A novel peptidoglycan <scp>D</scp>,<scp>L</scp>‐endopeptidase induced by <scp><i>S</i></scp><i>almonella</i> inside eukaryotic cells contributes to virulence

Rico-Pérez, Gadea; Pezza, Alejandro; Pucciarelli, M. Graciela; Pedro, Miguel A. de; Soncini, Fernando C.; Portillo, Francisco García‐del

doi:10.1111/mmi.13248

Cited by 24 publications

(41 citation statements)

References 49 publications

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“…Note the absence of reads in the RNA expression profile for ecgA (STM1940) in the LB medium-LSP and in low Mg 2+ medium, conditions in which the EcgA protein is produced (see also Rico-Perez et al). 12 In concordance with transcriptomic data obtained from intracellular S. Typhimurium isolated from fibroblasts 31 and the RNA-Seq data obtained in bacteria infecting macrophages, 10 EcgA protein levels increase notoriously in intracellular bacteria by a regulation mediated by the PhoP-PhoQ two-component system (see Rico-Perez et al) 12 .…”

Section: Rna-seq Applied To Both the Pathogen And The Hostsupporting

confidence: 69%

“…A remarkable example in S. Typhimurium is that involving the STM1940 (SL1344_1873) gene, renamed by us as ecgA, which encodes a peptidoglycan hydrolase. 12 The RNAseq data obtained in S. Typhimurium using infection-relevant conditions 8 and in intracellular bacteria 10 indicate that ecgA is a gene specifically up-regulated inside macrophages, with expression levels barely detected in any of the extracellular conditions tested (Fig. 1A).…”

Section: Rna-seq Provides New Insights Into the Regulatory Rna Landscapementioning

confidence: 99%

“…1B), ISM medium (Fig. 1C) and PCN medium at pH 5.8, 12 this latter is a medium used by Hinton and colleagues in the RNA-seq study covering infection-relevant conditions. 8 Moreover, production of EcgA protein by S. Typhimurium was also shown to respond to low magnesium concentrations, 12 a regulation that remained "invisible" at the RNA-seq data level (Fig.…”

Section: Rna-seq Provides New Insights Into the Regulatory Rna Landscapementioning

confidence: 99%

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RNA-Seq unveils new attributes of the heterogeneous Salmonella-host cell communication

Portillo

Pucciarelli

2017

RNA Biology

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High-throughput RNA sequencing (RNA-Seq) has uncovered hundreds of small RNAs and complex modes of RNA regulation in every bacterium analyzed to date. This complexity agrees with the adaptability of most bacteria to varied environments including, in the case of pathogens, the new niches encountered in the host. Recent RNA-Seq studies have analyzed simultaneously gene expression in the intracellular pathogen Salmonella enterica and infected host cells at population and single-cell level. Distinct polarization states or interferon responses in the infected macrophage were linked to variable growth rates or activities of defined virulence regulators in intra-phagosomal bacteria. Intracellular Salmonella, however, exhibit disparate intracellular lifestyles depending the host cell, ranging from a hyper-replicative cytosolic state in epithelial cells to a non-replicative intra-phagosomal condition in varied host cell types. The basis of such diverse pathogen-host communications could be examined by RNA-Seq studies in single intracellular Salmonella cells, certainly a challenge for future investigations.

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Section: Rna-seq Applied To Both the Pathogen And The Hostsupporting

confidence: 69%

Section: Rna-seq Provides New Insights Into the Regulatory Rna Landscapementioning

confidence: 99%

Section: Rna-seq Provides New Insights Into the Regulatory Rna Landscapementioning

confidence: 99%

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RNA-Seq unveils new attributes of the heterogeneous Salmonella-host cell communication

Portillo

Pucciarelli

2017

RNA Biology

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“…Prediction of CpxR-binding site. The consensus motif for the CpxR-binding site was generated by training the Multiple Expectation Maximization for motif Elicitation (MEME) tool (46) using as input cognate binding sequences in the promoter regions of the following CpxR-regulated genes from Salmonella: cpxP1, cpxP2, htrA, ppiA, yccA, spy, dsbA, amiA, amiC, cueP, gesA, and scsA (71)(72)(73)(74)(75). The obtained matrix was then submitted to the Find Individual Motif Occurrences (FIMO) tool to detect the presence of the motif in the promoter region of the prtA gene from S. marcescens (47).…”

