Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Phage-mediated horizontal transfer of a Staphylococcus aureus virulence-associated genomic island.

ABSTRACT: Staphylococcus aureus is a major pathogen of humans and animals. The capacity of S. aureus to adapt to different host species and tissue types is strongly influenced by the acquisition of mobile genetic elements encoding determinants involved in niche adaptation. The genomic islands νSaα and νSaβ are found in almost all S. aureus strains and are characterized by extensive variation in virulence gene content. However the basis for the diversity and the mechanism underlying mobilization of the genomic islands between strains are unexplained. Here, we demonstrated that the genomic island, νSaβ, encoding an array of virulence factors including staphylococcal superantigens, proteases, and leukotoxins, in addition to bacteriocins, was transferrable in vitro to human and animal strains of multiple S. aureus clones via a resident prophage. The transfer of the νSaβ appears to have been accomplished by multiple conversions of transducing phage particles carrying overlapping segments of the νSaβ. Our findings solve a long-standing mystery regarding the diversification and spread of the genomic island νSaβ, highlighting the central role of bacteriophages in the pathogenic evolution of S. aureus.

SUBMITTER: Moon BY

PROVIDER: S-EPMC4402969 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Staphylococcus aureus temperate bacteriophage: carriage and horizontal gene transfer is lineage associated.

Project description:Staphylococcus aureus is a major cause of human and animal infections. Bacteriophage are a class of mobile genetic element (MGE) that carry virulence genes and disseminate them horizontally, including Panton-Valentine leukocidin (PVL), the immune evasion cluster (IEC) associated with human specificity, and enterotoxin A the major toxin associated with food poisoning. S. aureus isolates group into major clonal complex (CC) lineages that largely evolve independently due to possession of different restriction-modification (RM) systems. We aimed to better understand the horizontal and vertical transmission dynamics of virulence and resistance genes by bacteriophage by using (i) bioinformatic approaches to analyze bacteriophage genomes from the first 79 sequenced S. aureus isolates and (ii) S. aureus microarrays to analyze the distribution of bacteriophage and virulence genes in S. aureus isolates from a broader range of lineages. The distribution of eight bacteriophage families was highly variable but lineage associated. Nevertheless, there was evidence of frequent acquisition and loss and not just vertical transmission. Most bacteriophage genes were dispensable, and extensive mosaicism was seen. Surprisingly, virulence genes were tightly associated with specific phage families. This data suggests S. aureus bacteriophage evolve rapidly, and the horizontal gene transfer (HGT) of virulence genes encoded by bacteriophage is restricted by bacteriophage family and the lineage of the host bacterium, delaying the evolution of fully resistant and virulent strains.

| S-EPMC3417521 | biostudies-literature

Staphylococcus aureus virulence attenuation and immune clearance mediated by a phage lysin-derived protein.

Project description:New anti-infective approaches are much needed to control multi-drug-resistant (MDR) pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA). Here, we found for the first time that a recombinant protein derived from the cell wall binding domain (CBD) of the bacteriophage lysin PlyV12, designated as V12CBD, could attenuate S. aureus virulence and enhance host immune defenses via multiple manners. After binding with V12CBD, S. aureus became less invasive to epithelial cells and more susceptible to macrophage killing. The expressions of multiple important virulence genes of S. aureus were reduced 2.4- to 23.4-fold as response to V12CBD More significantly, V12CBD could activate macrophages through NF-?B pathway and enhance phagocytosis against S. aureus As a result, good protections of the mice from MRSA infections were achieved in therapeutic and prophylactic models. These unique functions of V12CBD would render it a novel alternative molecule to control MDRS. aureus infections.

| S-EPMC6120661 | biostudies-literature

Ecological Overlap and Horizontal Gene Transfer in Staphylococcus aureus and Staphylococcus epidermidis.

