scholarly journals No Change, No Life? What We Know about Phase Variation in Staphylococcus aureus

2021 ◽  
Vol 9 (2) ◽  
pp. 244
Author(s):  
Vishal Gor ◽  
Ryosuke L. Ohniwa ◽  
Kazuya Morikawa
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
High Frequency ◽  
Direct Evidence ◽  
Bacterial Species ◽  
Phase Variation ◽  
Opportunistic Pathogen ◽  
Adaptation Strategy ◽  
Innate Immune ◽  
Epigenetic Mechanisms

Phase variation (PV) is a well-known phenomenon of high-frequency reversible gene-expression switching. PV arises from genetic and epigenetic mechanisms and confers a range of benefits to bacteria, constituting both an innate immune strategy to infection from bacteriophages as well as an adaptation strategy within an infected host. PV has been well-characterized in numerous bacterial species; however, there is limited direct evidence of PV in the human opportunistic pathogen Staphylococcus aureus. This review provides an overview of the mechanisms that generate PV and focuses on earlier and recent findings of PV in S. aureus, with a brief look at the future of the field.

scholarly journals Making the Most of the Host; Targeting the Autophagy Pathway Facilitates Staphylococcus aureus Intracellular Survival in Neutrophils

2021 ◽  
Vol 12 ◽  
Author(s):  
Emilio G. Vozza ◽  
Michelle E. Mulcahy ◽  
Rachel M. McLoughlin
Keyword(s):  
Staphylococcus Aureus ◽  
Therapeutic Potential ◽  
Systemic Infection ◽  
Opportunistic Pathogen ◽  
Intracellular Survival ◽  
Innate Immune ◽  
Pathogenic Role ◽  
New Host ◽  
Increased Risk ◽  
Autophagy Pathway

The success of Staphylococcus aureus as a human commensal and an opportunistic pathogen relies on its ability to adapt to several niches within the host. The innate immune response plays a key role in protecting the host against S. aureus infection; however, S. aureus adeptness at evading the innate immune system is indisputably evident. The “Trojan horse” theory has been postulated to describe a mechanism by which S. aureus takes advantage of phagocytes as a survival niche within the host to facilitate dissemination of S. aureus to secondary sites during systemic infection. Several studies have determined that S. aureus can parasitize both professional and non-professional phagocytes by manipulating the host autophagy pathway in order to create an intracellular survival niche. Neutrophils represent a critical cell type in S. aureus infection as demonstrated by the increased risk of infection among patients with congenital neutrophil disorders. However, S. aureus has been repeatedly shown to survive intracellularly within neutrophils with evidence now supporting a pathogenic role of host autophagy. By manipulating this pathway, S. aureus can also alter the apoptotic fate of the neutrophil and potentially skew other important signalling pathways for its own gain. Understanding these critical host-pathogen interactions could lead to the development of new host directed therapeutics for the treatment of S. aureus infection by removing its intracellular niche and restoring host bactericidal functions. This review discusses the current findings surrounding intracellular survival of S. aureus within neutrophils, the pathogenic role autophagy plays in this process and considers the therapeutic potential for targeting this immune evasion mechanism.

scholarly journals Formation of Staphylococcus aureus Biofilm in the Presence of Sublethal Concentrations of Disinfectants Studied via a Transcriptomic Analysis Using Transcriptome Sequencing (RNA-seq)

2017 ◽  
Vol 83 (24) ◽  
Author(s):  
M. Slany ◽  
J. Oppelt ◽  
L. Cincarova
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Transcriptome Sequencing ◽  
Expression Profiles ◽  
Bacterial Species ◽  
Rna Seq ◽  
Altered Expression ◽  
Content Type ◽  
Sublethal Concentrations

ABSTRACT Staphylococcus aureus is a common biofilm-forming pathogen. Low doses of disinfectants have previously been reported to promote biofilm formation and to increase virulence. The aim of this study was to use transcriptome sequencing (RNA-seq) analysis to investigate global transcriptional changes in S. aureus in response to sublethal concentrations of the commonly used food industry disinfectants ethanol (EtOH) and chloramine T (ChT) and their combination (EtOH_ChT) in order to better understand the effects of these agents on biofilm formation. Treatment with EtOH and EtOH_ChT resulted in more significantly altered expression profiles than treatment with ChT. Our results revealed that EtOH and EtOH_ChT treatments enhanced the expression of genes responsible for regulation of gene expression (sigB), cell surface factors (clfAB), adhesins (sdrDE), and capsular polysaccharides (cap8EFGL), resulting in more intact biofilm. In addition, in this study we were able to identify the pathways involved in the adaptation of S. aureus to the stress of ChT treatment. Further, EtOH suppressed the effect of ChT on gene expression when these agents were used together at sublethal concentrations. These data show that in the presence of sublethal concentrations of tested disinfectants, S. aureus cells trigger protective mechanisms and try to cope with them. IMPORTANCE So far, the effect of disinfectants is not satisfactorily explained. The presented data will allow a better understanding of the mode of disinfectant action with regard to biofilm formation and the ability of bacteria to survive the treatment. Such an understanding could contribute to the effort to eliminate possible sources of bacteria, making disinfectant application as efficient as possible. Biofilm formation plays significant role in the spread and pathogenesis of bacterial species.

