scholarly journals The Phosphorylcholine Epitope Undergoes Phase Variation on a 43-Kilodalton Protein in Pseudomonas aeruginosa and on Pili of Neisseria meningitidis and Neisseria gonorrhoeae

1998 ◽  
Vol 66 (9) ◽  
pp. 4263-4267 ◽  
Author(s):  
Jeffrey N. Weiser ◽  
Joanna B. Goldberg ◽  
Nina Pan ◽  
Lynn Wilson ◽  
Mumtaz Virji
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Monoclonal Antibodies ◽  
Streptococcus Pneumoniae ◽  
Respiratory Tract ◽  
Neisseria Meningitidis ◽  
Phase Variation ◽  
Phase Variable ◽  
Human Respiratory Tract ◽  
Lower Growth ◽  
Gram Negative

ABSTRACT Phosphorylcholine (ChoP) is a component of the teichoic acids ofStreptococcus pneumoniae and has been recently identified on the lipopolysaccharide of Haemophilus influenzae, also a major pathogen of the human respiratory tract. Other gram-negative pathogens that frequently infect the human respiratory tract were surveyed for the presence of the ChoP epitope as indicated by binding to monoclonal antibodies (MAbs) recognizing this structure. The ChoP epitope was found on a 43-kDa protein on all clinical isolates ofPseudomonas aeruginosa examined and on several class I and II pili of Neisseria meningitidis. The specificity of the anti-ChoP MAb was demonstrated by the inhibition of binding in the presence of ChoP but not structural analogs. As in the case of H. influenzae, the expression of this epitope was phase variable on these species. In P. aeruginosa, this epitope was expressed at detectable levels only at lower growth temperatures. Expression of the ChoP epitope on piliated neisseriae displayed phase variation, both linked to pilus expression and independently of fully piliated bacteria.

scholarly journals Neuraminidase Expressed by Streptococcus pneumoniae Desialylates the Lipopolysaccharide of Neisseria meningitidis and Haemophilus influenzae: a Paradigm for Interbacterial Competition among Pathogens of the Human Respiratory Tract

2002 ◽  
Vol 70 (12) ◽  
pp. 7161-7164 ◽  
Author(s):  
Elizabeth A. Shakhnovich ◽  
Samantha J. King ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Sialic Acid ◽  
Respiratory Tract ◽  
Haemophilus Influenzae ◽  
Neisseria Meningitidis ◽  
Cell Surfaces ◽  
Human Respiratory Tract

ABSTRACT Both Neisseria meningitidis and Haemophilus influenzae are capable of mimicking host structures by decorating their lipopolysaccharides with sialic acid. We show that a neuraminidase expressed by Streptococcus pneumoniae (NanA) is able to desialylate the cell surfaces of both these species, which reside in and possibly compete for the same host niche.

scholarly journals 60 Contribution of nonfermenting Gram-negative bacilli (NFGNB) other than Pseudomonas aeruginosa (PA) in colonization of the respiratory tract in CF patients (pts)

2016 ◽  
Vol 15 ◽  
pp. S66-S67
Author(s):  
K. Semczuk ◽  
H. Dmeńska ◽  
K. Dzierżanowska-Fangrat ◽  
R. Kuthan ◽  
A. Wojcieszek ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Respiratory Tract ◽  
Gram Negative

scholarly journals Frequency and predictors of colonization of the respiratory tract by VIM-2-producing Pseudomonas aeruginosa in patients of a newly established intensive care unit

2006 ◽  
Vol 55 (10) ◽  
pp. 1435-1439 ◽  
Author(s):  
Maria Horianopoulou ◽  
Nicholas J. Legakis ◽  
Maria Kanellopoulou ◽  
Sotiris Lambropoulos ◽  
Athanassios Tsakris ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Pseudomonas Aeruginosa ◽  
Intensive Care ◽  
Respiratory Tract ◽  
Tertiary Care ◽  
Nucleotide Sequencing ◽  
Gram Negative Bacteria ◽  
Care Hospital ◽  
Gram Negative ◽  
Icu Stay

