scholarly journals Genomic inversion drives small colony variant formation and increased virulence inP. aeruginosa

2018 ◽  
Author(s):  
Sharon Irvine ◽  
Boyke Bunk ◽  
Hannah K. Bayes ◽  
Cathrin Sprӧer ◽  
James P. R. Connolly ◽  
...  
Keyword(s):  
Chronic Infection ◽  
Large Scale ◽  
Lung Infection ◽  
Phenotypic Change ◽  
Central Metabolism ◽  
Genetic Switch ◽  
Small Colony Variant ◽  
Transcriptional Changes ◽  
Small Colony ◽  
Variant Formation

AbstractPhenotypic change is a hallmark of bacterial adaptation during chronic infection. In the case of chronicPseudomonas aeruginosalung infection in patients with cystic fibrosis, well-characterised phenotypic variants include mucoid and small colony variants (SCVs). It has previously been shown that SCVs can be reproducibly isolated from the murine lung following the establishment of chronic infection with mucoidP. aeruginosastrain NH57388A. Here we show, using a combination of singlemolecule real-time (PacBio) and Illumina sequencing that the genetic switch for conversion to the SCV phenotype is a large genomic inversion through recombination between homologous regions of two rRNA operons. This phenotypic conversion is associated with large-scale transcriptional changes distributed throughout the genome. This global rewiring of the cellular transcriptomic output results in changes to normally differentially regulated genes that modulate resistance to oxidative stress, central metabolism and virulence. These changes are of clinical relevance since the appearance of SCVs during chronic infection is associated with declining lung function.

scholarly journals Phenotypic and Genotypic Characteristics of Small Colony Variants and Their Role in Chronic Infection

2015 ◽  
Vol 8 ◽  
pp. MBI.S25800 ◽  
Author(s):  
Benjamin E. Johns ◽  
Kevin J. Purdy ◽  
Nicholas P. Tucker ◽  
Sarah E. Maddocks
Keyword(s):  
Chronic Infection ◽  
Antimicrobial Treatment ◽  
Microbial Populations ◽  
Phenotypic Characteristics ◽  
Genetic Changes ◽  
Small Colony Variant ◽  
Small Colony ◽  
A Minor ◽  
Genotypic Characteristics ◽  
Slow Growing

Small colony variant (SCV) bacteria arise spontaneously within apparently homogeneous microbial populations, largely in response to environmental stresses, such as antimicrobial treatment. They display unique phenotypic characteristics conferred in part by heritable genetic changes. Characteristically slow growing, SCVs comprise a minor proportion of the population from which they arise but persist by virtue of their inherent resilience and host adaptability. Consequently, SCVs are problematic in chronic infection, where antimicrobial treatment is administered during the acute phase of infection but fails to eradicate SCVs, which remain within the host causing recurrent or chronic infection. This review discusses some of the phenotypic and genotypic changes that enable SCVs to successfully proliferate within the host environment as potential pathogens and strategies that could ameliorate the resolution of infection where SCVs are present.

scholarly journals YfiBNR Mediates Cyclic di-GMP Dependent Small Colony Variant Formation and Persistence in Pseudomonas aeruginosa

2010 ◽  
Vol 6 (3) ◽  
pp. e1000804 ◽  
Author(s):  
Jacob G. Malone ◽  
Tina Jaeger ◽  
Christian Spangler ◽  
Daniel Ritz ◽  
Anne Spang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Small Colony Variant ◽  
Small Colony ◽  
Variant Formation

scholarly journals Increased Expression of Clumping Factor and Fibronectin-Binding Proteins by hemB Mutants of Staphylococcus aureus Expressing Small Colony Variant Phenotypes

2002 ◽  
Vol 70 (10) ◽  
pp. 5428-5437 ◽  
Author(s):  
Pierre Vaudaux ◽  
Patrice Francois ◽  
Carmelo Bisognano ◽  
William L. Kelley ◽  
Daniel P. Lew ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Surface Display ◽  
Human Embryonic Kidney Cells ◽  
Small Colony Variant ◽  
Reverse Transcription Pcr ◽  
Bacterial Adhesins ◽  
Transport Chain ◽  
Complete Restoration ◽  
Small Colony ◽  
Slow Growing

ABSTRACT Small colony variants (SCVs) of Staphylococcus aureus are slow-growing subpopulations that cause persistent and relapsing infections. The altered phenotype of SCV can arise from defects in menadione or hemin biosynthesis, which disrupt the electron transport chain and decrease ATP concentrations. With SCVs, virulence is altered by a decrease in exotoxin production and susceptibility to various antibiotics, allowing their intracellular survival. The expression of bacterial adhesins by SCVs is poorly documented. We tested fibrinogen- and fibronectin-mediated adhesion of a hemB mutant of S. aureus 8325-4 that is defective for hemin biosynthesis and exhibits a complete SCV phenotype. In this strain, adhesion to fibrinogen and fibronectin was significantly higher than that of its isogenic, normally growing parent and correlated with the increased surface display of these adhesins as assessed by flow cytometry. Real-time quantitative reverse transcription-PCR demonstrated increased expression of clfA and fnb genes by the hemB mutant compared to its isogenic parent. The influence of the hemB mutation on altered adhesin expression was confirmed by showing complete restoration of the wild-type adhesive phenotype in the hemB mutant, either by complementing with intact hemB or by supplementing the growth medium with hemin. Increased surface display of fibrinogen and fibronectin adhesins by the hemB mutation occurred independently from agr, a major regulatory locus of virulence factors in S. aureus. Both agr-positive and agr-lacking hemB mutants were also more efficiently internalized by human embryonic kidney cells than were their isogenic controls, presumably because of increased surface display of their fibronectin adhesins.

SMALL COLONY VARIANT STAPHYLOCOCCUS AUREUS MULTIORGAN INFECTION

2007 ◽  
Vol 26 (3) ◽  
pp. 269-271 ◽  
Author(s):  
Hemant Agarwal ◽  
Rosemary Verrall ◽  
Sudha P. Singh ◽  
Yi-Wei Tang ◽  
Gregory Wilson
Keyword(s):  
Staphylococcus Aureus ◽  
Small Colony Variant ◽  
Small Colony

scholarly journals The Chlorite Dismutase (HemQ) fromStaphylococcus aureusHas a Redox-sensitive Heme and Is Associated with the Small Colony Variant Phenotype

2013 ◽  
Vol 288 (32) ◽  
pp. 23488-23504 ◽  
Author(s):  
Jeffrey A. Mayfield ◽  
Neal D. Hammer ◽  
Richard C. Kurker ◽  
Thomas K. Chen ◽  
Sunil Ojha ◽  
...  
Keyword(s):  
Chlorite Dismutase ◽  
Small Colony Variant ◽  
Variant Phenotype ◽  
Small Colony

scholarly journals A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly.

1997 ◽  
Vol 179 (15) ◽  
pp. 4706-4712 ◽  
Author(s):  
C von Eiff ◽  
C Heilmann ◽  
R A Proctor ◽  
C Woltz ◽  
G Peters ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Small Colony Variant ◽  
Small Colony ◽  
A Site
Sign in / Sign up

Export Citation Format

Share Document