scholarly journals Localized Reversible Frameshift Mutation in theflhA Gene Confers Phase Variability to Flagellin Gene Expression in Campylobacter coli

2000 ◽  
Vol 182 (1) ◽  
pp. 207-210 ◽  
Author(s):  
Simon F. Park ◽  
Desmond Purdy ◽  
Stephen Leach
Keyword(s):  
Gene Expression ◽  
High Frequency ◽  
Frameshift Mutation ◽  
Phase Variation ◽  
Campylobacter Coli ◽  
Coding Region ◽  
Generate Functional ◽  
Flagellin Gene ◽  
Homopolymeric Tract ◽  
Insertion And Deletion

ABSTRACT Phase variation of flagellin gene expression in Campylobacter coli UA585 was correlated with high-frequency, reversible insertion and deletion frameshift mutations in a short homopolymeric tract of thymine residues located in the N-terminal coding region of the flhA gene. Mutation-based phase variation inflhA may generate functional diversity in the host and environment.

scholarly journals Characterization and Comparative Analysis of the Staphylococcus aureus Genomic Island vSaβ: an In Silico Approach

2019 ◽  
Vol 201 (22) ◽  
Author(s):  
Anita J. Kläui ◽  
Renate Boss ◽  
Hans U. Graber
Keyword(s):  
Staphylococcus Aureus ◽  
In Silico ◽  
Serine Proteases ◽  
Genomic Island ◽  
Bacterial Species ◽  
Opportunistic Pathogen ◽  
Genomic Islands ◽  
Protease Gene ◽  
Sequencing Data ◽  
Content Type

ABSTRACT Staphylococcus aureus is a widespread opportunistic pathogen to humans and animals. Of its genome, 20 to 25% varies between strains and consists of phages, pathogenicity islands, transposons, and genomic islands. S. aureus harbors up to three genomic islands, vSaα, vSaβ, and vSaγ. The vSaβ region of S. aureus can encode a number of virulence-associated factors, such as serine proteases, leukocidins, enterotoxins, bacteriocins, or a hyaluronate lyase. In this study, the vSaβ regions of 103 clinically relevant S. aureus strains were characterized in silico and compared to the three predefined vSaβ types. We here suggest a superordinate system of 15 different vSaβ types, of which 12 were newly defined. Each vSaβ type has a distinct structure with a distinct set of genes, which are both highly conserved. Between the different types, gene content and composition vary substantially. Based on our data, a strain’s vSaβ type is strongly coupled with its clonal complex, suggesting that vSaβ was acquired in an ancestral S. aureus strain, arguably by phage mediation, before differentiation into clonal complexes. In addition, we addressed the issue of ambiguous nomenclature in the serine protease gene cluster and propose a novel, phylogeny-based nomenclature of the cluster contained in the vSaβ region. IMPORTANCE With the rapid increase of available sequencing data on clinically relevant bacterial species such as S. aureus, the genomic basis of clinical phenotypes can be investigated in much more detail, allowing a much deeper understanding of the mechanisms involved in disease. We characterized in detail the S. aureus genomic island vSaβ and defined a superordinate system to categorize S. aureus strains based on their vSaβ type, providing information about the strains’ virulence-associated genes and clinical potential.

scholarly journals Generation of Virulence Factor Variants in Staphylococcus aureus Biofilms

2007 ◽  
Vol 189 (22) ◽  
pp. 7961-7967 ◽  
Author(s):  
Jeremy M. Yarwood ◽  
Kara M. Paquette ◽  
Ilya B. Tikh ◽  
Esther M. Volper ◽  
E. Peter Greenberg
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Hemolytic Activity ◽  
Bacterial Species ◽  
Phase Variation ◽  
Accessory Gene ◽  
Altered Expression ◽  
Sensing System ◽  
Accessory Gene Regulator ◽  
Different Strains

