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Role of small colony variants in persistence of Pseudomonas aeruginosa infections in cystic fibrosis lungs.

Malone JG - Infect Drug Resist (2015)

Bottom Line: The evolution of SCVs in the CF lung is associated with overproduction of the ubiquitous bacterial signaling molecule cyclic-di-GMP, with increased cyclic-di-GMP levels shown to be responsible for the SCV phenotype in a number of different CF lung isolates.Here, we review the current state of research in clinical P. aeruginosa SCVs.We will discuss the phenotypic characteristics underpinning the SCV morphotype, the clinical implications of lung colonization with SCVs, and the molecular basis and clinical evolution of the SCV phenotype in the CF lung environment.

View Article: PubMed Central - PubMed

Affiliation: John Innes Centre, Norwich, UK ; School of Biological Sciences, University of East Anglia, Norwich, UK.

ABSTRACT
Pseudomonas aeruginosa is an opportunistic pathogen that predominates during the later stages of cystic fibrosis (CF) lung infections. Over many years of chronic lung colonization, P. aeruginosa undergoes extensive adaptation to the lung environment, evolving both toward a persistent, low virulence state and simultaneously diversifying to produce a number of phenotypically distinct morphs. These lung-adapted P. aeruginosa strains include the small colony variants (SCVs), small, autoaggregative isolates that show enhanced biofilm formation, strong attachment to surfaces, and increased production of exopolysaccharides. Their appearance in the sputum of CF patients correlates with increased resistance to antibiotics, poor lung function, and prolonged persistence of infection, increasing their relevance as a subject for clinical investigation. The evolution of SCVs in the CF lung is associated with overproduction of the ubiquitous bacterial signaling molecule cyclic-di-GMP, with increased cyclic-di-GMP levels shown to be responsible for the SCV phenotype in a number of different CF lung isolates. Here, we review the current state of research in clinical P. aeruginosa SCVs. We will discuss the phenotypic characteristics underpinning the SCV morphotype, the clinical implications of lung colonization with SCVs, and the molecular basis and clinical evolution of the SCV phenotype in the CF lung environment.

No MeSH data available.


Related in: MedlinePlus

cdG signaling.Notes: cdG is produced from GTP by GGDEF proteins and degraded by EAL and HD-GYP phosphodiesterases. cdG binds to a variety of different receptors, suppressing motility and virulence and promoting EPS production, biofilm formation, and the SCV phenotype.Abbreviations: cdG, cyclic-di-GMP; EPS, extracellular polysaccharides; GTP, guanosine triphosphate; pGpG, 5′-phosphoguanylyl-(3′–5′)-guanosineguanosine; SCV, small colony variant.
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f2-idr-8-237: cdG signaling.Notes: cdG is produced from GTP by GGDEF proteins and degraded by EAL and HD-GYP phosphodiesterases. cdG binds to a variety of different receptors, suppressing motility and virulence and promoting EPS production, biofilm formation, and the SCV phenotype.Abbreviations: cdG, cyclic-di-GMP; EPS, extracellular polysaccharides; GTP, guanosine triphosphate; pGpG, 5′-phosphoguanylyl-(3′–5′)-guanosineguanosine; SCV, small colony variant.

Mentions: Following early indications from two independent research labs,21,22 strong evidence has accumulated for a causal link between the SCV phenotype and the bacterial second messenger cdG.12,25,40–42 cdG is a ubiquitous bacterial signaling molecule that controls a wide range of cellular processes involved in the transition between motile, virulent, and sessile biofilm forming lifestyles.43,44 The cyclic dinucleotide is produced from two molecules of GTP (guanosine triphosphate) by DGCs and degraded to pGpG (5′-phosphoguanylyl-(3′–5′)-guanosineguanosine) by phosphodiesterases;45 enzymes containing the conserved GGDEF and EAL/HD-GYP domains, respectively.46–49 In general, cdG production is associated with community behavior phenotypes such as EPS production and biofilm formation, while low cdG levels lead to enhanced motility, virulence, and a single-celled lifestyle43 (Figure 2). cdG signal transduction is a highly complex process, with many bacterial species containing dozens of different cdG-signaling proteins.43P. aeruginosa is no exception, with 33 predicted GGDEF and 17 EAL domain-containing proteins.50,51 These cdG metabolic enzymes control the intracellular level of cdG and hence regulate the expression of various phenotypic outputs. In P. aeruginosa, this includes exopolysaccharide production,52–54 production and deployment of proteinaceous adhesins,55,56 siderophore production,12 rhamnolipid biosynthesis,57 and virulence and cytotoxicity systems,51,58–60 as well as the assembly, function, and control of type IV pili61,62 and the bacterial flagellum.54,63–65


Role of small colony variants in persistence of Pseudomonas aeruginosa infections in cystic fibrosis lungs.