The aim of this study was to examine the frequency and predictors of colonization of the respiratory tract by metallo-β-lactamase (MBL)-producing Gram-negative bacteria in patients admitted to a newly established intensive care unit (ICU) of a tertiary care hospital. Specimens of tracheobronchial aspirates for microbiological studies were obtained every day for the first 3 days of the ICU stay and subsequently every third day for the rest of the ICU stay. PCR analysis and nucleotide sequencing were performed to identify bacteria that had MBL genes. Thirty-five patients (20 male, 15 female) were hospitalized during the initial 3 month period of functioning of the ICU. Colonization of the lower respiratory tract by Gram-negative bacteria was found in 29 of 35 patients (83 %) during the first 6–20 days (median 13 days) following admission to the ICU (13 patients with Acinetobacter baumannii, ten with Pseudomonas aeruginosa, three with Enterobacter aerogenes, two with Klebsiella pneumoniae and one with Stenotrophomonas maltophilia). Six of 29 patients (21 %) colonized with Gram-negative bacteria had bla VIM-2-positive P. aeruginosa isolates; one of these patients developed clinical infection due to this micro-organism. Previous use of carbapenems (P=0.01) or other β-lactams (P=0.03), as well as a stay in the ICU of >20 days (P<0.001), were associated with colonization with bla VIM-2-producing P. aeruginosa. In conclusion, colonization by Gram-negative bacteria of the respiratory tract of patients in this newly established ICU was common (83 %). Use of β-lactams, including carbapenems, was associated with subsequent colonization of the respiratory tract with MBL-positive P. aeruginosa.

Effect of ximedone on the state of humoral antibacterial immunity in patients with angina

1998 ◽  
Vol 79 (5) ◽  
pp. 354-358
Author(s):  
O. D. Zinkevich ◽  
I. E. Kravchenko ◽  
V. K. Fazylov ◽  
N. A. Safina ◽  
O. A. Platonov ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Candida Albicans ◽  
Streptococcus Pneumoniae ◽  
Streptococcus Pyogenes ◽  
Proteus Mirabilis ◽  
The State ◽  
Analysis Method ◽  
High Concentration ◽  
Gram Negative

The concentration of antibodies to antigens Streptococcus pyogenes, li posaccharide E of the salt 0 14, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Candida albicans, Streptococcus pneumoniae as well as to endotoxin (glycolipid RE 595 S.Minnesota) of Gram negative flora in patients with angina in the treatment dynamics is determined by the hardphase immunofermental analysis method. The data obtained show the low concentration of antibodies to staphylococcus, endotoxin of Gram negative flora, Candida and the high concentration to Pseudomonas aeryginosa for the whole time of observation. The changes revealed show the dysbalance in specific humoral immunity in patients with angina. The new drug ximedone normalizes the state of humoral antibacterial immunity in patients with angina.

scholarly journals Synergistic Activity of Mobile Genetic Element Defences in Streptococcus pneumoniae

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 707 ◽  
Author(s):  
Min Jung Kwun ◽  
Marco R. Oggioni ◽  
Stephen D. Bentley ◽  
Christophe Fraser ◽  
Nicholas J. Croucher
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mobile Genetic Element ◽  
Horizontal Transmission ◽  
Phase Variation ◽  
Uninfected Cell ◽  
Synergistic Activity ◽  
Phase Variable ◽  
Two Phase ◽  
Strain Transformation ◽  
Restriction Modification

