigree-based model (PBLUP). The pedigree-based analysis used a deep 17-generation pedigree. Prediction accuracy and bias were evaluated using five replicates of tenfold cross-validation. The genomic models were further analyzed using 10 subsets of SNPs at different densities to explore the effect of pruning and SNP density on predictive accuracy. RESULTS: Moderate estimates of heritabilities ranging from 0.15 ± 0.03 to 0.26 ± 0.05 were obtained with the different models. Compared to a pedigree-based model, GBLUP (using all the SNPs) increased prediction accuracy by 15.4%. Furthermore, use of the most appropriate Bayesian genomic selection model and SNP density increased the prediction accuracy up to 71%. The 40 to 50 SNPs with non-zero effects were consistent for all BayesB, BayesC and BayesS models with respect to marker id and/or marker locations. CONCLUSIONS: These results demonstrate the potential of genomic selection for survival to S. agalactiae infection in Nile tilapia. Compared to the PBLUP and GBLUP models, Bayesian genomic models were found to boost the prediction accuracy significantly.


Asunto(s)
Resistencia a la Enfermedad/genética , Enfermedades de los Peces/genética , Modelos Genéticos , Polimorfismo de Nucleótido Simple , Infecciones Estreptocócicas/genética , Tilapia/genética , Animales , Teorema de Bayes , Linaje , Carácter Cuantitativo Heredable , Selección Genética , Selección Artificial , Infecciones Estreptocócicas/veterinaria , Streptococcus agalactiae/patogenicidad , Tilapia/microbiología
18.
Sci Rep ; 11(1): 540, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33436658

RESUMEN

Group B Streptococcus (GBS) is a major cause of neonatal morbidity and mortality. Serbia has not fully implemented preventive measures against GBS neonatal diseases. Therefore, we aimed to assess the maternal GBS colonisation and invasive neonatal disease rate, to reveal the trends of antimicrobial resistance and serotype distribution of GBS from various patient groups. Randomly selected non-invasive (n = 991) and all invasive GBS (n = 80) collected throughout Serbia from 2015 to 2020 were tested for antimicrobial susceptibility, capsular typing, and hvgA detection. Overall, 877/5621 (15.6%) pregnant women were colonised with GBS. Invasive GBS infections incidence in infants (0.18/1000 live births) showed a decreasing trend (0.3 to 0.1/1000 live births). Type III was overrepresented in infants with invasive infections (n = 35, 58.3%), whereas type V predominated among colonised adults (n = 224, 25.5%) and those with noninvasive (n = 37, 32.5%) and invasive infections (n = 8, 40%). The hypervirulent clone III/ST17 was highly associated with invasive infections (n = 28, 35%), particularly late-onset disease (n = 9, 47.4%), showing an increase from 12.3 to 14.8%. The GBS resistance to erythromycin and clindamycin was 26.7% and 22.1%, respectively, with an upward trend. The emergence of the hypervirulent clone III/ST17 and the escalation in GBS resistance highlight an urgent need for continuous monitoring of GBS infections.


Asunto(s)
Antibacterianos/farmacología , Enfermedades del Recién Nacido/microbiología , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/efectos de los fármacos , Clindamicina/farmacología , Farmacorresistencia Bacteriana/genética , Eritromicina/farmacología , Femenino , Humanos , Recién Nacido , Enfermedades del Recién Nacido/epidemiología , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/microbiología , Prevalencia , Serbia/epidemiología , Infecciones Estreptocócicas/epidemiología , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidad , Factores de Tiempo
19.
Braz J Microbiol ; 52(1): 303-310, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33398672

RESUMEN

Streptococcus agalactiae is a recognized pathogen associated with infections in neonates, elderly, and immunocompromised adults, particularly those with cancer. In the present investigation, clinical-epidemiological features, multidrug resistance profiles, and virulence genes of S. agalactiae strains isolated from cancer patients were investigated. S. agalactiae capsular distribution assays demonstrated that Ia (43.6%) and V (23.6%) types were predominantly detected among 55 clinical isolates tested; only one strain (GBS1428) was capsular type III/ST-17. The fbsB and hylB genes were detected in all isolates, while the iag, lmb, and fbsA genes were detected in 94.5%, 91%, and 91% of oncological isolates, respectively. The combination of PI-1 and PI-2a was the most common (60%) among S. agalactiae strains isolated from oncologic patients. S. agalactiae strains were resistant to tetracycline (85.5%), erythromycin (9%), and clindamycin (5.5%). Norfloxacin non-susceptible was detected in 7.3% of S. agalactiae strains. Our findings reinforce the need for S. agalactiae control measures in Brazil, including cancer patients.


Asunto(s)
Neoplasias/complicaciones , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/genética , Streptococcus agalactiae/aislamiento & purificación , Adolescente , Adulto , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Brasil/epidemiología , Farmacorresistencia Bacteriana Múltiple , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neoplasias/microbiología , Streptococcus agalactiae/efectos de los fármacos , Streptococcus agalactiae/patogenicidad , Factores de Virulencia/genética , Adulto Joven
20.
Int J Mol Sci ; 22(2)2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33477538

RESUMEN

The cell walls of Gram-positive bacteria contain a variety of glycopolymers (CWGPs), a significant proportion of which are covalently linked to the peptidoglycan (PGN) scaffolding structure. Prominent CWGPs include wall teichoic acids of Staphylococcus aureus, streptococcal capsules, mycobacterial arabinogalactan, and rhamnose-containing polysaccharides of lactic acid bacteria. CWGPs serve important roles in bacterial cellular functions, morphology, and virulence. Despite evident differences in composition, structure and underlaying biosynthesis pathways, the final ligation step of CWGPs to the PGN backbone involves a conserved class of enzymes-the LytR-CpsA-Psr (LCP) transferases. Typically, the enzymes are present in multiple copies displaying partly functional redundancy and/or preference for a distinct CWGP type. LCP enzymes require a lipid-phosphate-linked glycan precursor substrate and catalyse, with a certain degree of promiscuity, CWGP transfer to PGN of different maturation stages, according to in vitro evidence. The prototype attachment mode is that to the C6-OH of N-acetylmuramic acid residues via installation of a phosphodiester bond. In some cases, attachment proceeds to N-acetylglucosamine residues of PGN-in the case of the Streptococcus agalactiae capsule, even without involvement of a phosphate bond. A novel aspect of LCP enzymes concerns a predicted role in protein glycosylation in Actinomyces oris. Available crystal structures provide further insight into the catalytic mechanism of this biologically important class of enzymes, which are gaining attention as new targets for antibacterial drug discovery to counteract the emergence of multidrug resistant bacteria.


Asunto(s)
Proteínas Bacterianas/genética , Proteínas de Unión a las Penicilinas/genética , Peptidoglicano/genética , Factores de Transcripción/genética , Pared Celular/genética , Glicoproteínas/genética , Humanos , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidad , Especificidad por Sustrato , Ácidos Teicoicos/genética , Ácidos Teicoicos/metabolismo
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