Project description:The opportunistic pathogens Staphylococcus aureus and Staphylococcus epidermidis represent major causes of severe nosocomial infection, and are associated with high levels of mortality and morbidity worldwide. These species are both common commensals on the human skin and in the nasal pharynx, but are genetically distinct, differing at 24% average nucleotide divergence in 1,478 core genes. To better understand the genome dynamics of these ecologically similar staphylococcal species, we carried out a comparative analysis of 324 S. aureus and S. epidermidis genomes, including 83 novel S. epidermidis sequences. A reference pan-genome approach and whole genome multilocus-sequence typing revealed that around half of the genome was shared between the species. Based on a BratNextGen analysis, homologous recombination was found to have impacted on 40% of the core genes in S. epidermidis, but on only 24% of the core genes in S. aureus. Homologous recombination between the species is rare, with a maximum of nine gene alleles shared between any two S. epidermidis and S. aureus isolates. In contrast, there was considerable interspecies admixture of mobile elements, in particular genes associated with the SaPIn1 pathogenicity island, metal detoxification, and the methicillin-resistance island SCCmec. Our data and analysis provide a context for considering the nature of recombinational boundaries between S. aureus and S. epidermidis and, the selective forces that influence realized recombination between these species.

| S-EPMC4453061 | biostudies-literature

Genetic variation among hospital isolates of methicillin-sensitive Staphylococcus aureus: evidence for horizontal transfer of virulence genes.

Project description:Staphylococcus aureus strains often carry in their genomes virulence genes that are not found in all strains and that may be carried on discrete genetic elements. Strains also differ in that they carry one of four classes of an accessory gene regulator (agr) locus, an operon that regulates virulence factor expression and that has been proposed to be a therapeutic target. To look at their distribution among hospital strains, we investigated 38 methicillin-sensitive S. aureus isolates, classifying the isolates by agr class and screening them for the presence and restriction fragment length polymorphisms (RFLPs) of 12 core and 14 accessory virulence genes. Twenty-three (61%) were agr class I, 10 (26%) were agr class II, and 5 (13%) were agr class III. None were agr class IV. The S. aureus strains had distinguishable RFLP profiles, although clusters of isolates with clearly related core gene profiles were found among our strains, including all five agr class III strains, two sets of six strains within agr class I, and six strains within agr class II. Within these clusters there was evidence of horizontal acquisition and/or loss of multiple accessory virulence genes. Furthermore, two isolates from the same patient were identical except for the presence of the sea gene, indicating that movement of mobile elements may occur in vivo. Several strong correlations with the carriage of virulence genes between strains were seen, including a positive correlation between tst and agr class III and negative correlations between tst and lukE-splB and between lukE-splB and seg-sei. This suggests that the core genome or the presence of accessory genetic elements within a strain may influence acquisition and loss of other elements encoding virulence genes.

| S-EPMC88236 | biostudies-literature

NarGHJI mediated virulence in Staphylococcus aureus

Project description:To investigate the function NarGHJI in the regulation of the expression of virulence factors, we constructed a narGHJI mutant by targeted deletion of narG in MRSA isolate USA300 LAC We then performed gene expression profiling analysis using data obtained from RNA-seq of of two different strains at early exponential (OD600 = 0.5).

2022-12-17 | GSE220798 | GEO

Extensive horizontal gene transfer during Staphylococcus aureus co-colonization in vivo.

Project description:Staphylococcus aureus is a commensal and major pathogen of humans and animals. Comparative genomics of S. aureus populations suggests that colonization of different host species is associated with carriage of mobile genetic elements (MGE), particularly bacteriophages and plasmids capable of encoding virulence, resistance, and immune evasion pathways. Antimicrobial-resistant S. aureus of livestock are a potential zoonotic threat to human health if they adapt to colonize humans efficiently. We utilized the technique of experimental evolution and co-colonized gnotobiotic piglets with both human- and pig-associated variants of the lineage clonal complex 398, and investigated growth and genetic changes over 16 days using whole genome sequencing. The human isolate survived co-colonization on piglets more efficiently than in vitro. During co-colonization, transfer of MGE from the pig to the human isolate was detected within 4 h. Extensive and repeated transfer of two bacteriophages and three plasmids resulted in colonization with isolates carrying a wide variety of mobilomes. Whole genome sequencing of progeny bacteria revealed no acquisition of core genome polymorphisms, highlighting the importance of MGE. Staphylococcus aureus bacteriophage recombination and integration into novel sites was detected experimentally for the first time. During colonization, clones coexisted and diversified rather than a single variant dominating. Unexpectedly, each piglet carried unique populations of bacterial variants, suggesting limited transmission of bacteria between piglets once colonized. Our data show that horizontal gene transfer occurs at very high frequency in vivo and significantly higher than that detectable in vitro.

| S-EPMC4224341 | biostudies-literature

Employing lytic phage-mediated horizontal gene transfer in Lactococcus lactis.