ABSTRACT Several serious diseases are caused by biofilm-associated Staphylococcus aureus. Colonial variants occur in biofilms of other bacterial species, and S. aureus variants are frequently isolated from biofilm-associated infections. Thus, we studied the generation of variants with altered expression of virulence factors in S. aureus biofilms. We observed that the number of variants found in biofilms, as measured by hemolytic activity, varied for different strains. Further study of hemolytic activity and signaling by the accessory gene regulator (Agr) quorum-sensing system in one S. aureus strain revealed three primary biofilm subpopulations: nonhemolytic (Agr deficient), hemolytic (Agr positive), and hyperhemolytic (also Agr positive). The nonhemolytic variant became the numerically dominant subpopulation in the biofilm. The nonhemolytic variant phenotype was stable and heritable, indicating a genetic perturbation, whereas the hyperhemolytic phenotype was unstable, suggesting a phase variation. Transcription profiling revealed that expression of the agr locus and many extracellular virulence factors was repressed in the nonhemolytic variant. Expression of the agr-activating gene, sarU, was also repressed in the nonhemolytic variant, suggesting one potential regulatory pathway responsible for the Agr-deficient phenotype. We suggest that the development of these variants in biofilms may have important clinical implications.

scholarly journals Streptococcus pneumoniae TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Melissa B. Oliver ◽  
Ankita Basu Roy ◽  
Ranjit Kumar ◽  
Elliot J. Lefkowitz ◽  
W. Edward Swords
Keyword(s):  
Gene Expression ◽  
Recent Work ◽  
Bacterial Species ◽  
Phase Variation ◽  
Nasopharyngeal Colonization ◽  
Content Type ◽  
Bacterial Surface ◽  
Variable Expression ◽  
Dna Methylase ◽  
Single Allele

ABSTRACT A growing number of bacterial species undergo epigenetic phase variation due to variable expression or specificity of DNA-modifying enzymes. For pneumococci, this phase variation has long been appreciated as being revealed by changes in colony opacity, which are reflected in changes in expression or accessibility of factors on the bacterial surface. Recent work showed that recombination-generated variation in alleles of the HsdS DNA methylase specificity subunit mediated pneumococcal phase variation. We generated phase-locked populations of S. pneumoniae TIGR4 expressing a single nonvariant hsdS allele and observed significant differences in gene expression and virulence. These results highlight the importance of focused pathogenesis studies within specific phase types. Moreover, the generation of single-allele hsdS constructs will greatly facilitate such studies. Streptococcus pneumoniae (pneumococcus) is a leading human pathogen that can cause serious localized and invasive diseases. Pneumococci can undergo a spontaneous and reversible phase variation that is reflected in colony opacity and which allows the population to adapt to different host environments. Generally, transparent variants are adapted for nasopharyngeal colonization, whereas opaque variants are associated with invasive disease. In recent work, colony phase variation was shown to occur by means of recombination events to generate multiple alleles of the hsdS targeting domain of a DNA methylase complex, which mediates epigenetic changes in gene expression. A panel of isogenic strains were created in the well-studied S. pneumoniae TIGR4 background that are “locked” in the transparent (n = 4) or opaque (n = 2) colony phenotype. The strains had significant differences in colony size which were stable over multiple passages in vitro and in vivo. While there were no significant differences in adherence for the phase-locked mutant strains to immortalized epithelial cells, biofilm formation and viability were reduced for the opaque variants in static assays. Nasopharyngeal colonization was stable for all strains, but the mortality rates differed between them. Transcript profiling by transcriptome sequencing (RNA-seq) analyses revealed that the expression levels of certain virulence factors were increased in a phase-specific manner. As epigenetic regulation of phase variation (often referred to as "phasevarion") is emerging as a common theme for mucosal pathogens, these results serve as a model for future studies of host-pathogen interactions. IMPORTANCE A growing number of bacterial species undergo epigenetic phase variation due to variable expression or specificity of DNA-modifying enzymes. For pneumococci, this phase variation has long been appreciated as being revealed by changes in colony opacity, which are reflected in changes in expression or accessibility of factors on the bacterial surface. Recent work showed that recombination-generated variation in alleles of the HsdS DNA methylase specificity subunit mediated pneumococcal phase variation. We generated phase-locked populations of S. pneumoniae TIGR4 expressing a single nonvariant hsdS allele and observed significant differences in gene expression and virulence. These results highlight the importance of focused pathogenesis studies within specific phase types. Moreover, the generation of single-allele hsdS constructs will greatly facilitate such studies.

scholarly journals Distribution of Hyaluronidase-producing Staphylococcus aureus and Staphylococcus epidermidis Isolated from Palm Skin and Anterior Nares of Healthy Malaysian Adults

2020 ◽  
Vol 5 (1) ◽  
pp. 42
Author(s):  
Nabila Huda Abdul Halim ◽  
Nur Syarafina Mohd Zahir ◽  
Nor Munirah Mohd Amin ◽  
Hanani Ahmad Yusof @ Hanafi
Keyword(s):  
Staphylococcus Aureus ◽  
Hyaluronic Acid ◽  
Healthy Subject ◽  
Staphylococcus Epidermidis ◽  
Female Subject ◽  
Bacterial Species ◽  
Opportunistic Pathogen ◽  
Equal Proportion ◽  
Biochemical Tests ◽  
And Gender

