Microbial Primer: Phase variation - survival and adaptability by generation of a diverse population.

Phase variation is defined as the rapid and reversible switching of gene expression, and typically occurs in genes encoding surface features in small genome bacterial pathogens. Phase variation has evolved to provide an extra survival mechanism in bacteria that lack multiple 'sense-and-respond' gene regulation systems. Many bacterial pathogens also encode DNA methyltransferases that are phase-variable, controlling systems called 'phasevarions' (phase-variable regulons).

Phasevarions in biogroup control expression of multiple proteins.

biogroup is a human-adapted pathogen and the causative agent of Brazilian purpuric fever (BPF), an invasive disease with high mortality, that sporadically manifests in children previously suffering conjunctivitis. Phase variation is a rapid and reversible switching of gene expression found in many bacterial species, and typically associated with outer-membrane proteins. Phase variation of cytoplasmic DNA methyltransferases has been shown to play important roles in bacterial gene regulation and can act as epigenetic switches, regulating the expression of multiple genes as part of systems called phasevarions (phase-variable regulons).

High-depth RNA-Seq data sets to investigate the differences in gene expression mediated by phasevarions in non-typeable .

Non-typeable (NTHi) is a major bacterial pathogen of the human airway. We report high-depth coverage RNA-Seq data from prototype NTHi strains 723 and R2866, encoding two of the most common phase-variable ModA alleles found in NTHi strains, ModA2 and ModA10, respectively.

Uncovering the link between the restriction modification system and LuxS in meningitis isolates.

is capable of randomly switching their genomic DNA methylation pattern between six distinct bacterial subpopulations (A-F) via recombination of a type 1 restriction-modification locus, . These pneumococcal subpopulations exhibit phenotypic changes which favor carriage or invasive disease. In particular, the allele has been associated with increased nasopharyngeal carriage and the downregulation of the gene.

Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions.

Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase-variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases.

Adherence of Nontypeable Haemophilus influenzae to Cells and Substrates of the Airway Is Differentially Regulated by Individual ModA Phasevarions.

Adherence of nontypeable Haemophilus influenzae (NTHi) to the host airway is an essential initial step for asymptomatic colonization of the nasopharynx, as well as development of disease. NTHi relies on strict regulation of multiple adhesins for adherence to host substrates encountered in the airway. NTHi encode a phase-variable cytoplasmic DNA methyltransferase, ModA, that regulates expression of multiple genes; a phasevarion (phase-variable regulon).

Examination of phase-variable haemoglobin-haptoglobin binding proteins in non-typeable Haemophilus influenzae reveals a diverse distribution of multiple variants.

Non-typeable Haemophilus influenzae (NTHi) is a major human pathogen for which there is no globally licensed vaccine. NTHi has a strict growth requirement for iron and encodes several systems to scavenge elemental iron and heme from the host. An effective NTHi vaccine would target conserved, essential surface factors, such as those involved in iron acquisition.

Pneumococcal Phasevarions Control Multiple Virulence Traits, Including Vaccine Candidate Expression.

Streptococcus pneumoniae is the most common cause of bacterial illness worldwide. Current vaccines based on the polysaccharide capsule are only effective against a limited number of the >100 capsular serotypes. A universal vaccine based on conserved protein antigens requires a thorough understanding of gene expression in S.

How bacteria utilize sialic acid during interactions with the host: snip, snatch, dispatch, match and attach.

-glycolylneuraminic acid (Neu5Gc), and its precursor -acetylneuraminic acid (Neu5Ac), commonly referred to as sialic acids, are two of the most common glycans found in mammals. Humans carry a mutation in the enzyme that converts Neu5Ac into Neu5Gc, and as such, expression of Neu5Ac can be thought of as a 'human specific' trait. Bacteria can utilize sialic acids as a carbon and energy source and have evolved multiple ways to take up sialic acids.

Complete Genome Sequences of Seven Neisseria gonorrhoeae Clinical Isolates from Mucosal and Disseminated Gonococcal Infections.

Neisseria gonorrhoeae is a Gram-negative bacterium that causes the sexually transmitted infection gonorrhea. N. gonorrhoeae has progressively developed resistance to all currently prescribed antibiotics, and no vaccine is available.

Complete Genome Sequence of Serogroup B Neisseria meningitidis Strain C311.

Neisseria meningitidis strain C311 has been widely used to study meningococcal pathogenesis in the past 30 years, but its genome is not available. Here, we report that the complete C311 genome is 2,311,508 bp in length, contains a total of 2,274 genes, and has a GC content of 51.25%.