Project description:Lactococcus lactis is a lactic acid bacterium widely used as a starter culture in the manufacture of dairy products, especially a wide variety of cheeses. Improved industrial strains would help to manufacture better food products that can meet the industry's and consumer's demands with respect to e.g. quality, taste, texture and shelf life. Bacteriophage infection of L. lactis starter cultures represents one of the main causes of fermentation failure and consequent economic losses for the dairy industry. In this study, however, we aim at employing bacteriophages for beneficial purposes. We developed an experimental setup to assess whether phage-mediated horizontal gene transfer could be used to enhance the genetic characteristics of L. lactis strains in accordance with the European law regarding the use of genetically modified organisms (GMOs) in the food industry. Although we could not show the transfer of chromosomal DNA we did successfully transduce two dissimilar plasmids from L. lactis strain MG1363 to one of its derivatives employing three different lactococcal bacteriophages.

| S-EPMC7489543 | biostudies-literature

Staphylococcus aureus pathogenicity island DNA is packaged in particles composed of phage proteins.

Project description:Staphylococcus aureus pathogenicity islands (SaPIs) have an intimate relationship with temperate staphylococcal phages. During phage growth, SaPIs are induced to replicate and are efficiently encapsidated into special small phage heads commensurate with their size. We have analyzed by amino acid sequencing and mass spectrometry the protein composition of the specific SaPI particles. This has enabled identification of major capsid and tail proteins and a putative portal protein. As expected, all these proteins were phage encoded. Additionally, these analyses suggested the existence of a protein required for the formation of functional phage but not SaPI particles. Mutational analysis demonstrated that the phage proteins identified were involved only in the formation and possibly the function of SaPI or phage particles, having no role in other SaPI or phage functions.

| S-EPMC2293202 | biostudies-literature

Targeting MgrA-mediated virulence regulation in Staphylococcus aureus.

Project description:Increasing antibiotic resistance in human pathogens necessitates the development of new approaches against infections. Targeting virulence regulation at the transcriptional level represents a promising strategy yet to be explored. A global transcriptional regulator, MgrA in Staphylococcus aureus, was identified previously as a key virulence determinant. We have performed a fluorescence anisotropy (FA)-based high-throughput screen that identified 5, 5-methylenedisalicylic acid (MDSA), which blocks the DNA binding of MgrA. MDSA represses the expression of ?-toxin that is up-regulated by MgrA and activates the transcription of protein A, a gene down-regulated by MgrA. MDSA alters bacterial antibiotic susceptibilities via an MgrA-dependent pathway. A mouse model of infection indicated that MDSA could attenuate S. aureus virulence. This work is a rare demonstration of utilizing small molecules to block protein-DNA interaction, thus tuning important biological regulation at the transcriptional level.

| S-EPMC3163066 | biostudies-literature

Ciprofloxacin and trimethoprim cause phage induction and virulence modulation in Staphylococcus aureus.

Project description:In Staphylococcus aureus strains of human origin, phages which integrate into the chromosomal gene coding for beta-hemolysin (hlb) are widely distributed. Most of them encode accessory virulence determinants such as staphylokinase (sak) or enterotoxins. Here, we analyzed the effects of ciprofloxacin and trimethoprim on phage induction and expression of phage-encoded virulence factors by using isolates from patients with cystic fibrosis for which the induction of hlb-converting phages was demonstrated in vivo (C. Goerke, S. Matias y Papenberg, S. Dasbach, K. Dietz, R. Ziebach, B. C. Kahl, and C. Wolz, J. Infect. Dis. 189:724-734, 2004) as well as a phi13 lysogen of phage-cured strain 8325-4. Treatment of lysogens with subinhibitory concentrations of either antibiotic resulted in (i) delysogenization of strains resembling the isolates picked up after chronic lung infection and (ii) replication of phages in the bacterial host in a dose-dependent manner. Ciprofloxacin treatment resulted in enhanced recA transcription, indicating involvement of the SOS response in phage mobilization. Induction of phi13 was linked to elevated expression of the phage-encoded virulence gene sak, chiefly due to the activation of latent phage promoters. In summary, we could show the induction of hlb-converting phages and a subsequent virulence modulation of the host bacterium by ciprofloxacin and trimethoprim.

| S-EPMC1346766 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data