A diverse set of mobile genetic elements (MGEs) transmit between Streptococcus pneumoniae cells, but many isolates remain uninfected. The best-characterised defences against horizontal transmission of MGEs are restriction-modification systems (RMSs), of which there are two phase-variable examples in S. pneumoniae. Additionally, the transformation machinery has been proposed to limit vertical transmission of chromosomally integrated MGEs. This work describes how these mechanisms can act in concert. Experimental data demonstrate RMS phase variation occurs at a sub-maximal rate. Simulations suggest this may be optimal if MGEs are sometimes vertically inherited, as it reduces the probability that an infected cell will switch between RMS variants while the MGE is invading the population, and thereby undermine the restriction barrier. Such vertically inherited MGEs can be deleted by transformation. The lack of between-strain transformation hotspots at known prophage att sites suggests transformation cannot remove an MGE from a strain in which it is fixed. However, simulations confirmed that transformation was nevertheless effective at preventing the spread of MGEs into a previously uninfected cell population, if a recombination barrier existed between co-colonising strains. Further simulations combining these effects of phase variable RMSs and transformation found they synergistically inhibited MGEs spreading, through limiting both vertical and horizontal transmission.

scholarly journals Phase Variation of NadA in Invasive Neisseria meningitidis Isolates Impacts on Coverage Estimates for 4C-MenB, a MenB Vaccine

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Luke R. Green ◽  
Jay Lucidarme ◽  
Neelam Dave ◽  
Hannah Chan ◽  
Stephen Clark ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
High Throughput ◽  
Meningococcal Disease ◽  
Regulatory Region ◽  
Phase Variation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Phase Variable ◽  
Content Type ◽  
Protective Antigens ◽  
Low Expression

ABSTRACT A recombinant NadA protein is one of the four major protective antigens of 4C-MenB (Bexsero), a vaccine developed for serogroup B Neisseria meningitidis (MenB). The meningococcal antigen typing system (MATS) is utilized as a high-throughput assay for assessing the invasive MenB strain coverage of 4C-MenB. Where present, the nadA gene is subject to phase-variable changes in transcription due to a 5′TAAA repeat tract located in a regulatory region. The promoter-containing intergenic region (IGR) sequences and 5′TAAA repeat numbers were determined for 906 invasive meningococcal disease isolates possessing the nadA gene. Exclusion of the 5′TAAA repeats reduced the number of IGR alleles from 82 to 23. Repeat numbers were associated with low and high levels of NadA expression by Western blotting and enzyme-linked immunosorbent assay (ELISA). Low-expression repeat numbers were present in 83% of 179 MenB isolates with NadA-2/3 or NadA-1 peptide variants and 68% of 480 MenW ST-11 complex isolates with NadA-2/3 peptide variants. For isolates with vaccine-compatible NadA variants, 93% of MATS-negative isolates were associated with low-expression repeat numbers, whereas 63% of isolates with MATS relative potency (RP) scores above the 95% confidence interval for the positive bactericidal threshold had high-expression repeat numbers. Analysis of 5′TAAA repeat numbers has potential as a rapid, high-throughput method for assessing strain coverage for the NadA component of 4C-MenB. A key application will be assessing coverage in meningococcal disease cases where confirmation is by PCR only and MATS cannot be applied.

scholarly journals Genotypic and Phenotypic Characterization of theO-Linked Protein Glycosylation System Reveals High Glycan Diversity in Paired Meningococcal Carriage Isolates

2018 ◽  
Vol 200 (16) ◽  
Author(s):  
Bente Børud ◽  
Guro K. Bårnes ◽  
Ola Brønstad Brynildsrud ◽  
Elisabeth Fritzsønn ◽  
Dominique A. Caugant
Keyword(s):  
Neisseria Meningitidis ◽  
Phase Variation ◽  
Protein Glycosylation ◽  
Phase Variable ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Variable Expression ◽  
Evolutionary Forces ◽  
Strain Collection