Malone JG - Infect Drug Resist (2015)

cdG signaling.Notes: cdG is produced from GTP by GGDEF proteins and degraded by EAL and HD-GYP phosphodiesterases. cdG binds to a variety of different receptors, suppressing motility and virulence and promoting EPS production, biofilm formation, and the SCV phenotype.Abbreviations: cdG, cyclic-di-GMP; EPS, extracellular polysaccharides; GTP, guanosine triphosphate; pGpG, 5′-phosphoguanylyl-(3′–5′)-guanosineguanosine; SCV, small colony variant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524453&req=5

f2-idr-8-237: cdG signaling.Notes: cdG is produced from GTP by GGDEF proteins and degraded by EAL and HD-GYP phosphodiesterases. cdG binds to a variety of different receptors, suppressing motility and virulence and promoting EPS production, biofilm formation, and the SCV phenotype.Abbreviations: cdG, cyclic-di-GMP; EPS, extracellular polysaccharides; GTP, guanosine triphosphate; pGpG, 5′-phosphoguanylyl-(3′–5′)-guanosineguanosine; SCV, small colony variant.
Mentions: Following early indications from two independent research labs,21,22 strong evidence has accumulated for a causal link between the SCV phenotype and the bacterial second messenger cdG.12,25,40–42 cdG is a ubiquitous bacterial signaling molecule that controls a wide range of cellular processes involved in the transition between motile, virulent, and sessile biofilm forming lifestyles.43,44 The cyclic dinucleotide is produced from two molecules of GTP (guanosine triphosphate) by DGCs and degraded to pGpG (5′-phosphoguanylyl-(3′–5′)-guanosineguanosine) by phosphodiesterases;45 enzymes containing the conserved GGDEF and EAL/HD-GYP domains, respectively.46–49 In general, cdG production is associated with community behavior phenotypes such as EPS production and biofilm formation, while low cdG levels lead to enhanced motility, virulence, and a single-celled lifestyle43 (Figure 2). cdG signal transduction is a highly complex process, with many bacterial species containing dozens of different cdG-signaling proteins.43P. aeruginosa is no exception, with 33 predicted GGDEF and 17 EAL domain-containing proteins.50,51 These cdG metabolic enzymes control the intracellular level of cdG and hence regulate the expression of various phenotypic outputs. In P. aeruginosa, this includes exopolysaccharide production,52–54 production and deployment of proteinaceous adhesins,55,56 siderophore production,12 rhamnolipid biosynthesis,57 and virulence and cytotoxicity systems,51,58–60 as well as the assembly, function, and control of type IV pili61,62 and the bacterial flagellum.54,63–65

Bottom Line: The evolution of SCVs in the CF lung is associated with overproduction of the ubiquitous bacterial signaling molecule cyclic-di-GMP, with increased cyclic-di-GMP levels shown to be responsible for the SCV phenotype in a number of different CF lung isolates.Here, we review the current state of research in clinical P. aeruginosa SCVs.We will discuss the phenotypic characteristics underpinning the SCV morphotype, the clinical implications of lung colonization with SCVs, and the molecular basis and clinical evolution of the SCV phenotype in the CF lung environment.

View Article: PubMed Central - PubMed

Affiliation: John Innes Centre, Norwich, UK ; School of Biological Sciences, University of East Anglia, Norwich, UK.

ABSTRACT
Pseudomonas aeruginosa is an opportunistic pathogen that predominates during the later stages of cystic fibrosis (CF) lung infections. Over many years of chronic lung colonization, P. aeruginosa undergoes extensive adaptation to the lung environment, evolving both toward a persistent, low virulence state and simultaneously diversifying to produce a number of phenotypically distinct morphs. These lung-adapted P. aeruginosa strains include the small colony variants (SCVs), small, autoaggregative isolates that show enhanced biofilm formation, strong attachment to surfaces, and increased production of exopolysaccharides. Their appearance in the sputum of CF patients correlates with increased resistance to antibiotics, poor lung function, and prolonged persistence of infection, increasing their relevance as a subject for clinical investigation. The evolution of SCVs in the CF lung is associated with overproduction of the ubiquitous bacterial signaling molecule cyclic-di-GMP, with increased cyclic-di-GMP levels shown to be responsible for the SCV phenotype in a number of different CF lung isolates. Here, we review the current state of research in clinical P. aeruginosa SCVs. We will discuss the phenotypic characteristics underpinning the SCV morphotype, the clinical implications of lung colonization with SCVs, and the molecular basis and clinical evolution of the SCV phenotype in the CF lung environment.

No MeSH data available.


Related in: MedlinePlus