The Autotransporter Adhesin Ata Recognizes Host Glycans as High-Affinity Receptors.

is a significant opportunistic pathogen responsible for infections of the lung, blood, skin, urinary tract, and soft tissues, with some strains exhibiting almost complete resistance to commonly used antibiotics. This multidrug resistance, together with a dearth of new antibiotic development, mean novel methods of treatment and prevention are urgently needed. Although many factors required to colonize the host have been identified, little is known about the specific host molecules recognized by these factors.

Streptococcus suis pathogenesis-A diverse array of virulence factors for a zoonotic lifestyle.

Streptococcus suis is a major cause of respiratory tract and invasive infections in pigs and is responsible for a substantial disease burden in the pig industry. S. suis is also a significant cause of bacterial meningitis in humans, particularly in South East Asia.

Actinobacillus pleuropneumoniae: The molecular determinants of virulence and pathogenesis.

Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, is responsible for high economic losses in swine herds across the globe. Pleuropneumonia is characterized by severe respiratory distress and high mortality. The knowledge about the interaction between bacterium and host within the porcine respiratory tract has improved significantly in recent years.

The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors.

NTHi is a human-adapted pathogen that colonizes the human respiratory tract. Strains of NTHi express multiple adhesins; however, there is a unique, mutually exclusive relationship between the major adhesins Hia and HMW1 and HMW2 (HMW1/2). Approximately 25% of NTHi strains express Hia, a phase-variable autotransporter protein that has a critical role in colonization of the host nasopharynx.

Systematic Analysis of REBASE Identifies Numerous Type I Restriction-Modification Systems with Duplicated, Distinct Specificity Genes That Can Switch System Specificity by Recombination.

-Adenine DNA methyltransferases associated with some Type I and Type III restriction-modification (R-M) systems are able to undergo phase variation, randomly switching expression ON or OFF by varying the length of locus-encoded simple sequence repeats (SSRs). This variation of methyltransferase expression results in genome-wide methylation differences and global changes in gene expression. These epigenetic regulatory systems are called phasevarions, phase-variable regulons, and are widespread in bacteria.

Epigenetic Regulation of Virulence and Immunoevasion by Phase-Variable Restriction-Modification Systems in Bacterial Pathogens.

Human-adapted bacterial pathogens use a mechanism called phase variation to randomly switch the expression of individual genes to generate a phenotypically diverse population to adapt to challenges within and between human hosts. There are increasing reports of restriction-modification systems that exhibit phase-variable expression. The outcome of phase variation of these systems is global changes in DNA methylation.

Moraxella catarrhalis phase-variable loci show differences in expression during conditions relevant to disease.

Moraxella catarrhalis is a human-adapted, opportunistic bacterial pathogen of the respiratory mucosa. Although asymptomatic colonization of the nasopharynx is common, M. catarrhalis can ascend into the middle ear, where it is a prevalent causative agent of otitis media in children, or enter the lower respiratory tract, where it is associated with acute exacerbations of chronic obstructive pulmonary disease in adults.

All major cholesterol-dependent cytolysins use glycans as cellular receptors.

Cholesterol-dependent cytolysins (CDCs) form pores in cholesterol-rich membranes, but cholesterol alone is insufficient to explain their cell and host tropism. Here, we show that all eight major CDCs have high-affinity lectin activity that identifies glycans as candidate cellular receptors. Streptolysin O, vaginolysin, and perfringolysin O bind multiple glycans, while pneumolysin, lectinolysin, and listeriolysin O recognize a single glycan class.

Transcriptomic Data Sets To Determine Gene Expression Changes Mediated by the Presence of PBT2 in Growth Medium of Multidrug-Resistant Neisseria gonorrhoeae WHO Z.

causes the sexually transmitted infection gonorrhea. High-coverage (∼3,300-fold) transcriptome sequencing data have been collected from multidrug-resistant strain WHO Z grown in the presence and absence of PBT2.

Transcriptome RNA Sequencing Data Set of Gene Expression in Moraxella catarrhalis On- and Off-Phase Variants of the Type III DNA Methyltransferase ModM3.

is a leading bacterial cause of otitis media and exacerbations of chronic obstructive pulmonary disease. Here, we announce a transcriptome RNA sequencing data set detailing global gene expression in two CCRI-195ME variants with expression of the DNA methyltransferase ModM3 phase varied either on or off.

Proteome of a Moraxella catarrhalis Strain under Iron-Restricted Conditions.

is a leading cause of otitis media and exacerbations of chronic obstructive pulmonary disease; however, its response to iron starvation during infection is not completely understood. Here, we announce a sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) data set describing the differential expression of the CCRI-195ME proteome under iron-restricted versus iron-replete conditions.