ABSTRACTSpecies within the genusNeisseriadisplay significant glycan diversity associated with theO-linked protein glycosylation (pgl) systems due to phase variation and polymorphic genes and gene content. The aim of this study was to examine in detail thepglgenotype and glycosylation phenotype in meningococcal isolates and the changes occurring during short-term asymptomatic carriage. Paired meningococcal isolates derived from 50 asymptomatic meningococcal carriers, taken about 2 months apart, were analyzed with whole-genome sequencing. TheO-linked protein glycosylation genes were characterized in detail using the Genome Comparator tool at the https://pubmlst.org/ database. Immunoblotting with glycan-specific antibodies (Abs) was used to investigate the protein glycosylation phenotype. All majorpgllocus polymorphisms identified inNeisseria meningitidisto date were present in our isolate collection, with the variable presence ofpglGandpglH, both in combination with eitherpglBorpglB2. We identified significant changes and diversity in thepglgenotype and/or glycan phenotype in 96% of the paired isolates. There was also a high degree of glycan microheterogeneity, in which different variants of glycan structures were found at a given glycoprotein. The main mechanism responsible for the observed differences was phase-variable expression of the involved glycosyltransferases and theO-acetyltransferase. To our knowledge, this is the first characterization of thepglgenotype and glycosylation phenotype in a larger strain collection. This report thus provides important insight into glycan diversity inN. meningitidisand into the phase variability changes that influence the expressed glycoform repertoire during meningococcal carriage.IMPORTANCEBacterial meningitis is a serious global health problem, and one of the major causative organisms isNeisseria meningitidis, which is also a common commensal in the upper respiratory tract of healthy humans. In bacteria, numerous loci involved in biosynthesis of surface-exposed antigenic structures that are involved in the interaction between bacteria and host are frequently subjected to homologous recombination and phase variation. These mechanisms are well described inNeisseria, and phase variation provides the ability to change these structures reversibly in response to the environment. Protein glycosylation systems are becoming widely identified in bacteria, and yet little is known about the mechanisms and evolutionary forces influencing glycan composition during carriage and disease.

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

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
John M. Atack ◽  
Christopher J. Day ◽  
Jessica Poole ◽  
Kenneth L. Brockman ◽  
Jamie R. L. Timms ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Respiratory Tract ◽  
Binding Affinity ◽  
Binding Activity ◽  
Binding Domain ◽  
Dual Function ◽  
Affinity Binding ◽  
Phase Variable ◽  
Human Respiratory Tract ◽  
Human Airway

ABSTRACT 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. The remaining 75% of strains express HMW1/2. Previous work has shown that the HMW1 and HMW2 proteins mediate binding to 2-3- and 2-6-linked sialic acid glycans found in the human respiratory tract. Here, we show that the high-affinity binding domain of Hia, binding domain 1 (BD1), is responsible for binding to α2-6-sialyllactosamine (2-6 SLN) glycans. BD1 is highly specific for glycans that incorporate the form of sialic acid expressed by humans, N-acetylneuraminic acid (Neu5Ac). We further show that Hia has lower-affinity binding activity for 2-3-linked sialic acid and that this binding activity is mediated via a distinct domain. Thus, Hia with its dual binding activities functionally mimics the combined activities of the HMW1 and HMW2 adhesins. In addition, we show that Hia has a role in biofilm formation by strains of NTHi that express the adhesin. Knowledge of the binding affinity of this major NTHi adhesin and putative vaccine candidate will direct and inform development of future vaccines and therapeutic strategies for this important pathogen. IMPORTANCE Host-adapted bacterial pathogens like NTHi have evolved specific mechanisms to colonize their restricted host niche. Relatively few of the adhesins expressed by NTHi have been characterized as regards their binding affinity at the molecular level. In this work, we show that the major NTHi adhesin Hia preferentially binds to Neu5Ac-α2-6-sialyllactosamine, the form of sialic acid expressed in humans. The receptors targeted by Hia in the human airway mirror those targeted by influenza A virus and indicates the broad importance of sialic acid glycans as receptors for microbes that colonize the human airway.

scholarly journals Cellular and molecular biology of Neisseria meningitidis colonization and invasive disease