Introduction: The distribution of Staphylococcus aureus and Staphylococcus epidermidis among Malaysian healthy adults and their capability to produce enzyme hyaluronidase are less reported. Hyaluronidase degrade hyaluronic acid in animal connective tissue and facilitate bacterial spreading in host body. This study aims to identify the distribution of both Staphylococci species in healthy subject, the hyaluronidase producer among the isolates and the association of the latter with site of isolation (palm skin and anterior nares) and gender ofthe host. Methods: A total of 108 swab samples were collected from anterior nares and palm of 54 healthy subjects. The bacteria were identified through microscopic and biochemical tests, before screened for hyaluronidase production using hyaluronic acid diffusion rapid plate method. Results: Total of 139 bacterial isolates were identified; 68 isolates are S. aureus, 63 S. epidermidis and 8 other bacterial species. Staphylococcus aureus was highly isolated from palm (57%) than anterior nares (47%). On the contrary for S. epidermidis was highly isolated from anterior nares (53%) than from palm skin (43%). Equal proportion was found for both species in male and female subject. A total of 77 (59%) isolates produced hyaluronidase; 55%are S. aureus and 45% are S. epidermidis. Hyaluronidase-producer isolates are equally found between anterior nares (56%) and palm skin (61%) or male (57%) and female subject (60%) regardless of Staphylococcal species. No significant value was recorded for any analysis. Conclusion: Capability of commensal S. aureus and S. epidermidis isolated from healthy subject to produce hyaluronidase may indicate their potential as opportunistic pathogen whenever the opportunity arises in any way.

scholarly journals Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Jakob Haaber ◽  
Cathrine Friberg ◽  
Mark McCreary ◽  
Richard Lin ◽  
Stanley N. Cohen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Treatment Failure ◽  
Drug Exposure ◽  
Bacterial Species ◽  
Sensitivity Testing ◽  
Genetic Changes ◽  
Clinical Prognosis ◽  
Gram Negative ◽  
Content Type

ABSTRACT  Resistance ofStaphylococcus aureusto beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA] strains). As colistin-induced vancomycin tolerance is reversible, it may not be detected by routine sensitivity testing and may be responsible for treatment failure at vancomycin doses expected to be clinically effective based on such routine testing.IMPORTANCE   Commonly, antibiotic resistance is associated with permanent genetic changes, such as point mutations or acquisition of resistance genes. We show that phenotypic resistance can arise where changes in gene expression result in tolerance to an antibiotic without any accompanying genetic changes. Specifically, methicillin-resistantStaphylococcus aureus(MRSA) behaves like vancomycin-intermediate S. aureus (VISA) upon exposure to colistin, which is currently used against infections by Gram-negative bacteria. Vancomycin is a last-resort drug for treatment of serious S. aureus infections, and VISA is associated with poor clinical prognosis. Phenotypic and reversible resistance will not be revealed by standard susceptibility testing and may underlie treatment failure.

scholarly journals Global Transcriptome Analysis of Staphylococcus aureus Biofilms in Response to Innate Immune Cells

2013 ◽  
Vol 81 (12) ◽  
pp. 4363-4376 ◽  
Author(s):  
Tyler D. Scherr ◽  
Christelle M. Roux ◽  
Mark L. Hanke ◽  
Amanda Angle ◽  
Paul M. Dunman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Expression Patterns ◽  
Immune Defense ◽  
Innate Immune ◽  
Gene Expression Patterns ◽  
Content Type ◽  
Affymetrix Microarrays

ABSTRACTThe potent phagocytic and microbicidal activities of neutrophils and macrophages are among the first lines of defense against bacterial infections. YetStaphylococcus aureusis often resistant to innate immune defense mechanisms, especially when organized as a biofilm. To investigate howS. aureusbiofilms respond to macrophages and neutrophils, gene expression patterns were profiled using Affymetrix microarrays. The addition of macrophages toS. aureusstatic biofilms led to a global suppression of the biofilm transcriptome with a wide variety of genes downregulated. Notably, genes involved in metabolism, cell wall synthesis/structure, and transcription/translation/replication were among the most highly downregulated, which was most dramatic at 1 h compared to 24 h following macrophage addition to biofilms. Unexpectedly, few genes were enhanced in biofilms after macrophage challenge. Unlike coculture with macrophages, coculture ofS. aureusstatic biofilms with neutrophils did not greatly influence the biofilm transcriptome. Collectively, these experiments demonstrate thatS. aureusbiofilms differentially modify their gene expression patterns depending on the leukocyte subset encountered.

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