Regulation of virulence and antibiotic resistance by two-component regulatory systems in<i>Pseudomonas aeruginosa</i>

Gooderham, W. James; Hancock, Robert E. W.

doi:10.1111/j.1574-6976.2008.00135.x

Cited by 292 publications

(288 citation statements)

References 115 publications

(161 reference statements)

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“…This result is to be expected because the synthesis of EPS is a stationaryphase, gene-dependent process and the GacS/GacA TCS has been shown to regulate the expression of multiple phenotypes, including the production of virulence factors, A. Tahrioui, E. Quesada and I. Llamas enzymes, antibiotics and polymers (Gooderham & Hancock, 2009). This regulation may take place directly, as it does in Azotobacter vinelandii, with GacA activating the synthesis of polymers, alginate and poly-b-hydroxybutyrate (PHB) by regulating the expression of rpoS, which in turn controls stationary-phase functions (Castañeda et al, 2000(Castañeda et al, , 2001Hernandez-Eligio et al, 2011).…”

Section: Discussionmentioning

confidence: 96%

“…Among TCSs the GacS/GacA system is well preserved in a variety of Gram-negative bacterial genera, such as Acinetobacter, Azotobacter, Erwinia, Escherichia, Legionella, Pseudomonas, Salmonella, Serratia and Vibrio. The GacS/GacA TCS has been reported to regulate an array of phenotypes such as the production of virulence factors, plant-growth promotion, swarming motility, biofilm formation, exopolysaccharide (EPS) biosynthesis, production of secondary metabolites and quorum sensing (QS) signal molecules and the secretion of proteins and enzymes (Gooderham & Hancock, 2009;Heeb & Haas, 2001). …”

Section: Introductionmentioning

confidence: 99%

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Genetic and phenotypic analysis of the GacS/GacA system in the moderate halophile Halomonas anticariensis

2013

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A multisensory, hybrid histidine kinase (HK) and a response regulator (RR), which together may well constitute a two-component regulatory system (TCS), have been located in Halomonas anticariensis FP35 T by transposon mutagenesis. This TCS is homologous to the GacS/GacA system described for many Gram-negative bacteria. An analysis of crude N-acylhomoserine lactone (AHL) extracts from cultures of FP35gacS and FP35gacA mutants showed that they produced lower quantities of AHLs than the wild-type strain. In addition, RT-PCR analysis revealed a considerable decrease in the expression of the quorum-sensing (QS) genes hanR and hanI compared with the wild-type strain. This result indicates that the GacS/GacA TCS exerts a positive effect upon the QS HanR/HanI system and suggests its integral involvement in the intercellular communication strategies of this bacterium. We have also demonstrated the influence of GacS and GacA upon exopolysaccharide production and biofilm formation, in which this regulatory machinery appears to play a key role in an overall system that co-ordinates gene expression and behaviour in H. anticariensis FP35 T in response to environmental conditions.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Genetic and phenotypic analysis of the GacS/GacA system in the moderate halophile Halomonas anticariensis

2013

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“…We have shown that LpxOdependent lipid A modification is not only important for Klebsiella survival in the lung but also mediates resistance to the clinically relevant AP colistin. The connection between virulence and antibiotic resistance has been particularly studied in the case of Pseudomonas (40,41). A number of bacterial regulatory genes have been identified to influence both virulence and antibiotic resistance including PhoPQ (40,41).…”

Section: Discussionmentioning

confidence: 99%

Deciphering tissue-induced Klebsiella pneumoniae lipid A structure

Llobet

Martínez-Moliner

Moranta

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

134

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The outcome of an infection depends on host recognition of the pathogen, hence leading to the activation of signaling pathways controlling defense responses. A long-held belief is that the modification of the lipid A moiety of the lipopolysaccharide could help Gram-negative pathogens to evade innate immunity. However, direct evidence that this happens in vivo is lacking. Here we report the lipid A expressed in the tissues of infected mice by the human pathogen Klebsiella pneumoniae. Our findings demonstrate that Klebsiella remodels its lipid A in a tissue-dependent manner. Lipid A species found in the lungs are consistent with a 2-hydroxyacyl-modified lipid A dependent on the PhoPQ-regulated oxygenase LpxO. The in vivo lipid A pattern is lost in minimally passaged bacteria isolated from the tissues. LpxO-dependent modification reduces the activation of inflammatory responses and mediates resistance to antimicrobial peptides. An lpxO mutant is attenuated in vivo thereby highlighting the importance of this lipid A modification in Klebsiella infection biology. Colistin, one of the last options to treat multidrug-resistant Klebsiella infections, triggers the in vivo lipid A pattern. Moreover, colistin-resistant isolates already express the in vivo lipid A pattern. In these isolates, LpxO-dependent lipid A modification mediates resistance to colistin. Deciphering the lipid A expressed in vivo opens the possibility of designing novel therapeutics targeting the enzymes responsible for the in vivo lipid A pattern.

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“…They consist of a sensor histidine kinase and a transcriptional activator (Gooderham & Hancock, 2009;Rodrigue et al, 2000). PhoP-PhoQ is one such two-component regulatory system, which has been identified as important for virulence in several Enterobacteriaciae but has yet to be linked to virulence in P. aeruginosa.…”

Section: Introductionmentioning

confidence: 99%

The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa

et al. 2009

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Pseudomonas aeruginosa is a ubiquitous environmental Gram-negative bacterium that is also a major opportunistic human pathogen in nosocomial infections and cystic fibrosis chronic lung infections. PhoP-PhoQ is a two-component regulatory system that has been identified as essential for virulence and cationic antimicrobial peptide resistance in several other Gram-negative bacteria. This study demonstrated that mutation of phoQ caused reduced twitching motility, biofilm formation and rapid attachment to surfaces, 2.2-fold reduced cytotoxicity to human lung epithelial cells, substantially reduced lettuce leaf virulence, and a major, 10 000-fold reduction in competitiveness in chronic rat lung infections. Microarray analysis revealed that PhoQ controlled the expression of many genes consistent with these phenotypes and with its known role in polymyxin B resistance. It was also demonstrated that PhoQ controls the expression of many genes outside the known PhoP regulon.

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Regulation of virulence and antibiotic resistance by two-component regulatory systems inPseudomonas aeruginosa

Cited by 292 publications

References 115 publications

Genetic and phenotypic analysis of the GacS/GacA system in the moderate halophile Halomonas anticariensis

Genetic and phenotypic analysis of the GacS/GacA system in the moderate halophile Halomonas anticariensis

Deciphering tissue-induced Klebsiella pneumoniae lipid A structure

The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa

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