2010 ◽  
Vol 118 (9) ◽  
pp. 547-564 ◽  
Author(s):  
Darryl J. Hill ◽  
Natalie J. Griffiths ◽  
Elena Borodina ◽  
Mumtaz Virji
Keyword(s):  
Respiratory Tract ◽  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
Antigenic Variation ◽  
Rapid Onset ◽  
Host Cells ◽  
Bacterial Survival ◽  
Human Respiratory Tract ◽  
Adhesive Proteins

The human species is the only natural host of Neisseria meningitidis, an important cause of bacterial meningitis globally, and, despite its association with devastating diseases, N. meningitidis is a commensal organism found frequently in the respiratory tract of healthy individuals. To date, antibiotic resistance is relatively uncommon in N. meningitidis isolates but, due to the rapid onset of disease in susceptible hosts, the mortality rate remains approx. 10%. Additionally, patients who survive meningococcal disease often endure numerous debilitating sequelae. N. meningitidis strains are classified primarily into serogroups based on the type of polysaccharide capsule expressed. In total, 13 serogroups have been described; however, the majority of disease is caused by strains belonging to one of only five serogroups. Although vaccines have been developed against some of these, a universal meningococcal vaccine remains a challenge due to successful immune evasion strategies of the organism, including mimicry of host structures as well as frequent antigenic variation. N. meningitidis express a range of virulence factors including capsular polysaccharide, lipopolysaccharide and a number of surface-expressed adhesive proteins. Variation of these surface structures is necessary for meningococci to evade killing by host defence mechanisms. Nonetheless, adhesion to host cells and tissues needs to be maintained to enable colonization and ensure bacterial survival in the niche. The aims of the present review are to provide a brief outline of meningococcal carriage, disease and burden to society. With this background, we discuss several bacterial strategies that may enable its survival in the human respiratory tract during colonization and in the blood during infection. We also examine several known meningococcal adhesion mechanisms and conclude with a section on the potential processes that may operate in vivo as meningococci progress from the respiratory niche through the blood to reach the central nervous system.

scholarly journals Influence of the combination and phase variation status of the haemoglobin receptors HmbR and HpuAB on meningococcal virulence

Microbiology ◽  
2011 ◽  
Vol 157 (5) ◽  
pp. 1446-1456 ◽  
Author(s):  
Isfahan Tauseef ◽  
Odile B. Harrison ◽  
Karl G. Wooldridge ◽  
Ian M. Feavers ◽  
Keith R. Neal ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Meningococcal Disease ◽  
Systemic Disease ◽  
Phase Variation ◽  
Phase Variable ◽  
Insertion Element ◽  
Systemic Spread ◽  
High Level ◽  
Complete Deletion

Neisseria meningitidis can utilize haem, haemoglobin and haemoglobin–haptoglobin complexes as sources of iron via two TonB-dependent phase variable haemoglobin receptors, HmbR and HpuAB. HmbR is over-represented in disease isolates, suggesting a link between haemoglobin acquisition and meningococcal disease. This study compared the distribution of HpuAB and phase variation (PV) status of both receptors in disease and carriage isolates. Meningococcal disease (n = 214) and carriage (n = 305) isolates representative of multiple clonal complexes (CCs) were investigated for the distribution, polyG tract lengths and ON/OFF status of both haemoglobin receptors, and for the deletion mechanism for HpuAB. Strains with both receptors or only hmbR were present at similar frequencies among meningococcal disease isolates as compared with carriage isolates. However, >90 % of isolates from the three CCs CC5, CC8 and CC11 with the highest disease to carriage ratios contained both receptors. Strains with an hpuAB-only phenotype were under-represented among disease isolates, suggesting selection against this receptor during systemic disease, possibly due to the receptor having a high level of immunogenicity or being inefficient in acquisition of iron during systemic spread. Absence of hpuAB resulted from either complete deletion or replacement by an insertion element. In an examination of PV status, one or both receptors were found in an ON state in 91 % of disease and 71 % of carriage isolates. We suggest that expression of a haemoglobin receptor, either HmbR or HpuAB, is of major importance for systemic spread of meningococci, and that the presence of both receptors contributes to virulence in some strains.

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