Section: Methodsmentioning

confidence: 99%

CpxR-Dependent Thermoregulation of Serratia marcescens PrtA Metalloprotease Expression and Its Contribution to Bacterial Biofilm Formation

et al. 2018

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PrtA is the major secreted metalloprotease of Previous reports implicate PrtA in the pathogenic capacity of this bacterium. PrtA is also clinically used as a potent analgesic and anti-inflammatory drug, and its catalytic properties attract industrial interest. Comparatively, there is scarce knowledge about the mechanisms that physiologically govern PrtA expression in In this work, we demonstrate that PrtA production is derepressed when the bacterial growth temperature decreases from 37°C to 30°C. We show that this thermoregulation occurs at the transcriptional level. We determined that upstream of , there is a conserved motif that is directly recognized by the CpxR transcriptional regulator. This feature is found along strains irrespective of their isolation source, suggesting an evolutionary conservation of CpxR-dependent regulation of PrtA expression. We found that in s, the CpxAR system is more active at 37°C than at 30°C. In good agreement with these results, in a mutant background, is derepressed at 37°C, while overexpression of the NlpE lipoprotein, a well-known CpxAR-inducing condition, inhibits PrtA expression, suggesting that the levels of the activated form of CpxR are increased at 37°C over those at 30°C. In addition, we establish that PrtA is involved in the ability of to develop biofilm. In accordance, CpxR influences the biofilm phenotype only when bacteria are grown at 37°C. In sum, our findings shed light on regulatory mechanisms that fine-tune PrtA expression and reveal a novel role for PrtA in the lifestyle of We demonstrate that metalloprotease PrtA expression is transcriptionally thermoregulated. While strongly activated below 30°C, its expression is downregulated at 37°C. We found that in , the CpxAR signal transduction system, which responds to envelope stress and bacterial surface adhesion, is activated at 37°C and able to downregulate PrtA expression by direct interaction of CpxR with a binding motif located upstream of the gene. Moreover, we reveal that PrtA expression favors the ability of to develop biofilm, irrespective of the bacterial growth temperature. In this context, thermoregulation along with a highly conserved CpxR-dependent modulation mechanism gives clues about the relevance of PrtA as a factor implicated in the persistence of on abiotic surfaces and in bacterial host colonization capacity.

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“…PhoPQ is a global regulator and regulates a number of genes important in fitness and virulence (41)(42)(43). Again, further work is needed to investigate this.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine

Wand

Bock

Bonney

et al. 2017

Antimicrob Agents Chemother

228

218

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Klebsiella pneumoniae is an opportunistic pathogen that is often difficult to treat due to its multidrug resistance (MDR). We have previously shown that K. pneumoniae strains are able to "adapt" (become more resistant) to the widely used bisbiguanide antiseptic chlorhexidine. Here, we investigated the mechanisms responsible for and the phenotypic consequences of chlorhexidine adaptation, with particular reference to antibiotic cross-resistance. In five of six strains, adaptation to chlorhexidine also led to resistance to the last-resort antibiotic colistin. Here, we show that chlorhexidine adaptation is associated with mutations in the two-component regulator phoPQ and a putative Tet repressor gene (smvR) adjacent to the major facilitator superfamily (MFS) efflux pump gene, smvA. Upregulation of smvA (10-to 27-fold) was confirmed in smvR mutant strains, and this effect and the associated phenotype were suppressed when a wild-type copy of smvR was introduced on plasmid pACYC. Upregulation of phoPQ (5-to 15-fold) and phoPQ-regulated genes, pmrD (6-to 19-fold) and pmrK (18-to 64-fold), was confirmed in phoPQ mutant strains. In contrast, adaptation of K. pneumoniae to colistin did not result in increased chlorhexidine resistance despite the presence of mutations in phoQ and elevated phoPQ, pmrD, and pmrK transcript levels. Insertion of a plasmid containing phoPQ from chlorhexidine-adapted strains into wild-type K. pneumoniae resulted in elevated expression levels of phoPQ, pmrD, and pmrK and increased resistance to colistin, but not chlorhexidine. The potential risk of colistin resistance emerging in K. pneumoniae as a consequence of exposure to chlorhexidine has important clinical implications for infection prevention procedures.

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A novel peptidoglycan D,L‐endopeptidase induced by Salmonella inside eukaryotic cells contributes to virulence

Cited by 24 publications

References 49 publications

RNA-Seq unveils new attributes of the heterogeneous Salmonella-host cell communication

RNA-Seq unveils new attributes of the heterogeneous Salmonella-host cell communication

CpxR-Dependent Thermoregulation of Serratia marcescens PrtA Metalloprotease Expression and Its Contribution to Bacterial Biofilm Formation

Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine

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